Perianal injectable bulking agents as treatment for faecal incontinence in adults

  • Conclusions changed
  • Review
  • Intervention

Authors


Abstract

Background

Faecal incontinence is a complex and distressing condition with significant medical and social implications. Injection of perianal bulking agents has been used to treat the symptoms of passive faecal incontinence. However, various agents have been used without a standardised technique and the supposed benefit of the treatment is largely anecdotal with a limited clinical research base.

Objectives

To determine the effectiveness of perianal injection of bulking agents for the treatment of faecal incontinence in adults.

Search methods

We searched the Cochrane Incontinence Group Specialised Register of trials (25 May 2012), ZETOC (3 May 2012), clinical trials registries (3 May 2012) and the reference lists of relevant articles.

Selection criteria

All randomised or quasi-randomised controlled trials comparing the use of injectable bulking agents for faecal incontinence with any alternative treatments or placebo were reviewed to evaluate the therapeutic effects. Case-control and cohort studies were also reviewed to assess risks and complications associated with the treatments.

Data collection and analysis

Two review authors (YM and CN) assessed the methodological quality of eligible trials and independently extracted data from the included trials using a range of pre-specified outcome measures.

Main results

Five eligible randomised trials with a total of 382 patients were identified. Four of the trials were at an uncertain or high risk of bias.

Most trials reported a short term benefit from injections regardless of the material used, including placebo saline injection. One study demonstrated dextranomer in stabilised hyaluronic acid (NASHA Dx) to be more effective than sham injection but with more adverse effects. Dextranomer in stabilised hyaluronic acid (NASHA Dx) was better than sham injections at six months (65/136, 48% versus 48/70, 69% participants not improved, defined as less than 50% reduction in incontinence episodes, RR 0.70, 95% CI 0.55 to 0.88; with more incontinence free days (3.1 days compared with 1.7 in the sham treatment group, MD 1.40 days, 95% CI 0.33 to 2.47). Another study comparing silicone material (PTQ™) to saline injections was too small to demonstrate a clinical benefit compared to the control injection of normal saline.

A silicone biomaterial (PTQ™) was shown to provide some advantages and was safer in treating faecal incontinence than carbon-coated beads (Durasphere®) in the short term.

Similarly, there were short term benefits from injections delivered under ultrasound guidance compared with digital guidance.

No long term evidence on outcomes was available and further conclusions were not warranted from the available data. None of the studies reported patient evaluation of outcomes and thus it is difficult to gauge whether the improvement in incontinence scores matched practical symptom improvements that mattered to the patients.

Authors' conclusions

One large randomised controlled trial has shown that this form of treatment using dextranomer in stabilised hyaluronic acid (NASHA Dx) improves continence for a little over half of patients in the short term. However, the number of identified trials was limited and most had methodological weaknesses.

Résumé scientifique

Injection périanale d'agents gonflants comme traitement de l'incontinence fécale chez l'adulte

Contexte

L'incontinence fécale est une maladie complexe et pénible aux implications médicales et sociales importantes. L'injection périanale d'agents gonflants est utilisée pour traiter les symptômes de l'incontinence fécale passive. Toutefois, différents agents ont été utilisés sans qu'il y ait une technique standardisée ; le bénéfice supposé du traitement est essentiellement de l'ordre du ouï dire et la base de recherche clinique est limitée.

Objectifs

Déterminer l'efficacité de l'injection périanale d'agents gonflants pour le traitement de l'incontinence fécale chez l'adulte.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre spécialisé d'essais cliniques du groupe Cochrane sur l’incontinence (25 mai 2012), ainsi que dans des registres d'essais cliniques et dans les références bibliographiques d'articles pertinents.

Critères de sélection

Tous les essais randomisés ou quasi-randomisés ayant comparé l'utilisation d'agents gonflants injectables pour l'incontinence fécale à d'autres traitements ou à un placebo ont été examinés afin d'évaluer les effets thérapeutiques. Des études cas-témoin et de cohorte ont également été examinées pour évaluer les risques et les complications associés aux traitements.

Recueil et analyse des données

Deux auteurs de la revue (YM et CN) ont évalué la qualité méthodologique des essais éligibles et ont extrait indépendamment les données des essais inclus en utilisant une série de mesures de résultat prédéfinies.

Résultats principaux

Cinq essais randomisés éligibles ont été identifiés, totalisant 382 patients. Quatre de ces essais étaient à risque incertain ou élevé de biais.

La plupart des essais avaient rendu compte d'un bénéfice à court terme des injections quel que soit le matériau utilisé, y compris l'injection de placebo salin. Une étude avait démontré que le dextranomère dans de l'acide hyaluronique stabilisé (NASHA Dx) était plus efficace que l'injection simulée, mais avec plus d'effets indésirables. Le dextranomère dans de l'acide hyaluronique stabilisé (NASHA Dx) était supérieur aux injections simulées après six mois (pour 65/136, 48% versus 48/70, 69 % des participants il n'y avait pas eu d'amélioration, c.-à-d. que la réduction des épisodes d'incontinence était de moins de 50%, RR 0,70 , IC à 95% 0,55 à 0,88), avec plus de jours sans incontinence (3,1 jours versus 1,7 dans le groupe à traitement simulé, DM 1,40 jours, IC à 95% 0,33 à 2,47). Une autre étude ayant comparé un matériau de silicone (PTQ™) aux injections de solution saline était de trop petite taille pour mettre en évidence un bénéfice clinique.

Un biomatériau de silicone (PTQ™) s'est avéré présenter certains avantages et était plus sûr à court terme pour le traitement de l'incontinence fécale que les billes revêtues de carbone (Durasphere®).

Il y avait de même des bénéfices à court terme de l'injection sous contrôle échographique par rapport au guidage digital.

Il n'y avait aucun élément probant sur des résultats à long terme, et les données disponibles ne permettent pas d'autres conclusions. Aucune des études n'avait rendu compte d'une évaluation des résultats par les patients et il est donc difficile d'apprécier si l'amélioration des scores d'incontinence correspond à une amélioration des symptômes pratiques qui sont importants pour les patients.

Conclusions des auteurs

Un grand essai contrôlé randomisé a montré que ce type de traitement au moyen de dextranomère dans de l'acide hyaluronique stabilisé (NASHA Dx) améliore à court terme la continence chez un peu plus de la moitié des patients. Le nombre d'essais identifiés était toutefois limité et la plupart présentaient des faiblesses méthodologiques.

Resumo

Injeção perianal de agentes de enchimento no tratamento de incontinência fecal de adultos.

Introdução

Incontinência fecal é uma condição complexa e angustiante com implicações médicas e sociais significativas. A injecção perianal de agentes de enchimento tem sido utilizada para tratar os sintomas passivos da incontinência fecal. No entanto, várias substâncias têm sido utilizadas sem uma técnica padronizada e o suposto benefício do tratamento é em grande parte anedótico, com uma base de investigação clínica limitada.

Objetivos

Determinar a efetividade da injeção perianal de agentes de enchimento no tratamento da incontinência fecal em adultos.

Métodos de busca

Nós procuramos os registros na Cochrane Incontinence Group Specialised Register of trials (25 de maio de 2012), ZETOC (3 de maio de 2012), registros de ensaios clínicos (3 de maio de 2012) e a lista de referências relevantes dos artigos.

Critério de seleção

Todos os ensaios clínicos randomizados ou quase-randomizados comparando o uso de agentes de enchimento injetáveis na incontinência fecal com qualquer tratamento alternativo ou placebo foram revisados para avaliar os efeitos terapêuticos. Estudos de caso-controle e de coorte também foram revisados para investigar os riscos e complicações associadas a estes tratamentos.

Coleta dos dados e análises

Dois revisores (YM e CN) avaliaram a qualidade metodológica dos ensaios clínicos elegíveis e independentemente extraíram os dados dos ensaios clínicos incluídos, utilizando uma variedade de medidas de desfecho pré-especificadas.

Principais resultados

Foram identificados cinco ensaios clínicos randomizados elegíveis, totalizando 382 pacientes. Quatro dos ensaios clínicos estavam em um risco incerto ou alto de viés.

A maioria dos ensaios clínicos relatou um benefício a curto prazo das injeções, independentemente do material utilizado, incluindo a injeção de solução salina placebo. Um estudo demonstrou que a injeção do dextranômero em ácido hialurónico estabilizado (NASHA Dx) é mais eficaz do que injeção simulada, mas com mais efeitos adversos. Dextranômero em ácido hialurónico estabilizado (NASHA Dx) foi melhor do que as injeções simuladas em seis meses (65/136, 48% versus 48/70, 69% de participantes que não melhoraram, definida como uma redução inferior a 50% em episódios de incontinência, RR de 0,70, 95 IC% 0,55-0,88; com mais de incontinência dias livres (3,1 dias em comparação com 1,7 no grupo de tratamento placebo, MD 1,40 dias, IC 95% 0,33-2,47). Outro estudo que comparou a injeção de um material de silicone (PTQ ™) com injeções de soro fisiológico era muito pequeno para demonstrar um benefício clínico em comparação com a de injeção controle de solução salina.

Um biomaterial de silicone (PTQ ™) demonstrou que pode ter algumas vantagens e ser mais seguro no tratamento da incontinência fecal do que partículas revestidas de carbono (Durasphere ®) à curto prazo.

Da mesma forma, houve benefícios a curto prazo de injeções guiadas por ultrassom em comparação com a guida pelo dedo.

Nenhuma evidência de resultados à longo prazo estava disponível e outras conclusões não eram justificadas com base nos dados disponíveis. Nenhum dos estudos relatou avaliação dos resultados pelos pacientes e, portanto, é difícil avaliar se a melhora do escore de incontinência corresponde a melhora prática dos sintomas que importavam para os pacientes.

Conclusão dos autores

Um grande ensaio clínico randomizado mostrou que esta forma de tratamento usando dextranômero em ácido hialurônico estabilizado (NASHA Dx) melhora a continência em pouco mais da metade dos pacientes à curto prazo. No entanto, o número de ensaios clínicos identificados foi limitado e a maioria tinha deficiências metodológicas.

Notas de tradução

Traduzido por: Pedro Luiz Toledo de Arruda Lourencao, Unidade de Medicina Baseada em Evidências da Unesp, Brazil Contato: portuguese.ebm.unit@gmail.com

アブストラクト

成人の便失禁治療における肛門周囲への充填剤注入

背景

便失禁は、医学的にも社会的にも大きな影響をもたらす複雑でつらい症状である。肛門周囲への充填剤の注入は、漏出性便失禁の治療に用いられている。しかし、さまざまな充填剤が標準化技術なしに使用されており、治療で想定される利益は、大部分が個々の症例の限定的な臨床研究に基づいている。

目的

成人における便失禁の治療に対する、肛門周囲への充填剤注入の有効性を検討すること。

検索戦略

the Cochrane Incontinence Group Specialised Register of trials(2012年5月25日)、ZETOC(2012年5月3日)、clinical trials registries(2012年5月3日)、および関連性のある論文の参考文献リストを検索した。

選択基準

便失禁に対する注入充填剤の使用と、あらゆる代替療法またはプラセボを比較したすべてのランダム化比較試験(RCT)、または準ランダム化比較試験を調査し、治療効果を評価した。また、ケースコントロール研究とコホート研究を調査し、本療法に関連するリスクと合併症を評価した。

データ収集と分析

2名のレビューア(YMとCN)が適格な試験について方法論的な質を評価し、事前に定めたさまざまなアウトカム指標を用いて、選択した試験から独立してデータを抽出した。

主な結果

合計382例を対象とした5件の適格なRCTを同定した。バイアスについては、このうち4件で不明または高リスクであった。

大部分の試験では、プラセボである生理食塩水など、注入された物質にかかわらず、注入による短期的な利益を報告した。1件の研究では、安定化ヒアルロン酸ナトリウムデキストラノマー(NASHA Dx)は偽治療よりも有効であるが、より多くの有害作用がみられることが明らかになった。NASHA Dxは6カ月時点で偽治療よりも良好であった。改善しなかった参加者の割合はNASHA Dx 群で48%(65/136)であったのに対し、偽治療群では69%(48/70)であった。NASHA Dx 群では、失禁エピソードの減少が50%未満(RR 0.70、95%CI 0.55~0.88)で、失禁しない日が偽治療群より多く、NASHA Dx 群では3.1日であったのに対し偽治療群では1.7日であった(平均差(MD)1.40日、95%CI 0.33~2.47))。シリコン物質(PTQ™)と生理食塩水の注入を比較した別の研究は小規模であったため、通常の生理食塩水を注入したコントロールと比較して臨床的な利益を実証することが出来なかった。

シリコン生体適合物質(PTQ™)は有効であることが示されており、便失禁の治療において、炭素被覆ビーズ(Durasphere®)よりも短期的には安全であった。

同様に、デジタル誘導と比較して超音波誘導下の注入は短期的に有効であった。

アウトカムに関する長期的なエビデンスが得られておらず、利用できるデータからさらなる結論を出すことは妥当ではなかった。アウトカムに関する患者の評価を報告した研究はなかったため、失禁スコアの改善が、患者にとって重要な実際の症状の改善と同等であるかを判断するのは難しい。

著者の結論

1件の大規模なRCTでは、安定化ヒアルロン酸ナトリウムデキストラノマー(NASHA Dx)を用いる治療法が、半数をやや上回る患者で短期的に排便抑制能力を改善することを示した。しかし、同定した試験数に限りがあり、また、大部分の試験に方法論的な脆弱性があった。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.7.11]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Injection of bulking material around the anus (back passage) for the treatment of faecal incontinence in adults

Loss of bowel control, also known as faecal incontinence, can be a devastating problem. It affects men and women of all ages in up to 15% of the adult population. Faecal incontinence can radically affect everyday life as many people become almost house bound, being unable to undertake simple tasks, such as shopping, because they are worried about faecal leakage.

Faecal incontinence may be due to a problem with the two muscles around the anus (back passage). These muscles can be damaged or become weak due to injury during child birth or operations to treat anal conditions such as haemorrhoids (piles) and fistulas (abnormal channels between the skin and back passage). The anal muscles then become unable to hold back the stools until the person reaches the toilet. The inner ring or internal anal sphincter muscle normally keeps the anus closed at all times except when opening the bowel, preventing passive leakage of stool. A treatment has been developed to treat faecal incontinence, which involves injecting a substance into or near this muscle to make it bulkier so that the anus closes better. It has been advocated as a simple and safe option.

In this review, one large trial demonstrated that injection of dextranomer stabilised in hyaluronic acid improves the symptoms of incontinence in the short term in little over half of those who received the treatment. The other four trials reviewed were of limited value because they were generally poor in methodological quality and small in size. There are no reported long term results for this treatment.

Résumé simplifié

Injection d'un matériau gonflant autour de l'anus pour le traitement de l'incontinence fécale chez l'adulte

La perte de contrôle de la défécation, appelée aussi incontinence fécale, peut être un problème terrible. Elle affecte des hommes et des femmes de tous âges jusqu'à représenter 15% de la population adulte. L'incontinence fécale peut affecter radicalement la vie quotidienne, car beaucoup de personnes ne peuvent quasiment plus quitter la maison et deviennent incapables d'exécuter des tâches simples, telles que faire des courses, par crainte de fuites fécales.

L'incontinence fécale peut être due à un problème au niveau des deux muscles entourant l'anus. Ces muscles peuvent être endommagés ou s'affaiblir en raison d'une blessure à l'accouchement ou d'opérations pour le traitement d'affections anales telles que les hémorroïdes et les fistules (communications anormales entre la peau et l'anus). Les muscles de l'anus deviennent alors incapables de retenir les selles jusqu'à ce que la personne atteigne les toilettes. La bague interne ou muscle du sphincter anal interne maintient normalement l'anus fermé en permanence sauf lors de la défécation, empêchant ainsi la fuite passive de selles. Un traitement a été développé pour l'incontinence fécale, qui consiste à injecter une substance dans ou à proximité de ce muscle pour le rendre plus volumineux afin que l'anus soit mieux fermé. Il a été préconisé en tant qu'option simple et sûre.

Dans cette revue, un essai à grande échelle avait montré que l'injection de dextranomère stabilisé dans de l'acide hyaluronique améliore les symptômes de l'incontinence à court terme chez un peu plus de la moitié de ceux ayant reçu le traitement. Les quatre autres essais examinés étaient d'une utilité limitée parce qu'ils étaient généralement de qualité méthodologique médiocre et de petite taille. Aucun résultat à long terme de ce traitement n'avait été rapporté.

Notes de traduction

Traduit par: French Cochrane Centre 1st March, 2013
Traduction financée par: Pour la France : Ministère de la Santé. Pour le Canada : Instituts de recherche en santé du Canada, ministère de la Santé du Québec, Fonds de recherche de Québec-Santé et Institut national d'excellence en santé et en services sociaux.

Resumo para leigos

Injeção de substâncias de enchimento ao redor do ânus para o tratamento na incontinência fecal em adultos.

Perda do controle intestinal, também conhecida como incontinência fecal, pode ser um problema devastador. Ela afeta homens e mulheres de todas as idades, em até 15% da população adulta. Incontinência fecal podem afetar radicalmente a vida cotidiana, como muitas pessoas que tornam-se quase reclusas, sendo incapazes de realizar tarefas simples, como fazer compras, porque estão preocupadas com as perdas fecais.

Incontinência fecal pode ser devido a um problema com os dois músculos ao redor do ânus. Estes músculos podem estar lesados ou tornarem-se fracos devido a uma injúria durante o parto ou cirurgias para o tratamento de doenças anais como hemorróidas e fístulas perianais. Os músculos anais, assim, tornam-se incapazes de segurar as fezes até que a pessoa chegue ao banheiro. O anel interno ou músculo do esfíncter anal interno normalmente mantém o ânus fechado em todos os momentos, exceto nas defecações, evitando a perda passiva de fezes. Um tratamento tem sido desenvolvido para tratar a incontinência fecal, o qual compreende a injeção de substância dentro ou próxima a este músculo, criando um enchimento, fazenso com que o ânus se oclua adequadamente. Ele vem sendo defendido como uma opção simples e efetiva.

Nesta revisão, um grande ensaio clínico demonstrou que a injeção de dextranômero estabilizado em ácido hialurónico melhora os sintomas de incontinência a curto prazo em pouco mais da metade dos que receberam o tratamento. Os outros quatro ensaiosbclínicos analisados eram de valor limitado porque eram geralmente pobres em qualidade metodológica e de pequena dimensão. Não há relatos de resultados a longo prazo para este tratamento.

Notas de tradução

Traduzido por: Pedro Luiz Toledo de Arruda Lourencao, Unidade de Medicina Baseada em Evidências da Unesp, Brazil Contato: portuguese.ebm.unit@gmail.com

平易な要約

成人の便失禁治療における肛門(直腸)周囲への充填物質の注入

排便コントロールの喪失は便失禁としても知られており、深刻な問題となりうる。成人人口の15%に上るあらゆる年齢層の男女に影響を与える。便失禁は日常生活に根本的な影響を与えるものであり、多くの人が自宅にこもりがちになり、便が漏れるのを心配するあまり、買い物などの簡単な作業もできなくなる。

便失禁は、肛門(直腸)周囲の2つの筋肉の疾患によって起こることがある。これらの筋肉は、痔や 瘻孔(皮膚と直腸の間の異常な経路)などの肛門疾患を治療するための手術や出産による傷害で、損傷したり、弱くなったりすることがある。そうなると、トイレに着くまで肛門筋が大便をとどめておくことができなくなってしまう。内輪筋や内肛門括約筋は正常な状態だと、排便時以外は常に肛門を閉じておき、便の漏出を防いでいる。開発されている便失禁の治療法は、内肛門括約筋またはその周囲へ物質を注入して分厚くし、肛門を閉じやすくする。この治療法は簡単かつ安全な選択肢として推奨されてきている。

本レビューでは、1件の大規模試験が、安定化ヒアルロン酸ナトリウムデキストラノマーを注入する治療を受けた人のうち、半数をやや上回る人で短期的に失禁症状が改善することを示した。その他に調べた4件の試験は、方法論的な質がおおむね低く小規模であったため、限定的な価値にとどまるものであった。本治療法に関する長期結果の報告はなかった。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.7.11]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Background

Description of the condition

Faecal incontinence is defined as involuntary loss of solid or liquid faeces (stools, motions). It is a distressing condition with significant social and medical implications. The prevalence of faecal incontinence may range from 1.6% to 15% depending on how it is defined, age and whether the patients are community-dwelling or living in an institution (Whitehead 2009). The symptom has a major impact on quality of life and activities of daily living, in many cases causing extreme embarrassment and discomfort. 

Faecal incontinence has many diverse causes. The maintenance of continence is a complex mechanism which consists of the interaction of an intact and functional anal sphincter complex, the consistency of the faeces, adequate cognitive ability and physical mobility, and bowel motility. Any impairment of these elements can result in incontinence.

The symptoms of incontinence have traditionally been divided into two symptom groups, urge and passive incontinence. Urge incontinence is loss of faeces following the inability to resist the urge to defaecate for long enough to reach a toilet and is primarily associated with external anal sphincter (EAS) dysfunction. Passive faecal incontinence is involuntary loss of faeces without the urge to defaecate and is predominantly associated with internal anal sphincter (IAS) dysfunction (Engel 1995 ). The multiple possible causes and contributing factors to faecal incontinence are reviewed elsewhere (Bharucha 2010; NICE 2007; Rao 2004). This review focuses specifically on treatment for passive faecal incontinence secondary to IAS weakness.

The causes of IAS dysfunction can be classified into two main groups. One is a morphologically intact but functionally weak IAS and the second is a structurally damaged IAS.

  • A structurally intact but weak IAS may be due to primary degeneration or systemic disease such as systemic sclerosis (Vaizey 1997). Radiotherapy can damage the myenteric plexus leading to diminished IAS function (Da Silva 2003).

  • Destruction of or structural damage to the IAS can be caused by anal surgery such as anal dilatation, sphincterotomy, fistula surgery and haemorrhoidectomy (Lindsey 2004). Obstetric injury such as a third or fourth degree vaginal tear may extend beyond the vagina to damage the IAS and this direct anal trauma may disrupt the structure of the IAS (Wheeler 2007).

Symptoms are likely to be exacerbated by loose faeces or incomplete rectal evacuation. The exact cause of passive soiling for an individual patient is often unclear.

Currently, the treatment for faecal incontinence associated with IAS dysfunction remains challenging. Medical management, such as modifying the consistency of the faeces by anti-diarrhoeal agents (Cheetham 2003) or pelvic floor muscle training with or without biofeedback, is effective to a certain extent (Norton 2012) but many people do not find such conservative treatment to be an ideal long term solution. The IAS is not amenable to direct surgical repair (Felt-Bersma 1996; Leroi 1997; Morgan 1997) and major surgery, such as implantation of an artificial bowel sphincter or dynamic graciloplasty, is associated with significant morbidity (Christiansen 1999; Wexner 1996). Such interventions may be disproportionate to symptoms. Sacral nerve stimulation is an emerging treatment option for faecal incontinence but has not yet been proven to be effective for IAS dysfunction. There is, therefore, a large gap between conservative and major surgical options for treating passive faecal incontinence.

This review focused specifically on one treatment that has been developed for the symptom of passive faecal incontinence secondary to IAS disruption or weakness. Although there has been an exploratory study injecting somatic muscle cells, using a similar technique to that to either fill in a defect or regenerate muscles for EAS injury (Frudinger 2010), it is not included within the scope of this review.

For further information on other interventions for faecal incontinence treatment, please refer to Cochrane reviews on:

  • surgery for faecal incontinence in adults (Brown 2010),

  • sacral nerve stimulation for faecal incontinence and constipation in adults (Mowatt 2007),

  • plugs for containing faecal incontinence (Deutekom 2012),

  • electrical stimulation for faecal incontinence in adults (Hosker 2007),

  • drug treatment for faecal incontinence in adults (Cheetham 2003),

  • biofeedback or sphincter exercises, or both, for the treatment of faecal incontinence in adults (Norton 2012), and

  • absorbent products for moderate-heavy urinary or faecal incontinence, or both, in women and men (Fader 2008).

Description of the intervention

Injection of bulking agents has emerged as a new treatment for faecal incontinence following on from reported success in treating urinary incontinence. The concept is to inject a biocompatible material in order to close the anal canal to avoid faecal incontinence. This may be performed under local, regional or general anaesthetic, and can also be used as a 'minimally invasive' treatment in an outpatient clinic setting.

Ten different materials have been used (autologous fat, Teflon, bovine glutaraldehyde cross-linked collagen, carbon-coated zirconium beads, polydimethylsiloxane elastomer, dextranomer in non-animal stabilised hyaluronic acid, hydrogel cross-linked with polyacrylamide, porcine dermal collagen, synthetic calcium hydroxylapatite ceramic microspheres, and polyacrylonitrile in cylinder form). The material can be injected either via the perianal skin or via the anal mucosa. The injection may be guided by the surgeon's finger in the anal canal or by ultrasound visualisation of placement.

How the intervention might work

The aim is to inject a biocompatible material into the submucosa of the anal canal or into the space between the anal sphincters in order to bulk out the tissue around the anal canal and approximate the anal mucosa, thereby closing the anal canal or raising the pressure inside the anal canal to prevent faecal incontinence.

Why it is important to do this review

This treatment is becoming widespread following the results of observational studies as it is potentially attractive in its simplicity and minimal invasiveness. However, it is not clear if this intervention is effective, cost effective or if any effect persists in the long term. There is no consensus regarding the indications for the treatment nor the choice of optimum material. There is little information on possible adverse events (either acute such as pain and infection or chronic such as new difficulties with evacuation). We aimed to systematically review the trials published to date and combine best evidence currently available oto base recommendations for clinical practice. 

Objectives

The objective of this review was to determine if the injection of bulking agents is better than currently available treatments or no treatment for faecal incontinence in adults in terms of effectiveness, complications and quality of life.

The following comparisons were made:

1. injection of bulking agents versus no intervention or a placebo or sham injection;

2. injection of bulking agent versus any single or combination conservative treatment (such as biofeedback, diet, anal plug, anti-diarrhoeal medication, pelvic floor exercise);

3. injection of bulking agent versus another minimally invasive or surgical intervention;

4. one type of bulking agent versus another type of bulking agent;

5. one technique of administration or injection of the agent versus another technique;

6. larger volumes of agent versus smaller volumes;

7. safety outcomes related to injectable bulking agents, information from both the included trials and non-randomised studies.

Methods

Criteria for considering studies for this review

Types of studies

All randomised or quasi-randomised controlled trials comparing the use of injectable bulking agents for faecal incontinence due to internal anal sphincter (IAS) dysfunction with any alternative treatments or placebo. Case-control and cohort studies were also reviewed to assess the safety (risks and complications) of the treatment.

Types of participants

All adults with faecal incontinence of any severity and any cause. Any trials in children were excluded as the causes of incontinence are more diverse and complex (for example congenital disorders).

Types of interventions

Injection of bulking agents (biomaterials and autologous tissues) into the anal submucosa or intersphincteric space, either via the anal mucosa or perianally, as a treatment for faecal incontinence. This included injection of autologous fat, Teflon, bovine glutaraldehyde cross-linked collagen, carbon-coated zirconium beads, polydimethylsiloxane elastomer, dextranomer in non-animal stabilised hyaluronic acid, hydrogel cross-linked with polyacrylamide, porcine dermal collagen, microballoons, polyacrylonitrile in cylinder form and synthetic calcium hydroxylapatite ceramic microspheres, and any other materials found in the literature search.

The comparison intervention could include no treatment or placebo or sham treatment, another bulking agent, conservative treatment (for example biofeedback, anal plug, diet, anti-diarrhoeal medication, pelvic floor exercise), minimally invasive treatment (for example sacral nerve stimulation, radio-frequency ablation) and surgical intervention.

Different injection techniques were also compared to determine whether one technique was superior to another.

Types of outcome measures

There are a range of outcome measures which can be used to assess the effectiveness and safety of the treatment as listed below.

Primary outcomes
  • Change in incontinence scores (e.g. Wexner or Cleveland Clinic Florida Fecal Incontinence Score (CCFIS) or St Mark's incontinence score)

Secondary outcomes
Patient reported outcomes

Subjective assessment of change by the patient (improved, no change, or deterioration in incontinence); symptoms; ability to conduct activities of daily living; satisfaction or dissatisfaction with treatment; need for additional therapy (need to wear absorbent products for incontinence, use of drugs, dietary changes, repeat procedure)

Clinician observation

Physiological measures (maximum resting anal pressure, maximum squeeze anal pressure, mucosal electrosensitivity). Evidence of migration of material by imaging or examination. Further surgical intervention for faecal incontinence (including formation of colostomy)

Quality of life

Generic and condition-specific change in quality of life scores such as Fecal Incontinence Quality of Life Scale (FIQL); measures of psychological well-being

Adverse effects

Post-operative complications (e.g. bleeding, infection, injection site or anal pain or discomfort, new evacuation difficulty)

Health economics

Length of hospital stay, costs

Search methods for identification of studies

This review has drawn on the search strategy developed by the Cochrane Incontinence Group. We did not impose any language or other limits on the searches.

Electronic searches

Relevant trials were identified from the Incontinence Group Specialised Register of controlled trials, which is described under the Incontinence Group module in The Cochrane Library. The register contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL and handsearching of journals and conference proceedings. The date of the most recent search of the Specialised Register for this review was 25 May 2012.

The trials in the Incontinence Group Specialised Register are also contained in CENTRAL.

The terms used to search the Incontinence Group Specialised Register are given below:

(({DESIGN.CCT*} OR {DESIGN.RCT*}) AND {TOPIC.FAECAL*} AND {INTVENT.SURG.INJECT*})

(All searches were of the keyword field of Reference Manager 12, ISI ResearchSoft).

Additional trials were sought by one of the review authors from the UK National Research Register, Controlled Clinical Trials and the ZETOC database of conference abstracts (searching specifically the American, European, Australasian and UK Societies of Colorectal Surgeons meeting abstracts for the past 10 years). The search was conducted on 3 May 2012 using appropriate free text and MeSH terms by adapting terms drawn from the existing search strategies for the Incontinence Review Group to meet the objectives of this review. Keywords used included: fecal incontinence, durasphere, silicone, collagen, biocompatible materials, polydimethylsiloxane, polyacrylamide, dextranCopolymer, hyaluronicAcid, polyacrylonitrile, AdverseEvents.

Searching other resources

The review authors also searched all the reference lists of relevant articles.

Data collection and analysis

Two review authors (YM, CN) examined all the citations and abstracts derived from the above search strategy. Reports of relevant trials were retrieved in full. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Data were analysed using Review Manager (RevMan Version 5.1.7).

Selection of studies

The titles and abstracts of all studies identified from the above search strategy were independently assessed for potential eligibility by two review authors (YM, CN) and the full papers were obtained for all studies considered eligible. Any disagreements were resolved by consultation with the third review author (SL). Randomised controlled trials (RCTs) and quasi-RCTs only were included for the efficacy review.

All other study designs (for example case series of any design, any length of follow up and sample size) were reviewed for reports of adverse events and complications. This review for adverse events forms a separate section of the review and specifically alerts the reader to the different search method employed.

Data extraction and management

Data extraction from the included trials were undertaken independently by the two review authors (YM, CN). Data from RCTs and quasi-RCTs were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0) (Higgins 2011). Data were analysed using the RevMan analyses statistical programme in Review Manager. Data on adverse events and complications were extracted and entered onto an Excel spreadsheet for review and analysis by all three review authors.

Assessment of risk of bias in included studies

The methodological quality of all included RCTs and quasi-RCTs was evaluated by two review authors (YM and CN) using the criteria recommended by the Cochrane Incontinence Review Group to assess risk of bias. In particular, trials were assessed for randomisation procedure, blinding, adequacy of allocation concealment and attrition bias.

Measures of treatment effect

If appropriate, the results of included studies were combined for each outcome in a formal meta-analysis to produce an overall estimate of treatment effect. For dichotomous data the risk ratio (RR) and 95% confidence interval (CI) were derived using a fixed-effect model, and for continuous data weighted mean differences (WMD), weighted by the inverse of the variance, were calculated.

Unit of analysis issues

There were no non-standard designs.

Dealing with missing data

Trials were assessed as to whether the results were reported on attrition bias, and if not the number and reasons for withdrawals and drop-outs were sought.

Assessment of heterogeneity

Analysis of variation across the trials was considered if the number of available trials was sufficient to conduct such an assessment.

Assessment of reporting biases

The potential bias was reported as published.

Data synthesis

It was intended to perform a meta-analysis using a fixed-effect model if data were available.

Subgroup analysis and investigation of heterogeneity

If data allowed, subgroup analyses would have been undertaken according to: cause of incontinence; sphincter integrity; gender; and injection technique.

Sensitivity analysis

Sensitivity analyses would have been performed if data allowed, such as according to the quality (risk of bias) of trials.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of ongoing studies.

Five randomised trials were included in this review. In total, 382 patients were randomised (Graf 2011; Maeda 2008; Siproudhis 2007; Tjandra 2004; Tjandra 2009).

Results of the search

Twenty records were identified by the search of which four were not relevant and were excluded. Sixteen full text reports were assessed and one was excluded as it was not a randomised trial. Eight reports of five studies were eligible for inclusion in the review. Additionally, there were seven studies that still appeared to be ongoing: one (Smart 2008) was a communication about an ongoing trial and the results were not yet available in the public domain at the time of the search; one study (NCT00762047 2009) appeared to have been terminated in 2009 (reasons unknown, trialists contacted for details); and three were ongoing studies for EAS injuries using cell therapy. The flow of study selection is summarised in Figure 1.

Figure 1.

PRISMA study flow diagram,

Included studies

The five randomised trials (Graf 2011; Maeda 2008; Siproudhis 2007; Tjandra 2004; Tjandra 2009) included a total of 382 patients. Further details are in the Characteristics of included studies table.

The participants in all five RCTs had internal anal sphincter (IAS) dysfunction or passive faecal incontinence and were reported to have failed previous conservative management with anti-diarrhoeal drugs and pelvic floor muscle training or biofeedback (although this was not standardised and generally not reported in any detail).

The interventions tested were:

  • hydrogel cross-linked with polyacrylamide (Bulkamid) (Maeda 2008);

  • porcine dermal collagen (Permacol) (Maeda 2008);

  • polydimethylsiloxane elastomer implants (Siproudhis 2007);

  • silicone biomaterial (PTQ) injected between the two anal sphincters (Tjandra 2009);

  • carbon-coated beads injected into the anal submucosa (Durasphere) (Tjandra 2009);

  • two different injection techniques (endoanal ultrasound guidance or digital guidance) using a silicone biomaterial (PTQ) (Tjandra 2004);

  • dextranomer in stabilised hyaluronic acid (NASHA Dx) (Graf 2011).

The control intervention in two trials were:

  • saline (Siproudhis 2007);

  • sham injection (mimicking active treatment but without injection of any substance) (Graf 2011).

The injection sites were:

Excluded studies

See the Characteristics of excluded studies table. One study was not an RCT (Dehli 2007).

Risk of bias in included studies

Risk of bias was assessed in summary (Figure 2) and in each trial (Figure 3).

Figure 2.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figure 3.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Allocation

Two trials gave sufficient details about the randomisation process to suggest freedom from bias (sequence generation in a central registry) (Graf 2011; Tjandra 2009). The quality of allocation concealment was judged to be unclear in three trials.

Blinding

In two trials (Graf 2011; Siproudhis 2007), the patients and the outcome assessors were blinded to treatment allocation. The other three trials did not specify whether the assessor was different from the person involved in the treatment.

It was not possible to blind the surgeons in any of the trials as the interventions were different.

Incomplete outcome data

Withdrawals and intention to treat

Three trials reported no drop-outs, one presented a flow of patients with figures (Graf 2011), and one had a high drop-out rate (Tjandra 2004). From the number of people included at the start and the results of the trial, four trials analysed data on an intention-to-treat basis (Graf 2011; Maeda 2008; Siproudhis 2007; Tjandra 2009) whilst one trial conducted an available case analysis (Tjandra 2004).

Follow up

Follow up varied from three to 12 months. No long term results were presented.

Selective reporting

Review authors considered there was no evidence of selective reporting.

Other potential sources of bias

There are six ongoing trials (Dehli 2007; Dehli 2009; Draganic 2008; EUCTR2010-021463-32-AT 2011; Michot 2012; Norderval 2012). Five studies are ongoing with three of them aiming to regenerate muscles by cell therapy for external anal sphincter injuries, hence they are not under the scope of the current review. One study has been completed and is under preparation for publication (personal communication).

Effects of interventions

1. Injection of bulking agent versus placebo or sham injection

Two trials addressed this comparison.

Siproudhis et al (Siproudhis 2007) compared a silicone biomaterial (polydimethylsiloxane elastomer, PTQ) with a (control) normal saline injection into the intersphincteric space. The trial was too small to detect differences in any outcomes, such as failure rate (17/22, 77% versus 16/22, 72% in the control group, RR 1.06, 95% CI 0.75 to 1.50; Analysis 1.1); use of pads (Analysis 1.3) or Wexner score (Analysis 1.5). In addition, the subjective perception of treatment success was low in both groups (23% versus 27%, P = 0.73).

The study by Graf et al (Graf 2011) compared injection of dextranomer stabilised in hyaluronic acid (NASHA Dx) against sham injection (injection without actual substance). The primary endpoint was a response to treatment which was defined as a 50% or greater reduction in the number of incontinence episodes. There was a statistically significant difference between the treatment and control groups at six months (65/136, 48% versus 48/70, 69% participants not improved, defined as less than 50% reduction in incontinence episodes, RR 0.70, 95% CI 0.55 to 0.88; Analysis 1.2). Participants in the active group had statistically significantly more incontinence free days at six months (3.1 days compared with 1.7 in the sham treatment group, MD 1.40 days, 95% CI 0.33 to 2.47; Analysis 1.4). However, this difference was not shown at three months. Secondary endpoints such as number of faecal incontinence episodes, CCFIS at three and six months and FIQOL at 12 months did not show any difference except for one domain of FIQOL between the active and sham treatment groups. While there were fewer adverse events in the control group (128/136, 94% in the active group versus 29/70, 41% in the control group, RR 2.27, 95% CI 1.71 to 3.01; Analysis 1.6.2), only two in the active group were regarded as serious (rectal and prostate abscesses).

2. Injection of bulking agent versus conservative treatment

No trials were found.

3. Injection of bulking agent versus another minimally invasive or surgical intervention

No trials were found.

4. One type of bulking agent versus another type

Two trials addressed this comparison (Maeda 2008; Tjandra 2009).

In the trial by Tjandra and colleagues (Tjandra 2009), injection of the silicone biomaterial polydimethylsiloxane elastomer (PTQ™) and carbon-coated beads (Durasphere®) were compared. While participants in both groups reported an improvement in Wexner's score and quality of life over the study period up to 12 months, the silicone material was better than the carbon-coated beads in terms of: faecal incontinence at six and 12 months (for example at 12 months, RR 0.15, 95% CI 0.04 to 0.60; Analysis 2.1); Wexner's incontinence score at six and 12 months (for example at 12 months, MD -3.20, 95% CI -4.91 to -1.49; Analysis 2.2); and quality of life (lifestyle) index at six months (MD -0.56, 95% CI -1.01 to -.011; Analysis 2.3). There were more adverse effects (4/20 in the silicone group versus 8/20 in the carbon-coated bead group; Analysis 2.4); one serious event occurred in the carbon-coated bead group only (Analysis 2.5). It was assumed that there were no drop-outs, though this was not explicitly stated.

Another trial with only 10 participants (Maeda 2008) compared injection of hydrogel cross-linked with polyacrylamide (Bulkamid™) and porcine dermal collagen (Permacol™). In the hydrogel group incontinence scores improved from a median of 15 to 12 at six weeks and this was maintained at six months. In the porcine dermal collagen group, the baseline median score improved from 16 to 14 at six weeks but deteriorated to 15 at six months. The trial was too small to detect differences between the groups in terms of faecal incontinence becoming worse (Analysis 2.1), the overall St Mark's incontinence score, or the faecal incontinence quality of life score, but data were not provided in a form suitable for analysis (medians and no SDs).

5. One technique of administration of agent compared to another technique

One trial (Tjandra 2004) compared a silicone biomaterial, polydimethylsiloxane elastomer (PTQ™), injection under endoanal ultrasound guidance versus digital (finger) guidance. Using a criterion of greater than 50% decrease (improvement) in the Wexner scale, the ultrasound technique was better than the digital technique (RR 0.53, 95% CI 0.31 to 0.92; Analysis 3.1, Analysis 3.2) and improved the Quality of Life (lifestyle) index at six months (MD -0.60, 95% CI -0.92 to -0.28; Analysis 3.3). The only reported adverse effect, discomfort at the injection site, was rare (2/42 and 4/40 participants; Analysis 3.4). However, many of the data were reported in a form not suitable for analysis (medians and no SDs), the follow up was short (12 months), and there was a high drop-out rate (by 12 months, 32/42 and 35/40 respectively).

6. Larger volumes of agent versus smaller volumes

No trials were found.

7. Safety data in included RCTs and other non-randomised studies

Adverse effects were reported in four of the five included trials (Graf 2011; Siproudhis 2007; Tjandra 2004; Tjandra 2009). In the randomised trials included in this review, one trial (Siproudhis 2007) reported 18 adverse effects in nine people (Analysis 1.6). Six out of 22 people injected with silicone biomaterial (PTQ™) complained of pain at the implant site, whilst two out of 22 people in the saline group complained of pain. Anal inflammation was noted in two people in the silicone biomaterial injection group compared to none in the normal saline group. The severity of these adverse effects was categorised as 'not serious' but the duration of the events was not reported. In the trial reported by Graf et al (Graf 2011), patients treated with dextranomer stabilised in hyaluronic acid (NASHA Dx) reported 128 adverse events (number of patients not stated) whilst 29 events (number of patients not stated) were recorded in the sham treatment group (Analysis 1.6). The most common event was proctalgia (19/136 versus 2/70) followed by injection site bleeding (7/136 versus 12/70) and rectal haemorrhage (10/136 versus 1/70). Two serious events were reported in the active treatment group, one was a prostatic abscess resolved by antibiotic treatment and the other was a rectal abscess which required surgical drainage. The trial comparing silicone biomaterial (PTQ™) and carbon-coated beads (Durasphere®) (Tjandra 2009) reported no septic or significant complications in patients injected with PTQ™, although there were four occurrences of bruising. In contrast, patients who had a Durasphere® injection complained of rectal pain (1/20), erosion of rectal mucosa (2/20) and type III hypersensitivity reaction in small joints and skin (1/20) (Analysis 2.4). One of these type III hypersensitivities was judged to be serious and resulted in hospital admission for seven days (Analysis 2.5). The trial comparing injection techniques (Tjandra 2004) reported minor discomfort in two of 42 patients who had injections with ultrasound guidance and four of 40 patients with digital guidance (Analysis 3.4); in one patient this persisted for six weeks. There were no reports of other serious adverse effects (Analysis 3.5).

The occurrence of complications was also investigated in all non-randomised studies found to date and is summarised in Table 1. In general, the complications were poorly reported.The severity and duration of complications were rarely reported and in some studies there was no mention of whether or not there had been any complications. The complications were mostly minor (discomfort, pain, bleeding, leakage of injected material). One rectovaginal fistula was reported although it was not clear if this was related to the injection. The reason for discontinuation of one study (NCT00762047 2009) is unclear and there is no information on adverse events in this study.

Table 1. Summary of complications
  1. Bioplastique™/PTQ™: Silicone biomaterial

    Bulkamid™: Hydrogel cross-linked with polyacrylamide

    Coaptite®: Calcium hydroxylapatite

    Contigen®: Synthetic bovine collagen

    Durasphere®/ACYST-TM: Carbon-coated microbeads

    NASHA™Dx: Stabilized nonanimal hyaluronic acid with dextranomer

    Permacol™: Porcine dermal collagen

    Teflon®: Polytetrafluoroethylene

    Urosurge®: Expandable silicone microballoon

AgentAuthors and YearNo of patientsInjection routeTotal volumeComplicationsNumber of adverse effects/Number of participants
Autologous fatShafik 199514Submucosal15-20mlReports that there were no complications0/14
Bernardi 19981Perianal130mlReports that there were no complications0/1
Bioplastique™/PTQ™Malouf 200110Perianal5-11.5ml4 anal canal ulcer, 1 injection site pain, 1 leakage of injected material6/10
Tjandra 200482Perianal10.0ml6 minor discomfort at injection site (4: digital guidance group, 2: ultrasound guidance group)6/82
Chan 20067PerianalNot mentionedReports that there were no complications0/7
de la Portilla 200720Perianal7.5mlNot reportedNot reported
Maeda 20076Perianal7.5ml1 recto-vaginal fistula1/6
van der Hagen 200724Perianal7.5mlNot reportedNot reported
Gett 200737Not mentionedNot mentioned4 perianal abscess required surgical drainage4/37
Siproudhis 200722Perianal7.5ml6 pain at the implant site, 2 anal inflammation8/22
Soerensen 200933Perianal7.5mlReports that there were no complications0/33
Tjandra 200920Perianal10.0ml4 bruising4/20
Bartlett 200974Perianal10.0ml9 minor complications9/74
van Wunnik 201250PerianalNot mentioned2 local giant cell foreign body reaction2/50
Bulkamid™Maeda 20085Perianalmedian 9ml (8-9)Reports that there were no complications0/5
Coaptite®Ganio 200810Perianal4ml1 leakage of Coaptite®1/10
Contigen®Kumar 199817Submucosal2mlReports that there were no complications0/17
Stojkovic 200673Submucosal5mlNot reportedNot reported
Durasphere®/ACYST-TMWeiss 20027Submucosalaverage 6.8mlNot reportedNot reported
      
Davis 200318Submucosalmean 1.28ml at 1-4 sites2 anal discomfort, 1 exacerbation of pruritis ani, 2 passage of injected Durasphere via anus5/18
Altomare 200833Submucosalmedian 8.8ml (2-19ml)2 anal pain, 1 Durasphere® leakage, 2 material migration5/33
Aigner 200911Perianalmean 9ml (8-12ml)Local pain (most frequent, no numbers reported), 3 passage of Durasphere®At least 3/11
Tjandra 200920Submucosal10.0ml4 bruising, 2 erosion of rectal mucosa, 1 rectal pain, 1 type III hypersensitivity8/20
Gatekeeper™ (polyacrylonitrile)Ratto 201114Perianal1 cylinder (length 21mm, diameter 1-2mm)x4Reports that there were none.0/14
NASHA™DxDehli 20074Submucosal5.6ml1 bleeding settled with compression, 1 anal pain, 1 tenesmus. All complications settled within 2-7 days after procedure.3/4
Danielson 200934Submucosal4mlPain (26% during 1st injection procedure, 55% for second treatment), 3 suspected inflammation of anal canal, 2 sensation of obstructed defaecationAt least 5/34
Graf 2011136Submucosal4-8ml128 adverse events in total. Two serious events, one prostatic abscess and one rectal abscess.128/136
Dodi 2010115Submucosalup to 4ml154 adverse events, including 20 serious events such as abscess and haemorrhage154 adverse events by 70 patients
Permacol™Smart 20057SubmucosalNot mentionedReports that there were no complications0/7
Maeda 20085Perianalmedian 15ml (15-17.5)Reports that there were no complications0/5
SalineSiproudhis 200722Perianal7.5ml2 pain at the implant site2/22
Synthetic collagenUllah 201111SubmucosalNot specifiedOne death unrelated to the treatment1/11
Teflon®Shafik 199311Submucosal10mlNot reportedNot reported
Urosurge®Feretis 20016Submucosalup to 5 balloons1 bleeding, 1 lost balloon after 2 months (potential spontaneous burst)2/6

Most studies do not appear to have systematically and prospectively collected data on adverse events, but instead reported those which came to the investigators' attention.

Discussion

Since the publication of the last version of this review, a large adequately-sized trial has emerged which demonstrated the short term efficacy of dextranomer stabilised in hyaluronic acid (NASHA Dx) injection for faecal incontinence. The study showed 52% of patients in the active treatment group had a 50% or greater reduction in the number of incontinence episodes compared to 31% of those who had a sham injection. Although this definition of successful treatment is rather arbitrary, there were significantly more patients who achieved this primary outcome compared to sham injection.

It is interesting to note that nearly 30% of the patients in the sham injection group also achieved this primary outcome, which is compatible with another trial that used saline injection as control. The placebo effect cannot be negated as the sham group experienced improvement up to six months. The mechanism of action is obscure.

There remains a shortage of well-designed randomised trials to evaluate the efficacy of perianal injection of bulking agents, and the studies reviewed failed to answer other important questions surrounding this treatment. There are wide variations in the agents and techniques used (submucosal versus intersphincteric, use of transanal ultrasound). Safety and potential complications have not been thoroughly assessed and the quality of reports has generally been poor. This needs further, more rigorous evaluation with longer term follow up for potential adverse events. The selection criteria for patients and the primary outcome measure, thus the definition of successful treatment, have been variable. These important questions surrounding this treatment need to be addressed in a well-designed RCT with adequate power to assess the outcomes.

There appears to be a gap between patients' subjective evaluation of their symptoms and the incontinence scores, particularly in observational studies. Regardless of the outcome of the scores the trials in this review all showed improvement in a faecal incontinence quality of life scale, and thus this discrepancy needs to be addressed in future research.

Summary of main results

One large randomised trial has shown that dextranomer stabilised in hyaluronic acid (NASHA Dx) is efficacious to treat faecal incontinence (Graf 2011). The injection was effective up to 12 months.

Several of the studies showed that there were short term improvements in faecal incontinence after injections of a variety of materials or with injection techniques. Some materials were better than others, at least in the short term, as silicone material was better than the carbon-coated beads (Tjandra 2009). Similarly, ultrasound-guided injections seemed to have short term benefits over digital guidance (Tjandra 2004).

Two trials comparing active treatment against sham injection showed an improvement of symptoms in up to 27% of the control treatment group, thus the possibility of placebo effect should be noted.

Complications are common but mostly appear to be relatively minor and of short duration, resolving spontaneously in most cases. There has been no long term follow up of RCT results published to date.

Overall completeness and applicability of evidence

The number of studies available to address the objectives of this review was limited.

There is a lack of information regarding the volume, the precise location where the agent should be placed, and the choice of guidance of the needle track.

Quality of the evidence

Only two of the studies provided enough data to reliably assess the chance of bias, and most of the studies were small with short duration of follow up. Some studies did not supply data in a form suitable for analysis.

Potential biases in the review process

The number of references identified was small. The limitations of this review are the variable outcome measures used in eligible trials and that meta-analysis was not possible.

Agreements and disagreements with other studies or reviews

Similar reviews which included case-series (Hussain 2011; Luo 2010) reached the same conclusion that evidence on the efficacy of this treatment is weak and most studies conducted for this treatment have been of poor quality.

Authors' conclusions

Implications for practice

A single large trial demonstrated that perianal injection of a bulking agent is effective in treating faecal incontinence for up to one year. In other reported studies to date, patients experienced an improvement in symptoms in the short term. No studies evaluated the long term benefit on symptoms of passive faecal incontinence. 

A review of all the observational non-randomised studies published to date indicates that the injection of biomaterial appears relatively safe and although minor adverse events are relatively common, they are probably unlikely to do any serious harm. However, in view of the poor quality of reporting complications and small sample sizes these conclusions can only be tentative.

Implications for research

There is a need for more well-designed randomised controlled trials with adequate sample sizes, validated outcome measures (particularly those reported by participants) and long term follow up. The longest follow up in the reviewed trials was 12 months. Currently it is unknown whether the injection of bulking agents causes any medium term or long term benefit or adverse events. Therefore systematic long term monitoring of participants is necessary together with evaluation of the efficacy and location of the material by endoanal ultrasonography. Further work on the mechanism for any benefit is also needed.

Adoption of agreed definitions or classification of the type of faecal incontinence is required to improve comparability of the studies and facilitate a robust systematic review of trials. In particular, the clinical relevance of the most commonly used primary endpoint, an incontinence score, remains to be validated in terms of patient evaluation of the effect of treatment.

Acknowledgements

The authors would like to thank Sheila Wallace for her help and advice with the electronic search strategy.

Data and analyses

Download statistical data

Comparison 1. Injectable versus placebo injection
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure (number of participants with Wexner's >8)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
1.1 Silicone material (PTQ) versus saline1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
2 No improvement (less than 50% reduction in incontinence episodes1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
2.1 Dextranomer stabilised in hyaluronic acid (NASHA Dx) versus sham injection1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Number of participants wearing pads every day1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
3.1 Silicone material (PTQ) versus saline1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Number of incontinence free days at 6 months1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
4.1 Dextranomer stabilised in hyaluronic acid (NASHA Dx) versus sham injection1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Wexner score (mean)1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
5.1 Silicone material (PTQ) versus saline1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
6 Number of adverse effects2 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
6.1 Silicone biomaterial (PTQ) versus saline injection1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
6.2 Dextranomer stabilised in hyaluronic acid (NASHA Dx) versus sham injection1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
7 Serious adverse effects1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
7.1 Dextranomer stabilised in hyaluronic acid (NASHA Dx) versus sham injection1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
8 Need for re-treatment at 6 months1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
8.1 Dextranomer stabilised in hyaluronic acid (NASHA Dx) versus sham injection1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 1.1.

Comparison 1 Injectable versus placebo injection, Outcome 1 Failure (number of participants with Wexner's >8).

Analysis 1.2.

Comparison 1 Injectable versus placebo injection, Outcome 2 No improvement (less than 50% reduction in incontinence episodes.

Analysis 1.3.

Comparison 1 Injectable versus placebo injection, Outcome 3 Number of participants wearing pads every day.

Analysis 1.4.

Comparison 1 Injectable versus placebo injection, Outcome 4 Number of incontinence free days at 6 months.

Analysis 1.5.

Comparison 1 Injectable versus placebo injection, Outcome 5 Wexner score (mean).

Analysis 1.6.

Comparison 1 Injectable versus placebo injection, Outcome 6 Number of adverse effects.

Analysis 1.7.

Comparison 1 Injectable versus placebo injection, Outcome 7 Serious adverse effects.

Analysis 1.8.

Comparison 1 Injectable versus placebo injection, Outcome 8 Need for re-treatment at 6 months.

Comparison 2. One injectable material versus another
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure (number with worse faecal incontinence)2 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
1.1 hydrogel crosslinked with polyacrylamide versus porcine dermal collagen1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere) at 6 months1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
1.3 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere) at 12 months1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Wexner's incontinence score1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere) at 6 months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere) at12 months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Quality of life index (lifestyle) at 6 months1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere) at 6 months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
3.2 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere) at 12 months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Adverse effects1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
4.1 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere)1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Serious adverse effects1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5.1 silicone biomaterial (PTQ) versus carbon-coated spheres (Durasphere)1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 2.1.

Comparison 2 One injectable material versus another, Outcome 1 Failure (number with worse faecal incontinence).

Analysis 2.2.

Comparison 2 One injectable material versus another, Outcome 2 Wexner's incontinence score.

Analysis 2.3.

Comparison 2 One injectable material versus another, Outcome 3 Quality of life index (lifestyle) at 6 months.

Analysis 2.4.

Comparison 2 One injectable material versus another, Outcome 4 Adverse effects.

Analysis 2.5.

Comparison 2 One injectable material versus another, Outcome 5 Serious adverse effects.

Comparison 3. One method of injection versus another
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure (number of participants with Wexner's score <50% improved)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
1.1 Endoanal ultrasound guidance versus digital guidance1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Failure (number of participants global Quality of Life score <50% improved)1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
2.1 Endoanal ultrasound guidance versus digital guidance1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Quality of life index (lifestyle) at 6 months1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
3.1 Endoanal ultrasound guidance versus digital guidance1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Discomfort at injection site1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
4.1 Endoanal ultrasound guidance versus digital guidance1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Adverse effects1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5.1 Endoanal ultrasound guidance versus digital guidance1 Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 3.1.

Comparison 3 One method of injection versus another, Outcome 1 Failure (number of participants with Wexner's score <50% improved).

Analysis 3.2.

Comparison 3 One method of injection versus another, Outcome 2 Failure (number of participants global Quality of Life score <50% improved).

Analysis 3.3.

Comparison 3 One method of injection versus another, Outcome 3 Quality of life index (lifestyle) at 6 months.

Analysis 3.4.

Comparison 3 One method of injection versus another, Outcome 4 Discomfort at injection site.

Analysis 3.5.

Comparison 3 One method of injection versus another, Outcome 5 Adverse effects.

What's new

Last assessed as up-to-date: 25 May 2012.

DateEventDescription
21 January 2013New citation required and conclusions have changedNew studies have been added and the conclusions changed.
21 January 2013New search has been performedNew studies have been added and the conclusions changed.

Contributions of authors

Yasuko Maeda and Christine Norton examined all the materials derived from the electronic search strategy. Yasuko Maeda and Christine Norton wrote the first draft of the review. Søren Laurberg helped with the design of the protocol, the interpretation of the data, and contributed to the final version of the review.

Declarations of interest

Yasuko Maeda is an author of a study included in this review.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • NIHR, UK.

    The Cochrane Incontinence Review Group is supported by NIHR UK

Differences between protocol and review

None

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Graf 2011

Methods

Randomised, double-blind, sham-controlled trial

Muticentre, USA and Europe

Participants

206 patients with Cleveland Clinic Florida Faecal Incontinence (CCFIS) of 10 or more and at least four recorded incontinence episodes in 2 weeks, had symptoms for at least 12 months

NASHA Dx group: median 61.8 years (interquartile range 55.5-68.3), sham group: median 60.1 years (interquartile range 51.3-66.7)

Interventions

Intervention: Injection of 4-8mls dextranomer in stabilised hyaluronic acid (NASHA Dx)

Control: Sham injection (the procedure mimicked active treatment without injection of any substance)

Outcomes

Primary endpoint: A reduction in number of incontinence episodes by 50% or more compared with baseline. Number of patients achieving this endpoint: NASHA Dx group 71 patients (52%), sham group 22 patients (31%).

Secondary endpoints: Change from baseline in number of incontinence free days. Number of faecal incontinence episodes, and CCFIS at 3 months and 6 months. Adverse events.

Mean increase in incontinence free days at 6 months: NASHA Dx 3.1 days, sham group 1.7 days (p=0.0156). Decrease in number of faecal incontinence episodes at 3 months: NASHA Dx 4.8, sham 3.0 p=0.14, and at 6 months: NASHA Dx 6.0, sham 3.0, p=0.09. Change in CCFIS at 3 months: NASHA Dx 2.6, sham 2.0, and at 6 months: NASHA Dx 2.5, sham 1.7, both differences stated as not statistically significant but no p values provided.

Adverse events: NASGHA Dx 128 events, sham group 29 events

Number of people requiring retreatment: Intervention 112/136, control 61/70

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomisation stratified by sex and region (USA versus Europe) in block of six, and managed with an automated, real-time, central web-based system
Allocation concealment (selection bias)Unclear riskNo data
Blinding (performance bias and detection bias)
Participants
Low riskPatients were masked to treatment during the first 6 months
Blinding (performance bias and detection bias)
Surgeons
High riskNot possible
Blinding (performance bias and detection bias)
Outcome assessors
Low riskMasked to treatment during the first 6 months
Incomplete outcome data (attrition bias)
All outcomes
High risk16 participants dropped out. Sham group were followed up only up to 6 months

Maeda 2008

Methods

Randomised single-blinded treatment

Single centre, UK

Participants

10 patients, 9 female, median age 68 years, range 45 to 79

Inclusion: Passive faecal incontinence to solid or liquid stool secondary to internal anal sphincter dysfunction; failure of antidiarrhoeal drugs and biofeedback

Interventions

A (n=5): Bulkamid™ (hydrogel cross-linked with polyacrylamide) mean volume 9ml

B (n=5): Permacol™ (porcine dermal collagen) mean volume 15ml

General anaesthetic, prophylactic antibiotics (cephalosporin and metronidazole), injection into the intersphincteric space under digital guidance

Outcomes

St Mark's incontinence score, faecal incontinence quality of life scale, Short Form-36 health survey, 1-week bowel diary card

Outcomes at 19 months: A 4/5 improved, 1/5 worse; B 1/4 improved, 2/4 same, 1/4 worse

St Mark's Continence score at 6 months (median [range]): A 12 [6 to 18], B 15 [8 to 22]

Faecal incontinence QoL score increased in both groups during 6 months follow up, no difference between groups

NotesPilot study
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomisation schedule predetermined before recruitment to ensure equal distribution
Allocation concealment (selection bias)Unclear riskProspectively randomised
Blinding (performance bias and detection bias)
Participants
Unclear riskNo data
Blinding (performance bias and detection bias)
Surgeons
High riskNot possible
Blinding (performance bias and detection bias)
Outcome assessors
Unclear riskNo data
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo drop-outs

Siproudhis 2007

Methods

Randomised double-blind trial (participants and outcome observers blinded)

Single centre, France

Participants

44 female patients (mean age 64.3 years, standard deviation 9) with passive incontinence and Wexner's incontinence score of 9 or more (classed as severe faecal incontinence)

Groups comparable at baseline

Interventions

A (n=22): Injection of polydimethylsiloxane elastomer implants (7.5ml)

B (n=22): Saline (control)

Local anaesthetic, prophylactic lactulose and antibiotic (metronidazole), injection perianally into the inter-sphincteric space

Outcomes

Success defined as a Wexner's score 8 or less at 3 months after injection

Failure (Wexner's score >8): A 17/22, B 16/22

Need to wear pads every day: A 17/22, B 15/22

Wexner's score at 3 months (mean (SD) N): A 11.7 (4.7) 22, B 11.4 (4.5) 22 P=0.79

Adverse effects related to intervention (n/N of participants): A 7/22, B 2/22

NotesOutcome table seems to provide data for 24 participants in each group (but only 22 randomised)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot mentioned
Allocation concealment (selection bias)Unclear riskRandomisation method not mentioned
Blinding (performance bias and detection bias)
Participants
Low riskYes
Blinding (performance bias and detection bias)
Surgeons
High riskNot possible
Blinding (performance bias and detection bias)
Outcome assessors
Low riskDoctor and nurse blinded to allocation and intervention
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo drop-outs

Tjandra 2004

Methods

Randomised single-blind trial of different injection technique

Single centre, Australia

Participants

82 patients, 64 females, median 66 years, range 34 to 89

Inclusion: severe faecal incontinence, low anal resting pressure, internal anal sphincter dysfunction

Exclusion: pregnancy, active perianal sepsis, unresected anorectal cancer, immunosuppression

Groups comparable at baseline on age, gender, past anorectal surgery, duration of follow up (median 6 months, range 1 to 12), baseline continence score

Follow up at 1, 3, 6, 9 and 12 months

Drop-outs: at 3 months A 4, B 8; at 6 months A 12, B 19; at 12 months A 32, B 35

Interventions

A (42): Injection under endoanal ultrasound guidance

B (40): Injection under digital guidance

Local anaesthetic, prophylactic antibiotics (cephalosporin and metronidazole)

Both groups had 10ml silicone biomaterial injected into the intersphincteric space

Outcomes

Wexner's continence score, global quality of life on visual analogue scale, faecal incontinence quality of life scale

Number achieving >50% improvement in Wexner's continence score at 3 months: A 26/38, B 13/32 (failure: A 12/38, B 19/32)

Wexner's score at 6 months (median (range) N: A: 5 (2 to 13) B 8 (2 to 12)

Wexner's score at 12 months: A 3 (1 to 12), B 11 (2 to 12)

Number achieving >50% improvement in global QoL score at 3 months: A 35/38, B 29/32 (not improved: A 3/38, B 3/32)

Faecal Incontinence Quality of Life index lifestyle at 6 months (mean (SD) N): A 3.7 (0.44) 42, B 3.1 (0.83) 31

Adverse effects: A 0/42, B 0/40

Discomfort at injection site: A 2/42, B 4/40

Notes

Data provided as medians and ranges, precluding meta-analysis

Wexner's score: higher = worse outcome

Visual analogue score, FI QoL score: higher = better outcome

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo data
Allocation concealment (selection bias)Unclear risk"Randomized"
Blinding (performance bias and detection bias)
Participants
Unclear riskNo data
Blinding (performance bias and detection bias)
Surgeons
High riskNot possible
Blinding (performance bias and detection bias)
Outcome assessors
Unclear riskNo data
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskAdjustment for multiple comparisons but high drop-out rate

Tjandra 2009

Methods

Randomised single-blinded study

Single centre, Australia

Participants

40 patients (36 male, 4 female)

Inclusion: faecal seepage or soiling for more than twice a week caused by internal sphincter dysfunction, low or borderline resting anal canal pressure, failed 6 months' treatment with pelvic floor exercise and stool bulking agents

Exclusion: perianal sepsis, anorectal cancer, immunosuppression, rectal prolapse, inflammatory bowel disease, congenital anorectal malformation, neurological disorders (e.g. Parkinson's disease, multiple sclerosis, spinal cord injury), stoma in situ, pregnancy, external anal sphincter defect >120oof circumference, bleeding diathesis, mental or physical disability precluding adherence to protocol

Use of antidiarrhoeal medications not allowed during study period.

Baseline Wexner's score 11.5

Groups comparable at baseline on Wexner's score, age, past obstetric history, previous anorectal surgery, FIQL and SF-12

Interventions

A (20): Intersphincteric injection with silicone biomaterial (PTQ) 10ml

B (20): Submucosal injection with carbon-coated beads (Durasphere) 10ml

Enema, local anaesthetic, prophylactic antibiotics (cephalosporin and metronidazole), day case procedure

Outcomes

Wexner's incontinence score, faecal incontinence quality of life scale, Short Form 12 health survey questionnaire

Adverse effects: A bruising 4/20, B bruising 4/20, rectal pain 1/20, erosion through rectal mucosa 2/20, type III hypersensitivity reaction 1/20 (requiring hospital care for 7 days, intravenous steroids, 10 week recovery period)

Number with >50% improvement in Wexner's score at 6 months: A 19/20, B 8/20 (not improved: A 1/20, B 12/20)

Number with >50% improvement in Wexner's score at 12 months: A 18/20, B 7/20 (not improved: A 2/20, B 13/20)

Wexner score at 6 months (mean (SD) N): 2.95 (1.7) 20, B 6.2 (2.69) 20

Wexner score at 12 months (mean (SD) N): 3.8 (2.76) 20, B 7 (2.77) 20

Faecal Incontinence Quality of Life index lifestyle at 6 months (mean (SD) N): A 3.68 (0.41) 20, B 3.12 (0.93) 20

Faecal Incontinence Quality of Life index lifestyle at 6 months (mean (SD) N): A 3.43 (0.33) 20, B 3.10 (0.86) 20

NotesPower calculation provided
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskCentral registry
Allocation concealment (selection bias)Low riskSealed envelopes
Blinding (performance bias and detection bias)
Participants
Low riskTreatment allocation blinded
Blinding (performance bias and detection bias)
Surgeons
High riskNot possible (different injection site)
Blinding (performance bias and detection bias)
Outcome assessors
Unclear riskNo data
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo drop-outs

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Dehli 2007A case-series study

Characteristics of ongoing studies [ordered by study ID]

Dehli 2009

Trial name or titleA randomized, controlled, clinical trial of biofeedback and anal injections as first treatment of fecal incontinence
MethodsTreatment, Randomised, Open Label, Active Control, Parallel Assignment, Efficacy Study
Participants 
InterventionsProcedure: Anal injection
Procedure: Biofeedback
OutcomesIncontinence measured by St.Marks incontinence score
Starting dateMay 2006
Contact information 
Notes 

Draganic 2008

Trial name or titlePTQ versus Durasphere in the treatment of faecal incontinence – a prospective study comparing two injectable bulking agents
MethodsRandomised controlled trial
ParticipantsPatients with faecal incontinence who, after discussion with a specialist, have opted to undergo treatment with an injectable bulking agent.
Interventions

Intervention: PTQ

Intervention: Durasphere

OutcomesPrimary: Wexner incontinence score, SF-36 quality of life score at 6 weeks post-procedure
Starting date1/05/2008
Contact informationDr Owen J Morris
NotesAccording to personal communication, the study is completed and the investigators are preparing for publication

EUCTR2010-021463-32-AT 2011

Trial name or titleSkeletal muscle-derived cell implantation for the treatment of fecal incontinence
MethodsMulticentre, randomised, double-blind, placebo controlled, parallel-group, dose-finding clinical study
Participants 
Interventions

Skeletal muscle-derived cells suspension for injection

Intervention: Concentration number 20000000-40000000

Intervention: Concentration number 70000000-110000000

OutcomesFrequency of incontinence episodes
Starting date24/02/2011
Contact informationPatientenanwaltschaft
NotesThis is a study for external sphincter injury

Michot 2012

Trial name or titleMyoblast for Anal Incontinence (MIAS)
MethodsRandomised, double-blind
Participants 
InterventionsIntervention: Myoblast injection
Intervention: saline solution injection
OutcomesImprovement of anal incontinence score, improvement of quality of life score
Starting dateJanuary 2012
Contact informationRouen University Hospital, Rouen, France, 76000
NotesThis is a study for external sphincter injury

NCT00762047 2009

Trial name or titleA prospective, multi-center, randomized, blinded study to evaluate durasphere FI for the treatment of fecal incontinence
MethodsRandomised, double-blind
ParticipantsFaecal incontinence in adult men and women. Planned to enroll 90 participants.
InterventionsIntervention: Durasphere FI
Intervention: Sham
Outcomes
  • The frequency and severity of fecal incontinence symptoms

  • Analysis of morbidity and complication rates associated with Durasphere.

  • The proportion of patients maintaining a 25% improvement in Cleveland Clinic Incontinence Score

Starting dateJune 2004
Contact informationhttp://clinicaltrials.gov/ct2/show/NCT00762047
NotesThe study appears to have been terminated in 2009, reason not stated - writing to trialists to find out more.

Norderval 2012

Trial name or titleTreatment of Fecal Incontinence After Obstetric Anal Sphincter Injuries (KISS)
MethodsRandomised, single-blinded (outcome assessor), efficacy study
Participants 
Interventions

Intervention: sacral nerve stimulation

Intervention: Permacol injection

OutcomesChange in St Marks incontinence score
Starting dateFebruary 2012
Contact informationMona B Rydningen
NotesThis is a study for external sphincter injury

Smart 2008

Trial name or titleA randomised controlled trial comparing the route of injection using Permacol (collagen)
MethodsRandomised
ParticipantsParticipants with (passive) faecal incontinence
InterventionsPermacol (collagen). Comparing one route of injection with another
Outcomes 
Starting date'Currently in progress' at February 2008
Contact informationThe two authors of the letter were based in Plymouth and Gateshead at the time of publication of their letter in 2008.
Notes 

Ancillary