CHIVA method for the treatment of chronic venous insufficiency

  • Review
  • Intervention

Authors

  • Sergi Bellmunt-Montoya,

    Corresponding author
    1. Hospital de la Santa Creu i Sant Pau, IBB Sant Pau, Angiology, Vascular and Endovascular Surgery, Barcelona, Spain
    • Sergi Bellmunt-Montoya, Angiology, Vascular and Endovascular Surgery, Hospital de la Santa Creu i Sant Pau, IBB Sant Pau, Sant Quinti No. 89, Barcelona, 08041, Spain. sbellmunt@santpau.cat.

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  • Jose Maria Escribano,

    1. Hospital Universitario Vall d'Hebron, Angiology, Vascular and Endovascular Surgery, Barcelona, Barcelona, Spain
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  • Jaume Dilme,

    1. Hospital de la Santa Creu i Sant Pau, IBB Sant Pau, Angiology, Vascular and Endovascular Surgery, Barcelona, Spain
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  • Maria José Martinez-Zapata

    1. CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Iberoamerican Cochrane Centre. Universitat Autònoma de Barcelona. Institute of Biomedical Research Sant Pau (IIB Sant Pau), Barcelona, Barcelona, Catalonia, Spain
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Abstract

Background

Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system.

Objectives

To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins.

Search methods

The Trials Search Co-ordinator of the Cochrane Peripheral Vascular Diseases Group searched the Specialised Register (November 2012), CENTRAL (2012, Issue 10) and clinical trials databases. The review authors searched PubMed and EMBASE (December 2012). There was no language restriction. We contacted study authors to obtain more information when necessary.

Selection criteria

We included randomized controlled trials (RCTs) that compared the CHIVA method versus any other treatments. Two review authors independently selected and evaluated the studies. One review author extracted data and performed the quantitative analysis.

Data collection and analysis

Two independent review authors extracted data from the selected papers. We calculated the risk ratio (RR), mean difference (MD), the number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI) using Review Manager 5.

Main results

We included four RCTs with 796 participants (70.5% women) from the 434 publications identified by the search strategy. Three RCTs compared the CHIVA method with vein stripping, and one RCT compared the CHIVA method with compression dressings in people with venous ulcers. We judged the methodological quality of the included studies as low to moderate. The overall risk of bias across studies was high because neither participants nor outcome assessors were blinded to the interventions. The primary endpoint, clinical recurrence, pooled between studies over a follow-up of 3 to 10 years, showed more favorable results for the CHIVA method than for vein stripping (721 people; RR 0.63; 95% CI 0.51 to 0.78; I2 = 0%, NNTB 6; 95% CI 4 to 10) or compression dressings (47 people; RR 0.23; 95% CI 0.06 to 0.96; NNTB 3; 95% CI 2 to 17). Only one study reported data on quality of life and these results presented graphically significantly favored the CHIVA method.

The vein stripping group had a higher risk of side effects than the CHIVA group; specifically, the RR for bruising was 0.63 (95% CI 0.53 to 0.76; NNTH 4; 95% CI 3 to 6) and the RR for nerve damage was 0.05 (95% CI 0.01 to 0.38; I2 = 0%; NNTH 12; 95% CI 9 to 20). There were no statistically significant differences between groups regarding the incidence of limb infection and superficial vein thrombosis.

Authors' conclusions

The CHIVA method reduces recurrence of varicose veins and produces fewer side effects than vein stripping. However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.

Plain language summary

CHIVA method for the treatment of varicose veins

Chronic venous insufficiency (CVI) is a disorder in which veins fail to pump blood back to the heart adequately. It can cause varicose veins, skin ulcers, and superficial or deep vein thrombosis in the legs. The ambulatory conservative hemodynamic correction of venous insufficiency (CHIVA) method is a minimally invasive surgical technique to treat varicose veins. The aim of the CHIVA treatment is to eliminate the venous-venous shunts by disconnecting the escape points, preserving the saphenous vein and normal venous drainage of the superficial tissues of the limb. This review evaluated the effectiveness and safety of the CHIVA method in CVI and included four randomized controlled trials with 796 participants. The results showed that the CHIVA method reduced recurrence of varicose veins and produced less bruising and nerve damage than vein stripping. However, studies are needed to confirm these conclusions since they are based on clinical trials with methodological limitations such as high risk of bias mainly because participants and outcome assessors were not blinded to the interventions.

Summary of findings(Explanation)

Summary of findings for the main comparison. 
  1. 1 The studies were open: participants and assessors knew the intervention.

    2 The study was open: participants and assessors knew the intervention.

    3 There was imprecision due to low number of events.

    4 CHIVA method is unlikely to cause nerve damage. We have upgraded the quality of evidence for the large effect.

    5 Assumed risk is mean baseline risk from study population.

    6 Assumed risk is the median control group risk from studies on meta-analysis

CHIVA compared with stripping for varicose veins

Patient or population: adults with varicose veins

Settings: hospital

Intervention: CHIVA

Comparison: stripping

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
StrippingCHIVA

Recurrence of varicose veins

(follow-up: 60 months - 10 years)

Study population

RR 0.63

(0.51 to 0.78)

721
(3 studies)
⊕⊕⊕⊝
moderate1
 
471 per 1000 297 per 1000
(240 to 368)
Moderate6
383 per 1000 241 per 1000
(195 to 299)

Side effects - bruises

(follow-up: 60 months)

Study population5

RR 0.63

(0.53 to 0.76)

501
(1 study)
⊕⊕⊕⊝
moderate2
 
719 per 1000 453 per 1000
(381 to 546)

Side effects - limb infection

(follow-up: 60 months)

Study population5

RR 1.33

(0.38 to 4.66)

501
(1 study)
⊕⊕⊝⊝2,3
low
 
18 per 1000 24 per 1000
(7 to 84)

Side effects - superficial vein thrombosis

(follow-up: 60 months - 5 years)

Study population

RR 2.23

(0.6 to 8.33)

601
(2 studies)
⊕⊕⊝⊝1,3
low
 
10 per 1000 23 per 1000
(6 to 83)
Moderate6
6 per 1000 13 per 1000
(4 to 50)

Side effects - nerve damage

(follow-up: 60 months - 5 years)

Study population

RR 0.05

(0.01 to 0.38)

601
(2 studies)
⊕⊕⊕⊝1,3,4
moderate
 
68 per 1000 3 per 1000
(1 to 26)
Moderate6
135 per 1000 7 per 1000
(1 to 51)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

Chronic venous insufficiency (CVI) is a complex condition in which the veins do not efficiently return blood from the legs to the heart. CVI develops slowly and its complications often appear years or even decades after the onset of symptoms (Kurz 1999). Its origin is multifactorial and clinical manifestations are widely varied, ranging from dilated cutaneous veins and varicose veins, to edema, skin discoloration, and ulcers in advanced cases. The most common symptoms are pain, fatigue, heaviness, warmth and swelling of the leg, all of which are more intense when standing and under environmental conditions of heat and humidity (Vanhouette 1997). CVI can affect the superficial venous system or the deep venous system, or both, but the most common situation is involvement of the superficial venous system, the main manifestation of which is varicose veins (Table 1; Porter 1995). 

Table 1. CEAP clinical classification (C)
  1. See Porter 1995.

Class Clinical indication
0No visible or palpable signs of venous disease
1Telangiectases or reticular veins
2Varicose veins
3Edema
4Skin changes ascribed to venous disease (e.g. pigmentation, venous eczema, lipodermatosclerosis)
5Skin changes as defined here with healed ulceration
6Skin changes as defined here with active ulceration

The estimated prevalence of CVI varies depending on the criteria used. On the basis of varicose veins in the physical examination, prevalence has been estimated to range from 30% to 40% in the general adult population (Lee 2003), and to affect up to 50% of women (Carpentier 2004). If we consider the detection of reflux in the superficial venous system by hemodynamic study, prevalence can range from 9% in males to 15% in females (Allan 2000).                                                                                           

Treatment options for CVI have advanced greatly in recent years and involve both medical and surgical methods. The choice of therapy depends on the stage of development of the disease (Agus 2001), and options are often used in combination. Treatment of CVI in general and specific treatments for varicose veins do not cure the disease but they can prevent complications and improve signs and symptoms, even healing of ulcers in some cases. General treatment for CVI includes hygienic and postural measures (such as elevation of the legs or walking around to keep the muscle pump working) (Hamdan 2012), compression therapy (Nelson 2000; Nelson 2011; O'Meara 2009), topical treatment (Aziz 2011; Cullum 2010; Jull 2008; Kranke 2004; O'Meara 2010; Palfreyman 2006), and drug therapy (Martinez-Zapata 2005; O'Meara 2010). Specific treatment for varicose veins includes sclerotherapy (Tisi 2006), laser therapy (Flemming 1999), radiofrequency ablation (Nesbitt 2011), and surgery (Rigby 2004).

Surgical treatment for varicose veins dates back to the early 20th century when Keller described removal of the saphenous vein through a metal loop in 1905 (Keller 1905) and Lofgren described endoluminal stripping in 1906 (Lofgren 1977). Two years later, Babcock used a vein-extractor similar to that used today (Lofgren 1977). In 1966, Muller described ambulatory phlebectomy (Muller 1966). Such techniques, however, cannot totally prevent varicose vein recurrence (Blomgren 2004; Labropoulos 2005; Perrin 2000; Winterborn 2004), or remodeling of the venous network of subcutaneous tissue (Juan 2002).

The introduction of duplex scanning in the study of CVI has provided in vivo knowledge of venous hemodynamics (Franceschi 1988). It not only enables a complete morphological study, but also allows mapping of the hemodynamics of the venous system, providing precise information on any changes or abnormalities (Cavezzi 2007; Coleridge-Smith 2006; Labropoulos 2001; Labropoulos 2005; Nicolaides 2000).

Description of the intervention

In 1988, Franceschi described a procedure for the treatment of varicose veins based on venous hemodynamics with preservation of the superficial venous system. He named this procedure ambulatory conservative hemodynamic correction of venous insufficiency (cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire (CHIVA)) (Franceschi 1997).

CHIVA can be performed via open surgery or via endovascular procedures such as laser, radiofrequency or sclerotherapy. It is based on modifying the hemodynamics of the venous system to eliminate varicose dilations and to preserve the saphenous vein. Findings showing that CHIVA decreases the diameter of the saphenous vein (from 2.6 to 1.6 mm) and the femoral vein (from 0.7 to 0.4 mm) have supported this theory (Escribano 2003; Mendoza 2011).

How the intervention might work

The physiological route of venous blood is an anterograde circuit, draining from the superficial venous system to the deep venous system, and finally, to the heart. Primary varicose veins are characterized by a retrograde circuit or a venous-venous shunt (Goren 1996). This abnormal circuit consists of a retrograde proximal reflux point (escape point) from which blood from the deep venous system is discharged into the superficial venous system, usually the saphenous veins. This pathological situation is caused by the dysfunction of the valves of the veins. The accumulation of blood in the veins causes a hydrostatic pressure column between the escape point and the point of re-entry into the deep venous system, and it generally comprises the saphenous vein and the perforating re-entry vein. This blood in the deep venous system can re-enter the superficial venous system. This closed circuit is the venous-venous shunt.

The aim of the CHIVA treatment is to eliminate the venous-venous shunts by disconnecting the escape points, preserving the saphenous vein and normal venous drainage of the superficial tissues of the limb. The CHIVA method is a minimally invasive surgical procedure, usually performed under local anesthesia, based on the findings of a careful analysis of the hemodynamic superficial venous network by duplex ultrasound. The principles underlying the CHIVA method are fragmentation of the venous pressure column, disconnection of venous-venous shunts, preservation of the re-entry perforators and abolition of undrained superficial varicose veins. Fragmentation of the venous pressure column and disconnection of venous-venous shunts is generally implemented by open surgery, but sclerotherapy, laser or radiofrequency can also be used.

Why it is important to do this review

CHIVA is one of the most widely used methods in several countries and is one of the few strategies that treat varicose veins without seeking their destruction.

Objectives

To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins.

Methods

Criteria for considering studies for this review

Types of studies

Randomized controlled trials (RCTs).

Types of participants

Men and women over 18 years of age with varicose veins at clinical stage C2-C6 of the CEAP (clinical, etiology, anatomy, pathophysiology) classification (Porter 1995) (Table 1).

Types of interventions

RCTs that assess the CHIVA method compared with other procedures to treat varicose veins, such as drugs, sclerotherapy, compressive dressings and other surgical methods.

Types of outcome measures

Primary outcomes

Recurrence of varicose veins was defined as the detection of new varicose veins by clinical or ultrasound evaluation after a minimum follow-up of one year.

Secondary outcomes

1. Re-treatment or reintervention, defined as the need for a second intervention due to recurrence of varicose veins or new varicose veins in the same leg and the same area.

2. Clinical or esthetic changes after a minimum follow-up of one month after the intervention, assessed by the following:  

  • Objective signs:

    • free from reflux, as defined by reverse flow from the deep venous system to the superficial venous system, and checked by duplex ultrasound;

    • edema, measured by the dichotomous variable edema and the continuous variables 'ankle perimeter circumference' and 'volume of the leg';

    • skin manifestations, such as venous ulcers and trophic alterations, which may include telangiectasia (small red points on the skin caused by permanently opened tiny blood vessels), reticular veins (dilated veins that show as a net-like pattern on the skin), varicose veins (permanently dilated veins) or lipodermatosclerosis (a hardening of the skin that may gain a red or brown pigmentation and is accompanied by wasting of the subcutaneous fat).

  • Subjective symptoms:

    • pain;

    • cramps;

    • restless legs;

    • itching;

    • feeling of heaviness in the legs;

    • swelling;

    • paresthesias (abnormal sensations, such as prickling, burning, tingling).

  • Global assessment measures:

    • disease-specific quality of life (QoL) scales (e.g. CVIIQ or Veines-QoL) or satisfaction of participants, or both.

3. Side effects

including hematoma, infection, superficial or deep venous thrombosis, lung embolism and nerve injury.

Search methods for identification of studies

There was no language restriction.

Electronic searches

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and the Cochrane Central Register of Controlled Trials (CENTRAL) 2012, Issue 10. See Appendix 1 for details of the search strategy used to search CENTRAL. The TSC maintains the Specialised Register, which is constructed from weekly electronic searches of MEDLINE, EMBASE, CINAHL, and AMED, and through handsearching relevant journals. The Specialised Register section of the Cochrane Peripheral Vascular Diseases Group module in The Cochrane Library (www.thecochranelibrary.com) provides the full list of the databases, journals and conference proceedings that have been searched, as well as the search strategies used.

The TSC searched the following trial databases for details of ongoing and unpublished studies (November 2012) using the terms c.h.i.v.a. or chiva:

In addition, the review authors searched EMBASE (Ovid platform; last searched December 2012) and PubMed (last searched December 2012) using the search strategies given in Appendix 2 and Appendix 3.

Searching other resources

We scrutinized reference lists of identified RCTs, systematic reviews and meta-analyses to find further trials. We contacted trial authors for additional information.

Data collection and analysis

Selection of studies

Two review authors (SB and MJM) independently assessed the eligibility of the studies identified in the search. We classified eligible studies as included or excluded. In cases of disagreements, a third review author would have independently evaluated the study and discussed it with the rest of the team. However, it was not necessary, as there were no disagreements.

Data extraction and management

Two review authors (SB and MJM) collected data independently on a previously tested standardized form. Data included methodological quality, characteristics of study participants, characteristics of the intervention and control groups, and outcome characteristics of each group of participants. One review author (MJM) entered the data into Review Manager 5.1 and performed the appropriate analyses (RevMan 2011).

Assessment of risk of bias in included studies

Two review authors (SB and MJM) assessed the quality of the studies, examining the randomization method (sequence generation and allocation concealment). They also assessed the blinding of participants and investigators (caregivers and outcome assessors), the completeness of outcome data and the percentage of participants lost to follow-up.

Once this information was gathered, the authors classified each study into low, unclear or high risk of bias, based on the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We also specified whether the studies calculated the sample size needed and whether they included an intention-to-treat (ITT) analysis.

Measures of treatment effect

For each study, we calculated risk ratios (RR) for dichotomous variables and mean differences (MD) for continuous variables with 95% confidence intervals (CI). If the continuous variables in the studies were measured using different scales, we calculated the standardized mean difference (SMD) and 95% CIs. We also calculated the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) with 95% CIs.

Unit of analysis issues

The unit of analysis was the individual participant.

Dealing with missing data

We contacted study authors to obtain additional information.

The main analysis was an 'available-case analysis', analyzing data as provided in the individual studies.

Assessment of heterogeneity

We examined the characteristics of each study to determine clinical heterogeneity. We deemed an I2 statistic greater than 50% as substantial heterogeneity. We also studied the sources of heterogeneity.

Assessment of reporting biases

We did not perform a funnel plot to assess reporting bias because we included fewer than 10 studies (Sterne 2011).

Data synthesis

We estimated the global effect for each variable through a meta-analysis. We applied the statistical method of Mantel-Haenszel for dichotomous measures and the inverse variance for continuous measures, using a fixed-effect model. When I2 was greater than 50%, we used a random-effects model. If heterogeneity was greater than 75%, we did not pool the results. We performed all statistical analyses using Review Manager 5 (RevMan 2011). We calculated the NNTB and NNTH, and the corresponding 95% CI.

Subgroup analysis and investigation of heterogeneity

We considered two sources of clinical heterogeneity to plan subgroup analysis if necessary.

  1. Type of procedure used to implement the CHIVA method: open surgery, sclerotherapy, laser, radiofrequency and any other.

  2. Type of comparison assessed: CHIVA versus drugs, compression dressings or other techniques.

Sensitivity analysis

We conducted a sensitivity analysis to assess the strength of the results and to explain possible heterogeneity between the studies. We re-analyzed the data by ITT, and imputed data using the worst-case scenario, that is, imputed missing values for participants who withdrew or were lost to follow-up as negative events in the experimental group and as positive events in the control group.

We did not conduct a sensitivity analyses by comparing any unpublished studies with published studies or by comparing studies with high risk of bias with those having low risk of bias due to lack of suitable data.

Results

Description of studies

See Figure 1.

Figure 1.

Study flow diagram.

Results of the search

The search identified 434 citations. After considering titles and abstracts, we retrieved 15 potentially relevant papers in full text. Finally, after reading the full text, we included 10 papers reporting four RCTs. Three studies compared CHIVA with the stripping technique (Carandina 2008; Iborra-Ortega 2006; Pares 2010) and one compared CHIVA with the use of compression dressings (Zamboni 2003) (see Characteristics of included studies table). We excluded the remaining five studies (Figure 1) (see Characteristics of excluded studies table).

We contacted three study authors because more information was needed and to clarify doubts regarding missing data (Iborra-Ortega 2006; Pares 2010; Zamboni 2003).

Included studies

Four included RCTs recruited 796 participants (70.5% women) aged 47 to 63 years (Carandina 2008; Iborra-Ortega 2006; Pares 2010; Zamboni 2003) (see Characteristics of included studies table).

All participants had CVI and a clinical stage of the CEAP classification between 2 and 6. The study of Iborra-Ortega 2006 included only people with CEAP 2, whereas the study of Zamboni 2003 included only people with venous ulcers and CEAP 6 (Table 1). Follow-up of participants also varied between studies, with a minimum of three years (Zamboni 2003) and a maximum of 10 years (Carandina 2008). Three studies compared CHIVA method with stripping (Carandina 2008; Iborra-Ortega 2006; Pares 2010) and one study compared CHIVA with compression dressings (Zamboni 2003). In all included studies, open surgery was used to implement the CHIVA method.

With the exception of Pares 2010, the studies did not specify sample size calculation.

The funding sources was public in three studies (Iborra-Ortega 2006; Pares 2010; Zamboni 2003), and not specified in the other (Carandina 2008).

Excluded studies

In total, we excluded five studies (see Characteristics of excluded studies table); four controlled studies were not randomized (Maeso 2001; Solis 2009; Zamboni 1995; Zamboni 1998) and one study was not controlled (Zamboni 1996).

Risk of bias in included studies

Overall, methodological quality of the studies included in this review was low to moderate (Summary of findings for the main comparison). The risk of bias was generally high, mainly because participants and outcome assessors were not blinded to the interventions (Figure 2; Figure 3).

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

All studies adequately explained how the randomization sequence was generated. Only two of the four studies specified allocation concealment (Carandina 2008; Iborra-Ortega 2006). We contacted the other two study authors and they provided this information (Pares 2010; Zamboni 2003). Three studies specified that allocation was done by telephone (Iborra-Ortega 2006; Pares 2010; Zamboni 2003). In the Carandina 2008 study, allocation was blinded to the treating physicians, but it did not state how the blinding was done.

Blinding

Studies could not be blinded because the specific anatomical changes produced by the intervention were easily recognizable by a specialist. In one study, independent assessors evaluated the clinical results in an attempt to compensate for this bias (Carandina 2008).

Incomplete outcome data

The percentage of participants lost to follow-up was less than 10% in both groups in three of the studies (Iborra-Ortega 2006; Pares 2010; Zamboni 2003), and in the intervention group in the fourth study (Carandina 2008). However, in the conventional surgery group of the Carandina 2008 study the percentage of losses was 28%.

Selective reporting

In the study of Zamboni 2003, it is not clear if recurrence data were based on ultrasound or clinical parameters. Data about ulcer healing time were incomplete and were not included in this review.

Effects of interventions

See: Summary of findings for the main comparison

We identified only studies comparing CHIVA with vein stripping and with compression dressings.

Comparison of vein stripping versus the CHIVA method

We identified three RCTs that compared vein stripping versus CHIVA (Carandina 2008; Iborra-Ortega 2006; Pares 2010).

Primary outcome
Recurrence of varicose veins

These three studies included 721 participants. The pooled result was significant and favored the CHIVA method (RR 0.63; 95% CI 0.51 to 0.78; I2 = 0%; NNTB 6; 95% CI 4 to 10) (Figure 4).

Figure 4.

Forest plot of comparison: 1 CHIVA versus stripping, outcome: 1.1 Recurrence of varicose veins.

The sensitivity analysis comparing published studies versus non-published was not performed because all three studies were published. We did not analyze sensitivity based on the level of risk of bias because all studies had a high risk of bias. None of the studies masked the interventions.

The sensitivity analysis by ITT included 751 people and also favored CHIVA (pooled RR 0.73; 95% CI 0.60 to 0.89; I2 = 25%).

Secondary outcomes
Re-treatment

Only the Iborra-Ortega 2006 study reported data about re-interventions after a five-year follow-up. Five participants in each treatment group underwent re-intervention (RR 0.96; 95% CI 0.30 to 3.11).

Clinical or esthetic changes
  • Objective signs:

  1. "Free from reflux", checked by echo-Doppler (two studies; Carandina 2008; Pares 2010). They had a combined total of 625 participants but their data were not pooled due to the high heterogeneity (I2 = 76%). However, in both studies the results significantly favored the CHIVA method.

  2. "Edema" was not reported in the included studies.

  3. "Aesthetic improvement reported by the patient" was reported in the Iborra-Ortega 2006 study as a dichotomous outcome. There were no significant differences between the interventions at five-year follow-up (RR 1.03; 95% CI 0.90 to 1.18). In the Carandina 2008 study with 124 participants, "aesthetic improvement reported by the patient" was described as a continuous outcome. There were no significant differences between the interventions at 10-year follow-up (MD -0.16; 95% CI -2.66 to 2.34). "Aesthetic improvement reported by the investigator" was reported in the Iborra-Ortega 2006 study as a dichotomous outcome. There were no significant differences between the interventions at five-year follow-up (RR 1.12; 95% CI 0.85 to 1.48).

  • Subjective symptoms:

None of the three studies specifically measured subjective symptoms. Related outcomes were:

  1. Iborra-Ortega 2006 and Pares 2010 reported "Cure or no clinical symptoms" in 601 participants. The pooled data significantly favored the CHIVA method (RR 1.73; 95% CI 1.36 to 2.19; I2 = 0%).

  2. Iborra-Ortega 2006 and Pares 2010 assessed "Clinical improvement" in 601 participants. The pooled data were not significantly different (RR 0.93; 95% CI 0.71 to 1.21; I2 = 0%).

  • Global assessment measures:

None of the included trials provided information on QoL or participant satisfaction.

Side effects

Iborra-Ortega 2006 and Pares 2010 provided information in 601 participants (Figure 5).  

Figure 5.

Forest plot of comparison: 1 CHIVA versus stripping, outcome: 1.9 Side effects.

Pares 2010 included information on "Bruises". The CHIVA method reduced the number of participants with bruises compared with stripping (RR 0.63; 95% CI 0.53 to 0.76; NNTH 4; 95% CI 3 to 6). This study also reported information on "Limb infection", finding no significant differences between groups (RR 1.33; 95% CI 0.38 to 4.66).

Iborra-Ortega 2006 and Pares 2010 included information on "Superficial vein thrombosis". The pooled result was not significant (RR 2.23; 95% CI 0.60 to 8.33; I2 = 42%). The same two studies reported data on "Nerve damage". The pooled result was significant and favored the CHIVA method (RR 0.05; 95% CI 0.01 to 0.38; I2 = 0%; NNTH 12; 95% CI 9 to 20).

Comparison of compression dressing versus the CHIVA method

One RCT included only participants with venous ulcers. This study compared compression with the CHIVA method in 47 people (Zamboni 2003). The unit of analysis was the ulcer and not the individual, but the data were analyzed because, except for one person, all participants had only one ulcer. The result of the outcome "Recurrence of venous ulcer" significantly favored the CHIVA method (RR 0.23; 95% CI 0.06 to 0.96; NNTH 3; 95% CI 2 to 17). "Cure of venous ulcer" showed no significant differences (RR 1.04; 95% CI 0.93 to 1.17).

The Zamboni 2003 study assessed "Quality of life" measured by the Short Form-36 (SF-36) questionnaire, but there were no numerical data presented in the paper. The median score differences (end of observation minus baseline) for the eight domains of SF-36 questionnaire were shown in a Kaplan -Meier graph only. The authors concluded that the CHIVA method significantly improved the QoL after a three-year follow-up.

Subgroup analysis

All four included studies implemented the CHIVA method by open surgery. Therefore, we did not need to perform a subgroup analysis according to the procedure used to implement the CHIVA method.

Discussion

Summary of main results

This systematic review included four RCTs. All included studies assessed the CHIVA method implemented by open surgery. Three of the four trials compared the CHIVA method with vein stripping for varicose veins, and one compared the CHIVA method with compression for venous ulcers. The results showed that the CHIVA method reduced recurrence of varicose veins compared to other methods. However, no differences in clinical improvement or cosmetic results, as perceived by participants and investigators, were detected between groups. Quality of life was only assessed in the Zamboni 2003 study and the results favored the CHIVA method.

Regarding adverse effects, the CHIVA method showed a lower percentage of bruising and nerve injuries than vein stripping. The risk-benefit balance therefore favored the CHIVA method over vein stripping.

Overall completeness and applicability of evidence

We have included all relevant studies that assessed the CHIVA method for treatment of varicose veins in adults. The studies were conducted in Italy and Spain, where the CHIVA method is frequently used (Milone 2011). However, new publications show this method is implemented or considered in other countries such as Taiwan, Switzerland and the USA (Chan 2011; Mendoza 2011; Mowatt-Larssen 2012).

All participants had venous reflux and the severity of the chronic venous disease was variable, ranging from esthetic alterations to leg ulcers. Three studies compared the CHIVA method implemented by open surgery with vein stripping and only one RCT with 47 participants compared the CHIVA method implemented by open surgery with compression for venous ulcers.

We did not identify any studies that compared the CHIVA method with other surgical approaches such as sclerotherapy, laser or radiofrequency. Evidence, therefore, is limited to the comparison of the CHIVA method implemented by open surgery versus stripping or compression.

All studies included the primary outcome 'recurrence'. The length of follow-up, from 3 to 10 years, was sufficient to assess recurrence and adverse effects adequately.

Quality of the evidence

Overall, methodological quality of the studies included in this review was low to moderate. The global risk of bias was high because participants and investigators were not blinded to interventions. Blinded assessment is not possible in clinical trials that assess vein surgery because the intervention has characteristic anatomical consequences.

Potential biases in the review process

The methodological process of our review was rigorous. The search strategy was thorough without language restrictions. We contacted the main authors of included studies for further information. All trials included in the review were funded either by public organizations or non-profit institutions. No conflicts of interest were declared.

Agreements and disagreements with other studies or reviews

Although one narrative review on the CHIVA method has been published (Mendoza 2008), we found no record of any review with pooled results. Mendoza 2008 included randomized and non-randomized clinical trials. The conclusions were that the CHIVA method improved subjective and objective outcomes better or equal to stripping, and had lower rate of recurrence and cost.

Authors' conclusions

Implications for practice

  • The CHIVA method appears to result in fewer complications and recurrences than traditional open surgery by stripping. However, there were no data comparing this method to the newer minimally invasive endovenous techniques. CHIVA is an appropriate treatment for varicose veins, although further studies are needed because the results are based on few studies with the methodological quality of the included studies judged to be low to moderate.

Implications for research

  • Randomized controlled trials are needed to corroborate the findings reported in this review as they are based on few studies with the methodological quality of the included studies judged to be low to moderate. Quality of life should be included as an outcome of interest in order to measure, with a standardized instrument, the patient satisfaction of the intervention. It could also be of interest to compare the CHIVA method with surgical approaches other than open surgery.

Acknowledgements

The authors would like to acknowledge the contribution of the Trials Search Co-ordinator (Karen Welch) for running searches, Managing Editor (Marlene Stewart), peer reviewers, editors of the Cochrane Peripheral Vascular Diseases Group for their comments on the protocol and review, and Carolyn Newey for their help in editing the manuscript.

Data and analyses

Download statistical data

Comparison 1. CHIVA versus stripping
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Recurrence of varicose veins3721Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.51, 0.78]
2 Re-treatment1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
3 Free from reflux2 Risk Ratio (M-H, Random, 95% CI)Totals not selected
4 Esthetic improvement assessed by the participant1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
5 Esthetic improvement assessed by the participant1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
6 Esthetic improvement assessed by the investigator1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
7 Cure or no clinical symptoms2601Risk Ratio (M-H, Fixed, 95% CI)1.73 [1.36, 2.19]
8 Clinical improvement2601Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.71, 1.21]
9 Side effects2 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
9.1 Bruises1501Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.53, 0.76]
9.2 Limb infection1501Risk Ratio (M-H, Fixed, 95% CI)1.33 [0.38, 4.66]
9.3 Superficial vein trombosis2601Risk Ratio (M-H, Fixed, 95% CI)2.23 [0.60, 8.33]
9.4 Nerve damage2601Risk Ratio (M-H, Fixed, 95% CI)0.05 [0.01, 0.38]
10 Recurrence of varicose veins. Sensitivity analysis.3751Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.60, 0.89]
10.1 Intention-to-treat3751Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.60, 0.89]
Analysis 1.1.

Comparison 1 CHIVA versus stripping, Outcome 1 Recurrence of varicose veins.

Analysis 1.2.

Comparison 1 CHIVA versus stripping, Outcome 2 Re-treatment.

Analysis 1.3.

Comparison 1 CHIVA versus stripping, Outcome 3 Free from reflux.

Analysis 1.4.

Comparison 1 CHIVA versus stripping, Outcome 4 Esthetic improvement assessed by the participant.

Analysis 1.5.

Comparison 1 CHIVA versus stripping, Outcome 5 Esthetic improvement assessed by the participant.

Analysis 1.6.

Comparison 1 CHIVA versus stripping, Outcome 6 Esthetic improvement assessed by the investigator.

Analysis 1.7.

Comparison 1 CHIVA versus stripping, Outcome 7 Cure or no clinical symptoms.

Analysis 1.8.

Comparison 1 CHIVA versus stripping, Outcome 8 Clinical improvement.

Analysis 1.9.

Comparison 1 CHIVA versus stripping, Outcome 9 Side effects.

Analysis 1.10.

Comparison 1 CHIVA versus stripping, Outcome 10 Recurrence of varicose veins. Sensitivity analysis..

Comparison 2. CHIVA versus compression dressing
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Recurrence of venous ulcer1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
2 Cure of venous ulcer1 Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
Analysis 2.1.

Comparison 2 CHIVA versus compression dressing, Outcome 1 Recurrence of venous ulcer.

Analysis 2.2.

Comparison 2 CHIVA versus compression dressing, Outcome 2 Cure of venous ulcer.

Appendices

Appendix 1. CENTRAL search strategy

#1MeSH descriptor: [Varicose Veins] explode all trees742
#2(varicos* near/3 (vein* or veno*))766
#3(tortu* near/3 (vein* or veno*))14
#4(incomp* near/3 (vein* or veno* or saphenous or valv*))133
#5(insuffic* near/3 (vein* or veno* or saphenous))706
#6((saphenous or vein* or veno*) near/3 reflux)99
#7MeSH descriptor: [Saphenous Vein] this term only and with qualifiers: [Surgery - SU]349
#8GSV78
#9MeSH descriptor: [Venous Insufficiency] explode all trees341
#10(#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9)1877
#11(CHIVA or C.H.I.V.A):ti,ab,kw9
#12MeSH descriptor: [Ambulatory Surgical Procedures] this term only1384
#13MeSH descriptor: [Surgical Procedures, Minimally Invasive] this term only718
#14MeSH descriptor: [Vascular Surgical Procedures] this term only619
#15MeSH descriptor: [Hemodynamics] explode all trees39923
#16haemodynamic or hemodynamic:ti,ab,kw10987
#17(ambulat*):ti,ab,kw12674
#18#11 or #12 or #13 or #14 or #15 or #16 or #1755898
#19#10 and #18 in Trials (Word variations have been searched)282

Appendix 2. Authors' EMBASE search strategy

#1exp varicosis/46688
#2varicose vein*.mp8645
#3varice*.mp46202
#41 or 2 or 371685
#5CHIVA.mp123
#6Conservative Hemodynamic Management of Varicose Vein*.mp3
#7Conservative Hemodynamic Management.mp4
#7hemodynamic correction.mp84
#95 or 6 or 7 or 8202
#104 and 987

Appendix 3. Authors' PubMed search strategy

#1 "Varicose Veins"[MeSH]14337
#2varicose vein*[tw]12772
#3varice*[tw]28511
#4((#1) OR #2) OR #342070
#5CHIVA[tw]50
#6Conservative Haemodynamic Management of Varicose Vein*[tw]7
#7Conservative Hemodynamic Management of Varicose Vein*[tw]7
#7Conservative Hemodynamic Management[tw]3
#9Conservative Haemodynamic Management[tw]0
#10hemodynamic correction[tw]56
#11haemodynamic correction[tw]9
#12((((((#5) OR #6) OR #7) OR #8) OR #9) OR #10) OR #11110
#13(#4) AND #1243

Contributions of authors

Conceiving the review: SB, JME
Designing the review: SB, MJM
Co-ordinating the review: MJM
Designing electronic search strategy: Cochrane Peripheral Vascular Diseases Group editorial base
Screening search results: SB, MJM
Obtaining copies of trials: SB, MJM
Appraising quality of papers: SB, MJM
Abstracting data from papers: SB, MJM
Data management for the review: MJM
Entering data into RevMan: MJM
Analysis of data: MJM
Interpretation of data: all authors
Writing the review: MJM, SB, JME
Draft the final review: all authors
Guarantor for the review: SB, MJM

Declarations of interest

Associazione "Umanizazione" della Chirurgia (Italy) financed the review; money was paid to the institution of author Dr. Maria José Martinez-Zapata.

Dr Sergi Bellmunt-Montoya reports a secondary conflict of interest resulting from consultancy payments from Sanofi-Aventis and Otsuka/Ferrer for activities not related to this review.

Sources of support

Internal sources

  • Iberoamerican Cochrane Center, Spain.

External sources

  • Chief Scientist Office, Scottish Government Health Directorates, Scottish Government, UK.

    The PVD Group editorial base is supported by the Chief Scientist Office.

  • Associazione "Umanizazione" della Chirurgia, Italy.

    This is a not-for-profit organization that promotes formative and scientific sessions (scientific meetings, workshops, etc.) principally in relation to venous hemodynamics of the lower limbs. This organization partially finances this review because it has an interest in the independent assessment of the CHIVA method but it does not have influence on the review process.

Differences between protocol and review

The title has been changed from "CHIVA method for the treatment of varicose veins" to "CHIVA method for the treatment of chronic venous insufficiency". 

The name of the primary outcome "Recurrence of varicosity" has been changed to "Recurrence of varicose veins". Varicosity and varicose veins have the same meaning, but varicose veins is the most commonly used term.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Carandina 2008

Methods

Design: randomized controlled trial

Number of participating centers: 1

Setting: hospital

Country: Italy

Unit of randomization: participant

Unit of analysis: participant

Follow-up: participants were reviewed postoperatively at 1, 6, 12 months, and subsequently, after 3 and 10 years

Participants

Number of participants: 150 (75 surgery and 75 CHIVA)

Sex: 33 men and 91 women

Age (mean): 48-50 years

Inclusion criteria: primary chronic venous insufficiency with no history of surgery or sclerotherapy, presence of saphenofemoral reflux and incompetence of the saphenous trunk, presence of a competent deep venous system, at least 1 re-entry perforator located in the trunk of the saphenous and 1 or more veins and incompetent tributaries of the great saphenous vein

Exclusion criteria: aged ≥ 70 years, people with deficiency of the calf muscle pump or unable to walk; people with diabetes, autoimmune diseases, malignancies, severe kidney disease, liver disease, cardio-respiratory disease, or previous history of deep vein thrombosis

Interventions

1) Stripping procedure: saphenofemoral ligation, great saphenous vein stripping from groin to knee, multiple phlebectomies of the tributaries and subfascial ligation of thigh perforating veins

2) CHIVA: saphenofemoral ligation, disconnection from the great saphenous vein of the varicose tributaries and their avulsion through cosmetic incisions

Postoperative management: people treated with CHIVA wore class 2 medical compression stockings above the knee for 3 weeks. Limbs that had been treated by saphenous stripping were bandaged to minimize bruising. Bandages were replaced with class 2 medical compression stockings above the knee after 1-3 days and then worn for 14 days. Study participants were usually discharged from hospital on the day of surgery

Outcomes

Primary outcome: recurrence of varicose veins at 10 years of follow-up. Recurrence was defined as class C or D of the Hobbs' score (Hobbs 1974) (Table 2) and the presence of reflux on duplex ultrasonography with a demonstrable escape point

Secondary outcome: functional or cosmetic results

Both clinical and ultrasound examinations were performed at each visit

Clinical assessment of surgical results: 3 independent assessors, who had not been involved in previous surgical decision making and operative procedures, examined all limbs. They assigned a score to each limb according to the method reported by Hobbs. Subsequently, participants were further analyzed by duplex scanning using a standard methodology. Functional and cosmetic results were self assessed by the participants at the time of the last examination in hospital

Assessment of recurrences: were considered varicose veins recurrence if:

1) the remaining or newly formed varicose veins had a diameter > 5 mm and the presence of incompetent main trunks and perforator (Hobbs' score C and D)

2) there was presence of reflux, as measured by duplex ultrasonography, with a demonstrable escape point and change of venous network

NotesSample size was specified in the 'methods' section
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "Study randomisation was by a computer-generated randomisation list of the 150 patients, structured in balanced blocks of 4 patients and blinded to the treating physicians. The allocated treatment was disclosed shortly before surgical treatment and patients were treated with saphenous stripping or CHIVA, 75 patients by each technique"

Comment: study randomization was by a computer-generated randomization list, structured in balanced blocks

Allocation concealment (selection bias)Low risk

Quote: "Study randomisation was by a computer-generated randomisation list of the 150 patients, structured in balanced blocks of 4 patients and blinded to the treating physicians. The allocated treatment was disclosed shortly before surgical treatment and patients were treated with saphenous stripping or CHIVA, 75 patients by each technique"

Comment: allocation was blinded to the treating physicians. The allocated treatment was disclosed shortly before surgical treatment

Blinding of participants and personnel (performance bias)
All outcomes (participants)
Unclear riskIt is not specified if the participants were blinded
Blinding of participants and personnel (performance bias)
All outcomes (personnel)
High riskThe surgeon that applied the intervention was unblinded
Blinding of outcome assessment (detection bias)
All outcomes
Low risk

Quote: "At the time of scoring the surgical outcome the assessors were unaware of the procedure each patient"

Comment: the assessor was blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskThere were 26 (17.3%) participants lost in 10 years of follow-up, with no differences between groups. The reasons for losses were not specified
Selective reporting (reporting bias)Low riskThe results of all outcomes prespecified in the methods of the trial report were presented. The trial protocol was not requested from the study authors

Iborra-Ortega 2006

Methods

Design: randomized controlled trial

Number of participating centers: 1

Setting: hospital

Country: Spain

Unit of randomization: participant

Unit of analysis: participant.

Follow-up: first week after surgery; 1, 3, and 6 months; and thereafter annually to 5 years

Participants

Number of participants: 100 (49 stripping and 51 CHIVA)

Sex: 38 men and 62 women

Age (mean): 49 years (range 26-69)

Inclusion criteria: according to the guidelines of the Society of Angiology and Vascular Surgery (SEAVC) including the presence of symptomatic varicose veins with saphenous involvement or perforating veins (or both), or asymptomatic large varicose veins with a potential risk of complications (varicophlebitis or bleeding)

Exclusion criteria: people with alterations in the deep venous system, with a history of venous thrombosis, with previous treatment (surgery or sclerotherapy), morbidly obese people, aged ≥ 70 years

Interventions

1) CHIVA: according to the cartographic map, different strategies were applied: CHIVA 1 (superficial venous drainage system with a single surgical procedure), CHIVA 2 (required 2 possible surgical steps to ensure the drainage of the system) and CHIVA 1+2 (with a single surgical procedure, the superficial system is not drained and therefore represents a conservative but not hemodynamic treatment)

2) Vein stripping

Outcomes

Primary endpoint: rate of complications and, clinical and hemodynamic outcomes

Secondary outcomes: type of anesthesia, surgical time, level of activity after 1 week of the intervention, time off work and cosmetic results at 1 and 6 months and annually, number of reoperations performed during the follow-up

Assessment: the week after surgery when the stitches were removed; at the first, third and sixth postoperative months; and annually thereafter to complete 5 years of follow-up

Assessment of recurrences:

"Finally, a patient was considered cured when he was clinically asymptomatic or was better, he was pleased with the aesthetic results and the objective assessment of varicosities was not visible or they were of a diameter less than 5 mm." "Thus, patients not included in this characterization would be considered as disease recurrence"

Notes

Grants from Fundació August Pi i Sunyer (Hospital Universitari de Bellvitge) and SEACV (Sociedad Española de Angiología y Cirugía Vascular)

Sample size not stated

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "The patients were randomized with the software Excel of Window"

Comment: we assume that the generation of random sequence was performed by computer

Allocation concealment (selection bias)Low risk

Quote: "the patients were allocated by phone"

Comment: there was allocation concealment because the investigator did not know the random sequence

Blinding of participants and personnel (performance bias)
All outcomes (participants)
High riskThe participants knew the intervention to which they were assigned
Blinding of participants and personnel (performance bias)
All outcomes (personnel)
High riskThe personnel knew the intervention assigned to the participant
Blinding of outcome assessment (detection bias)
All outcomes
High riskThere was no blinding of outcome assessors
Incomplete outcome data (attrition bias)
All outcomes
Low riskThe losses were minimal at 4% at 5-year follow-up (2 participants in each group)
Selective reporting (reporting bias)Low riskThe results of all outcomes prespecified in the methods of the trial report were presented. The trial protocol was not requested from the authors

Pares 2010

Methods

Design: randomized controlled trial

Number of participating centers: 1

Setting: hospital

Country: Spain

Unit of randomization: participant

Unit of analysis: participant

Follow-up: immediately postoperatively and 3, 6, 12, 24, 36, 48, and 60 months after surgery

Participants

Number of participants: 501 (156 striping with clinical marking, 159 stripping with duplex marking, 160 CHIVA)

Sex: 147 men and 354 women

Age: 48-50 years (standard deviation 12)

Inclusion criteria: people diagnosed with varicose veins by a vascular surgeon in the outpatient clinic and according to the criteria of the CEAP classification of venous insufficiency

Exclusion criteria: people with congenital venous disease, varicose veins secondary to previous thrombosis, post-thrombotic side effects, sclerotherapy, recurrent varicose veins, associated systemic diseases or people who did not agree to participate in the study, who refused surgery, who could not participate in long-term monitoring or women who had been pregnant for less than 6 months

Interventions

1) Group CHIVA: disconnection of the point reflux and preservation of the superficial venous system drainage

Points of venous reflux were closed by ligation and division reflux of the saphenofemoral junction (preserving draining veins and tributaries), ligation and division of the saphenopopliteal union (preserving the Giacomini vein drainage) or subfascial closure of perforating veins, preservation of the incompetent segments of great saphenous vein or short saphenous vein (or both), removal of secondary reflux points originating the varicose vein, the preservation of re-entry points (perforating vein), and phlebectomy of collateral veins with improper drainage

Physical and Doppler ultrasound examination to identify incompetent segments. A map was produced and printed with venous images, points of reflux, the diameter of the saphenous vein and superficial and re-entry points. These documents were the baseline for comparison in follow-up

2) Stripping with clinic marking: remove the incompetent superficial venous system

Before surgery, the surgeon decided which segments were incompetent and to be removed. The decision was based on physical examination, identification of incompetent segments and points of re-entry. The surgical procedure consisted of the closing of the points of reflux, by ligation and division of the saphenofemoral junction, tributaries veins in the groin or ligation and division of the saphenopopliteal union or subfascial closure of perforating veins, and removal of all the great saphenous vein or superficial venous system (or both) or phlebectomy.

3) Stripping with duplex marking: remove the incompetent superficial venous system

Surgical strategy was based on the closing of the points of reflux by ligation and division of the saphenofemoral junction in the groin, or ligation of tributary veins and division of the union or saphenopopliteal subfascial closure, of perforating veins, removal of only the incompetent segment of great saphenous vein or the superficial venous system (or both), phlebectomy of varicose veins and closing points of re-entry

The physical examination and Doppler ultrasound were used to identify incompetent segments. Authors carried out a map of varicose veins and ultrasound images were stored. Points of reflux were marked, also the diameter of the great saphenous vein and minor saphenous vein and re-entry points. These documents were the baseline for comparison in follow-up

Postoperative management: pressure bandage from the groin to the foot for 48 hours, then elastic stockings for 4 weeks. Analgesic and antithrombotic prophylaxis treatment were common to all participants

Outcomes

Primary endpoint: recurrence rate of varicosity (using Hobbs' classification) (Hobbs 1974) (Table 2)

Secondary outcomes: ultrasonographic recurrence of varicose veins, descriptive baseline characteristics, type of anesthesia, days of convalescence, clinical cure, clinical improvement and complications (deep vein thrombosis, pulmonary thromboembolism, death, bruises, subcutaneous inguinal hemorrhage, neuralgia of the saphenous nerve, wound infection and phlebitis)

Postsurgical complications were evaluated at 8 days' postintervention

Clinical follow-up and duplex ultrasonography with venous mapping were at 3, 6, 12, 24, 36 48, and 60 months after surgery

Notes

Authors were contacted to obtain information on the randomization process

Funding: Institute of Health Carlos III, Ministry of Health (Spanish Ministry of Health) and Consumption, by 2 research grant FIS 94/5365 and FIS 97/0694 (Spain), and a research grant from the Non-Invasive Vascular Diagnosis Area of the Spanish Society for Angiology and Vascular Surgery and Endovascular (Spanish Society of Angiology and Vascular Surgery), 2003

The sample size was specified in the methods section

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskThe publication does not specify the method of generating the randomization sequence. We contacted the authors who explained that the method of sequence generation was centralized and independent of the clinicians: randomization generated by computer in blocks of 6
Allocation concealment (selection bias)Low riskThe publication does not specify the method of allocation concealment. We contacted the authors who explained that the allocation was centralized by telephone and independent of the clinicians
Blinding of participants and personnel (performance bias)
All outcomes (participants)
High risk

Quote: "This was a randomized, open-label controlled trial"

Comment: it was an open study

Blinding of participants and personnel (performance bias)
All outcomes (personnel)
High risk

Quote: "This was a randomized, open-label controlled trial"

Comment: it was an open study

Blinding of outcome assessment (detection bias)
All outcomes
High risk

Quote: "This was a randomized, open-label controlled trial"

Comment: it was an open study

Incomplete outcome data (attrition bias)
All outcomes
Low riskThe losses were minimal: 15 (3%) participants
Selective reporting (reporting bias)Low riskThe results of all outcomes prespecified in the methods of the trial report were presented. The trial protocol was not requested from the authors

Zamboni 2003

  1. a

    CHIVA: conservative hemodynamic correction of venous insufficiency; SF-36: Short Form-36.

Methods

Design: randomized controlled trial

Number of participant centers: 1

Setting: hospital

Country: Italy

Unit of randomization: participant

Unit of analysis: ulcer and participant

Follow-up: twice a year for 3 years

Participants

Number of participants: 45

Ulcers: 47 ulcers (21 people with 23 ulcers treated with CHIVA; 24 people with 24 ulcers treated with compression)
Sex: 18 men and 27 women
Age (mean): 63 years

Inclusion criteria: people with venous ulcer

Exclusion criteria: aged ≥ 80 years, inability to walk, ulcers < 2 cm2 or > 12 cm2, diabetes, peripheral arterial disease or an ankle brachial index < 0.9, secondary or congenital venous disease (history of deep venous thrombosis or ultrasound evidence of deep venous obstruction or reflux (or both), congenital angiodysplasia)

Interventions

1) CHIVA group: operations were performed under local anesthesia and Doppler ultrasound. Depending on the location of the re-entry of the perforator were 2 different minimally invasive techniques:
a) The opening was located on the main venous trunk (type I cases)
b) The opening was located in the venous branches (type III cases)

Cases of type I: the operation included high ligation of the venous saphenofemoral or popliteal union completed by ligation and division of the venous saphenous trunk and insufficient branches. The result was the creation of a drainage flow down into the venous saphenous trunk re-entering the deep circulation through perforators
Cases of type III: the operation involved ligation and disconnection of the venous saphenous trunk insufficient branches. The process could contain a second step consisting of high ligation
Participants began to walk 1 hour after the operation with the ulcer protected with a bandage and with half elastic compression at the ankle. Participants were discharged after 3 hours and were visited twice per week the first week and then every week until the ulcer healed

2) Compression group: treated with foam dressing, zinc oxide and an inelastic bandage applied from the foot to the knee. Antibiotics were used selectively according to sensitivities. The dressing was changed every 3-5 days the first month and then every 7 days until the ulcer was healed. Once ulcers healed, elastic stockings were prescribed. In the case of recurrence, the dressing protocol was repeated

Monitoring: participants in both groups were reviewed clinically, completed the questionnaire on quality of life (SF-36), and underwent a Doppler ultrasound and plethysmography twice a year for 3 years

OutcomesPrimary outcomes: healing rate, recurrence rate
Secondary outcomes: ulcerated area, quality of life (SF-36 questionnaire)
Notes

Study authors were contacted to obtain information on the randomization process
Sample size was calculated

Grant funding: "Venous Ulcers: TISSUE AND GROWTH FACTORS HAEMODYNAMICS of the Italian Ministry of the University and Scientific and Technological Research (MURST)"

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

We contacted the first study author by e-mail. His response was: "

The study was preceded by a computer-generated randomisation list, structured in balanced blocks of 4 patients and prepared by the local dept. of mathematics, of course blinded to the treating physicians. Once the patient was included in the study the physician called the secretary of the department, who communicated him/her the arm. I hope this clear"

Comment: the generation of random sequence was blinded

Allocation concealment (selection bias)Low risk

We contacted the first study author by e-mail. His response was: "

The study was preceded by a computer-generated randomisation list, structured in balanced blocks of 4 patients and prepared by the local dept. of mathematics, of course blinded to the treating physicians. Once the patient was included in the study the physician called the secretary of the department, who communicated him/her the arm"

Comment: there was allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes (participants)
High riskIt was an open study
Blinding of participants and personnel (performance bias)
All outcomes (personnel)
High riskIt was an open study
Blinding of outcome assessment (detection bias)
All outcomes
High riskIt was an open study
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo losses to follow-up (3 years)
Selective reporting (reporting bias)Unclear riskThe paper did not report the results of quality of life. It is not clear if data of recurrence were based in ultrasounds or clinical parameters. There were insufficient data about the time to heal the ulcer to include in the analysis of the review
Table 2. Hobbs' classification and scores
  1. See Hobbs 1974.

Class Clinical indication
Class A (score 1)No visible and palpable varicose veins
Class B (score 2)A few visible and palpable varicose veins with diameter < 5 mm
Class C (score 3)Remaining or newly formed varicose veins with diameter > 5 mm
Class D (score 4)Incompetent main trunks and perforator

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Maeso 2001Controlled trial, not randomized, case-review study
Solis 2009Prospective, controlled trial, not randomized
Zamboni 1995Prospective, controlled trial, not randomized
Zamboni 1996Prospective, non-controlled clinical trial
Zamboni 1998Prospective, controlled trial, not randomized

Ancillary