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Treatment for superficial thrombophlebitis of the leg

  1. Marcello Di Nisio1,2,*,
  2. Iris M Wichers3,
  3. Saskia Middeldorp2

Editorial Group: Cochrane Vascular Group

Published Online: 30 APR 2013

Assessed as up-to-date: 23 NOV 2012

DOI: 10.1002/14651858.CD004982.pub5


How to Cite

Di Nisio M, Wichers IM, Middeldorp S. Treatment for superficial thrombophlebitis of the leg. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD004982. DOI: 10.1002/14651858.CD004982.pub5.

Author Information

  1. 1

    University "G. D'Annunzio" of Chieti-Pescara, Department of Medical, Oral and Biotechnological Sciences, Chieti, Italy

  2. 2

    Academic Medical Center, Department of Vascular Medicine, Amsterdam, Netherlands

  3. 3

    Healthcare Center Borgerstraat, Amsterdam, Netherlands

*Marcello Di Nisio, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, via dei Vestini 31, Chieti, 66013, Italy. mdinisio@unich.it.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 30 APR 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Andreozzi 1996

MethodsMulticentre, open RCT


ParticipantsPatients (n = 56) with ST or varicophlebitis of the lower limbs; 19 males, 36 females; mean age range 48 to 52 years. The diagnosis of ST was objectively confirmed by Doppler compression ultrasonography. Not reported if the included patients were hospitalised and/or non-hospitalised


InterventionsDesmin (Dermatan sulphate) (100 mg bid sc)

Desmin (200 mg od im)

Desmin (100 mg od sc)

Study treatment was given for 30 days


OutcomesPain and functional inability; local oedema; palpable thrombophlebitic cord; fever; hyperemia and cutaneous hyperthermia; adverse events or adverse drug reactions


NotesFunding: Alfa Wassermann S.p.A (Bologna, Italy) supplied Desmin

Disclosure of potential conflicts of interest: two authors from Alfa Wassermann S.p.A., Bologna, Italy


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskOpen study "open and multicenter"

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe number of patients analysed unclear. One patient discontinued treatment and was excluded from the baseline descriptive table

Selective reporting (reporting bias)Low riskAll outcomes reported in the methods section were addressed in the results or discussion section.

Anonymous 1970

MethodsPlacebo-controlled, double-blind RCT


ParticipantsPatients (n = 56) with ST of the calf (68%), thigh (16%), both (16%). Not reported if included patients were hospitalised and/or non-hospitalised. Not reported if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsIndomethacin (50 mg 3 tid)

Placebo

Study treatment was given for 1 week


OutcomesErythema, spontaneous pain, tenderness, oedema


NotesEvery patient received tetracyclines (250 mg 4 times/day), paracetamol when required, warm socks (5 patients in the indomethacin group, 3 in the placebo)

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported. "..comparison between indomethacin and inactive placebo..the choice being determined by random selection"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blind study. "double-blind comparison", however, It is not reported who was blinded and how blinding was attempted

Incomplete outcome data (attrition bias)
All outcomes
High riskNot clear how many patients of those initially included had full assessment of the study endpoints. From Table I in Anonymous 1970 it is clear that at least for one of the outcomes not all patients were evaluated at the longest follow-up

Selective reporting (reporting bias)High riskNo data are provided for some of the outcomes. Side effects are reported in the Results section but not mentioned in the methods section.

Archer 1977

MethodsMulticentre, double-blind RCT


ParticipantsNon-hospitalised patients (n = 54) with ST; 18 males, 36 females; mean age 55 years. Not reported if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsOxyphenbutazone (Tandacote) (100 mg 4 times daily)

Placebo (4 times daily)

Study treatment was given for 7 days


OutcomesPain, erythema, tenderness, length of indurated vein


NotesParacetamol and firm bandaging allowed. Outcome tenderness assessed in 24 out of 26 patients in the oxyphenbutazone group

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported. "Oxyphenbutazone..and matching placebo were allocated at random"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo clear information provided about blinding: . "...none was a satisfactory double-blind controlled study...". "...it was felt that such a study should be undertaken..". It could be a double blinded study, however, blinding is not clearly mentioned in the methods, results or discussion sections. It is not reported who was blinded and how blinding was attempted

Incomplete outcome data (attrition bias)
All outcomes
High risk1 patient (from the placebo group) was excluded post-randomisation (2%). Unclear if all the remaining patients were analysed

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Belcaro 1989

MethodsOpen RCT


ParticipantsPatients (n = 83) with ST without DVT on duplex ultrasonography; 36 males, 45 females; mean age 38.9 years (range 27 - 46). Not reported if patients were hospitalised or non-hospitalised


InterventionsSuperficial thrombectomy plus ECB

Calcium heparin (0.5 mg bid sc) plus ECB

Venoruton (1000 mg tid) plus ECB

Venoruton (1000 mg tid) after superficial thrombectomy plus ECB

ECB alone

Non-surgical treatment was given for 8 weeks


OutcomesArea of maximum temperature; pain and tenderness (analogical score); DVT. Not specified if DVTs were symptomatic or asymptomatic


Notes6 of the 9 patients excluded post-randomisation underwent surgery of the superficial venous system. DVT was verified at 6 weeks by strain-gauge plethysmography

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available

Gianni Belcaro was erased from the UK medical register in June 2007 for "misconduct", which seems to have been that he included as co-authors on his papers people who were not involved in the research. The GMC report did not suggest that data were falsified http://webcache.gmc-uk.org/minutesfiles/3313.HTML.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported. "patients were randomized in 5 groups of treatment"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskNo information provided about blinding, but it is likely an open study

Incomplete outcome data (attrition bias)
All outcomes
High riskNine patients were excluded after inclusion in the study (10%): "6 patients underwent surgery of the superficial venous system and 3 failed to follow the prescribed treatments"

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Belcaro 1990

MethodsSingle-centre RCT


ParticipantsPatients (n = 40) with ST confirmed by colour duplex ultrasonography; 13 males, 27 females; age range 46 to 48 years. Not reported if patients were hospitalised or non-hospitalised. Angiodynography was used to exclude the presence of obstruction and DVT


InterventionsDefibrotide (first week 400 mg bid; second and third weeks 400 mg od)

Low-dose heparin (5000 IU bid sc) for 3 weeks


OutcomesArea of maximum temperature, analogue score (redness, local tenderness, inflammation)


NotesAll patients got compression bandages

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available

Gianni Belcaro was erased from the UK medical register in June 2007 for "misconduct", which seems to have been that he included as co-authors on his papers people who were not involved in the research. The GMC report did not suggest that data were falsified http://webcache.gmc-uk.org/minutesfiles/3313.HTML.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported: "Patients were randomized in two treatment groups"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskNo information provided about blinding, but it is likely an open study

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear if all included patients were evaluated for study outcomes

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Belcaro 1999

MethodsMulticentre, open RCT; 6-month follow-up


ParticipantsNon-hospitalised patients (n = 562) with ST, large varicose veins, and venous incompetence; 181 males, 263 females; mean age range across study groups 53 to 56 years. The diagnosis of ST was objectively confirmed by colour Doppler compression ultrasonography


InterventionsSurgery (ligation)

Surgery (complete stripping)

Low-dose sc heparin

LMWH

Coumadin


OutcomesDVT and extension of ST after treatment and after 3 and 6 months. Not specified if DVT and extension of ST were symptomatic or asymptomatic


NotesAll patients got compression bandages. The duration of the non-surgical treatments is unclear and the dose of heparin or coumadin was not specified

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available

Gianni Belcaro was erased from the UK medical register in June 2007 for "misconduct", which seems to have been that he included as co-authors on his papers people who were not involved in the research. The GMC report did not suggest that data were falsified http://webcache.gmc-uk.org/minutesfiles/3313.HTML.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskNo information provided about blinding, but it is likely an open study

Incomplete outcome data (attrition bias)
All outcomes
High risk118 patients lost to follow-up (21%)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Belcaro 2011

MethodsSingle-centre, randomised, placebo-controlled study


ParticipantsNon-hospitalised patients (n = 120) with ST of the legs within 72 hours prior to study inclusion. ST was confirmed by colour-Doppler ultrasonography. Mean age was 46.3 years (11.51), 26 males, 94 females


InterventionsHeparin-spray gel (Viatromb 2.400 IU/g): 4.122 IU sodium heparin applied as 3 times 3 spray puffs
Heparin-spray gel (Viatromb 2.400 IU/g): 5496 IU sodium heparin applied as 3 times 4 spray puffs

Heparin-spray gel (Viatromb 2.400 IU/g): 6879 IU sodium heparin applied as 3 times 5 spray puffs

Placebo applied as 3 times 5 puffs

Study medication was applied for 7 to 14 days


OutcomesPain reduction (VAS scale and VRS), erythema extension, thrombus size, oedema reduction, adverse events, investigator's and subject's assessment of efficacy


NotesFunding: The study was sponsored by CRO Opera S.r.L., Genoa, Italy.

Disclosure of potential conflicts of interest: the authors report to have no COI

Gianni Belcaro was erased from the UK medical register in June 2007 for "misconduct", which seems to have been that he included as co-authors on his papers people who were not involved in the research. The GMC report did not suggest that data were falsified http://webcache.gmc-uk.org/minutesfiles/3313.HTML.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated: "The treatments were allocated according to a randomization list (randomization by blocks)."
Block allocation sequences were created at random by using numbers generated by a computer program".

Allocation concealment (selection bias)Low riskComputer-generated randomisation sequence "Each subject enrolled into the study received the respective lowest randomization number available."

Blinding (performance bias and detection bias)
All outcomes
High riskSingle blind: "observer blinded design"

Incomplete outcome data (attrition bias)
All outcomes
High risk14 of 150 (11.7%) dropped out, 68.3% completed treatment on day 7, 11.7% on day 14, and 8.3% had a treatment failure

Selective reporting (reporting bias)High riskData are not reported for all pre-specified outcomes. The outcome DVT is mentioned in the methods but not reported in the results or discussion

Cosmi 2012

MethodsSTEFLUX: Multicentre, randomised, double-blinded, placebo-controlled study


ParticipantsConsecutive outpatients (n = 664) with at least a 4-cm long ST of long or short saphenous veins or their collaterals confirmed by CUS. ST of the long saphenous or short saphenous vein within 3 cm to, respectively, the sapheno-femoral or sapheno-popliteal junction were excluded. Median age was 69 yrs (20-94); males 37% (246/664)


InterventionsIntermediate dose LMWH (parnaparin 8500 IU od) for 10 days followed by placebo for 20 days

Intermediate dose LMWH (parnaparin 8500 IU od for 10 days followed by 6400 IU od for 20 days)

Prophylactic dose LMWH (parnaparin 4250 IU od) for 30 days


OutcomesEfficacy outcomes

Primary: composite of symptomatic and asymptomatic DVT, symptomatic PE and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days

Secondary: a) reduction in local symptoms during treatment, b) the combined efficacy end-point during a follow-up of 93 days after the start of treatment

Safety outcomes

Primary: major bleeding
Secondary: composite of minor bleeding, thrombocytopenia or any other adverse events (e.g. local allergic reactions)


NotesPatients were instructed to wear graduated elastic stockings (knee-high or at the thigh) with a compression of 20–40 mmHg at the ankle, unless contraindicated. Oral or topical NSAIDS were permitted for only 4 days after study inclusion. Only paracetamol naproxen or ibuprofen were allowed.

The study was prematurely interrupted according to predefined stopping rules.

Funding: the study was supported by the non-profit organisation Angioclot in the Department of Angiology and Blood Coagulation, S.Orsola Malpighi University Hospital through an unrestricted grant by Alfa Wassermann, Bologna, Italy which had no say in study design; analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Alfa Wassermann provided the study drug and placebo.

Disclosure of potential conflicts of interest: three authors including the lead author reported to have received consulting fees from Alfa Wasserman


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCentral computer-generated randomisation sequence: "The randomization sequence was computer generated centrally in blocks of six"

Allocation concealment (selection bias)Low riskCentral computer-generated randomisation sequence: "The randomization sequence was computer generated centrally in blocks of six and centers were provided with consecutively numbered boxes of identically appearing prefilled syringes."

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble blinded: "Consecutive outpatients were randomly assigned to receive in a double-blind fashion one of the following subcutaneous treatments" . "All primary and secondary outcomes were evaluated by a central adjudication committee, whose members were not involved in patient recruitment"

Incomplete outcome data (attrition bias)
All outcomes
High risk16 out 664 (2.4%) patients excluded from the analysis, 8 lost to follow-up

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

De Sanctis 2001

MethodsPlacebo-controlled RCT


ParticipantsPatients (n = 30) with ST confirmed by colour duplex ultrasonography and varicose veins; mean age 51 years; 17 males, 13 females. Not reported if patients were hospitalised and/or non-hospitalised


InterventionsEssaven gel (5 cm of gel)

Placebo (5 cm of gel)

Study treatment was given for 4 weeks


OutcomesAverage decrease in temperature; average symptomatic score (local pain, disability, swelling)


NotesAll patients received LMWH (Clexane 0.1ml/10kg of body weight od) for 4 weeks and elastic compression stockings

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported: "the randomization process was controlled by an external statistical controller according to GCP rules"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study: "Placebo comparable to Essaven gel was used", "operators were unaware of the contents of the tube"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Decousus 2010a

MethodsCALISTO: Multicentre, randomised, double-blind, placebo-controlled study, intention-to-treat analysis


ParticipantsHospitalised or non-hospitalised patients (n = 3002) 18 years of age or older, with acute, symptomatic lower limb superficial-vein thrombosis at least 5 cm long, as confirmed by standardised compression ultrasonography.

Mean age 57.1 ± 13.3 yrs fondaparinux and 56.9 ± 13.6 yrs placebo. 1084 Males, 1918 females


InterventionsFondaparinux (2.5 mg sc od)

Placebo

Study treatment was given for 45 days


OutcomesPrimary efficacy outcome:

Composite of death from any cause or symptomatic PE, symptomatic DVT, or symptomatic extension to the saphenofemoral junction or symptomatic recurrence of superficial-vein thrombosis at day 47

Secondary efficacy outcomes: the composite primary efficacy outcome up to day 77 and the following outcomes up to day 47 and 77: each component of the primary efficacy outcome, the composite of symptomatic PE or DVT, and surgery for ST

Primary safety outcome: major bleeding

Secondary safety outcomes: clinically relevant non-major, minor, total (any) bleeding, arterial thromboembolic events, adverse events


NotesIn the fondaparinux group, 83.0% of patients received graduated compression stockings, 41.5% topical NSAIDs, 3.9% topical anticoagulant drugs, 2.1% oral NSAIDs or COX-2 inhibitors, 1.1% oral or parenteral anticoagulant drugs, 21.4% aspirin or other antiplatelet agents. The corresponding values in the placebo group were similar (83.1%, 41.8%, 3.3%, 3.7%, 6.4%, and 22.6%) except for anticoagulant drugs and oral NSAIDs which were prescribed more frequently than in the fondaparinux group.

Funding: the study was funded by the GlaxoSmithKline which collected and analysed the data

Disclosure of potential conflicts of interest: all authors reported to have received grant support and supporting fees from GlaxoSmithKline


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer based: "computer-generated randomisation list"

Allocation concealment (selection bias)Low riskCentral allocation: "with the use of a central telephone system and a computer-generated randomization list, consecutive patients were randomly assigned.."

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study. "Fondaparinux and placebo were packaged in identical boxes containing visually identical, prefilled 0.5-ml single-dose syringes". "All symptomatic outcomes were reviewed by the central adjudication committee, whose members were unaware of the patients’ group assignments"."The database of adjudicated outcomes was managed by an independent central adjudication committee"

Incomplete outcome data (attrition bias)
All outcomes
Low riskEfficacy analyses performed on data from the intention-to-treat data. Safety analyses were performed on data from the as-treated population. Overall, 18 patients in the fondaparinux group (1.2%) and 22 in the placebo group (1.5%) did not have a primary efficacy assessment. Overall, 1.8% of the randomised patients did not complete follow-up

Safety analysis "1499 patients in the fondaparinux group (99.8%) and 1488 in placebo group (99.2%) were included in the safety analyses."

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Ferrari 1992

MethodsSingle centre, open RCT


ParticipantsPatients (n = 50) with acute ST; 22 males, 28 females; median age 52 years. Not reported if patients were hospitalised or non-hospitalised nor if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsNimesulide (100 mg bid)

Diclofenac sodium (50 mg bid)

Study treatment was given for 10 days


OutcomesSpontaneous pain, hyperaemia, oedema, local hyperaemia, fever, tolerability


NotesAll patients received prophylaxis with heparin calcium

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported: "randomly allocated to oral treatment"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote from the abstract: "Double-blind study". However, blinding is not mentioned in the methods, results or discussion sections. It is not reported who was blinded and how blinding was attempted

Incomplete outcome data (attrition bias)
All outcomes
High riskOverall, 3 patients were not analysed for efficacy outcomes (6%): 2 patients in the nimesulide group and 1 in the diclofenac

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Gorski 2005

MethodsMulticentre, open, RCT; 7 to 14 day follow-up


ParticipantsNon-hospitalised patients (n = 46) with symptomatic ST confirmed by duplex ultrasonography with first symptoms not earlier than 72 hours before inclusion; 15 males, 31 females; mean age 52.5 years


InterventionsTopical liposomal heparin spray gel (4 puffs of 458 IU tid)

LMWH (enoxaparin 40 mg sc od)

Study treatment was given for 7 or 14 days


OutcomesPrimary outcomes: DVT, pain scoring, erythema, safety, tolerance. Not specified if DVTs were symptomatic or asymptomatic

Secondary outcomes: patient and investigator assessment of efficacy of treatment


NotesParacetamol up to 1000 mg/day and compression therapy permitted and documented

Funding: the study was sponsored by CSC Pharmaceuticals Handelsges, Austria

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"patient randomization was performed according to a prespecified randomization list"

Allocation concealment (selection bias)Unclear risk"each patient...was allocated to a treatment group according to the next free number on the randomization list".

It is not reported if allocation was done centrally

Blinding (performance bias and detection bias)
All outcomes
High riskOpen study: "treatment were administered in a open way, there was no blinding"

Incomplete outcome data (attrition bias)
All outcomes
High risk4 patients lost to follow-up (10%)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Holzgreve 1989

MethodsRCT


ParticipantsPatients (n = 60) with ST of the legs; 17 males, 43 females; mean age 53,4 ±12 years. Not reported if patients were hospitalised or non-hospitalised nor if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsEtofenak gel

Diclofenac gel


OutcomesLength of superficial venous thrombosis (cm), pain, redness, palpable veins, oedema


NotesAll patients had compression therapy

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskSingle-blinded. The authors state it is a single-blinded study, and the patients received medication that was labelled as "trial medication". It is unclear from the paper whether the trial physician was blinded to the treatment, and since the outcome was symptom improvement, there is a high risk of detection bias by imperfect blinding.

Incomplete outcome data (attrition bias)
All outcomes
High risk20 patients lost to follow-up (33%)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Incandela 2001

MethodsMulticentre, placebo-controlled RCT


ParticipantsPatients (n = 30) with ST confirmed by colour duplex ultrasonography and varices; 14 males, 16 females; mean age 54 years. Not reported if patients were hospitalised or non-hospitalised


InterventionsEssaven gel (5 cm of gel)

Placebo (5 cm of gel)

Study treatment was given for 8 weeks


OutcomesAnalog clinical/symptomatic score including pain, tenderness, disability, local swelling, erythema, presence of thrombosis


NotesAll patients received LMWH (enoxaparin 0.1ml/10kg of body weight od) for the initial 4 weeks of the study and elastic compression stockings for the study period

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskUnclear method of random sequence generation: "randomisation process was controlled by an external statistical controller"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blinded. "Placebo comparable to Essaven gel was used", "operators were unaware of the contents of the tube

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear if all patients included were analysed

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Katzenschlager 2003

MethodsMulticentre, open RCT


ParticipantsNon-hospitalised patients (n = 42) with ST diagnosed by duplex ultrasonography with signs and symptoms lasting less than 72 hours; 11 males, 31 females; mean age 52 years


InterventionsTopical liposomal heparin spray gel (Lipohep 2400 IU/g, 4 spray puffs tid) plus compressive stockings

LMWH (enoxaparin 40 mg sc) plus compressive stockings

Study treatment was given for 7 to 14 days


OutcomesMedian pain (VAS scale), median area of erythema, thrombus size


NotesPatients received paracetamol (1000 mg/day) as pain rescue medication

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"The assignment of patients to treatment was done accordingly to a randomisation list using a validated system"

Allocation concealment (selection bias)Unclear risk"Each valid subject...was assigned to the next number on the randomization list". Unclear if allocation was done centrally

Blinding (performance bias and detection bias)
All outcomes
High riskOpen study: "treatments were administered in a open randomised way"

Incomplete outcome data (attrition bias)
All outcomes
High risk3 patients, all in the heparin spray gel group, lost to follow-up (7%)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Koshkin 2001

MethodsPlacebo-controlled, double-blinded RCT


ParticipantsPatients (n = 119) with acute ST confirmed by duplex ultrasonography; mean age 54.5 years. Not reported if patients were hospitalised and/or non-hospitalised patients


InterventionsSystemic enzyme therapy (Wobenzym) (10 tablets 3 tid)

Placebo

Study treatment was given for 16 days


OutcomesPositive changes for a combined outcome including pain, redness, and oedema


NotesFunding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blind study, however, it is not reported who was blinded and how blinding was obtained

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information provided. Unclear if all included patients were evaluated for study outcomes

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Kuhlwein 1985

MethodsMulticentre, placebo-controlled RCT


ParticipantsPatients (n = 76) with ST, diagnosed on signs and symptoms only by general practitioners or internists. Not reported if some patients were hospitalised. No data on sex or age were reported.


InterventionsVasotonin forte

Placebo

Study treatment was given for 3 weeks


OutcomesOverall score including pain, redness, swelling, movement improvement


NotesFunding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blind study. The authors state in the abstract that the study was double-blinded and placebo-controlled. However, no details regarding the study medication or placebo are given in the text.

Incomplete outcome data (attrition bias)
All outcomes
Low riskIt appears that after 3 weeks there were no losses to follow-up

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Lozano 2003

MethodsOpen RCT


ParticipantsPatients (n = 60) with saphenous proximal thrombophlebitis confirmed by Doppler ultrasonography; 22 males, 38 females; mean age 59 years. Not reported if patients were hospitalised or non-hospitalised


InterventionsLMWH (enoxaparin 1mg/kg bid for the first week, then 1 mg/kg for 3 weeks) on an outpatient basis

Saphenofemoral disconnection with a short hospital stay


OutcomesResolution of symptoms and signs, ST recurrence, VTE, complications from treatment, socioeconomic assessment. Not specified if VTE and ST recurrence were symptomatic or asymptomatic


NotesIn the immediate postoperative period, a compression bandages/elastic stocking was used and early walking recommended. Pain was controlled with oral acetaminophen (500 mg). Compressive bandage/elastic stockings were continued at home by all patients.

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskOpen study

Incomplete outcome data (attrition bias)
All outcomes
High risk3 patients, all in the saphenofemoral disconnection group, lost to follow-up (5%)

Selective reporting (reporting bias)High riskNo information provided on the resolution of signs and symptoms

Marchiori 2002

MethodsSingle-centre RCT


ParticipantsConsecutive patients (n = 60) with ST of the great saphenous vein confirmed by ultrasonography; 26 males, 34 females; mean age 62 years. Not reported if patients were hospitalised or non-hospitalised


InterventionsUFH (12500 IU sc for one week then 10000 IU)

UFH (5000 IU)

Study treatment was given for 4 weeks


OutcomesAsymptomatic and symptomatic recurrence and/or extension of ST and VTE after treatment and at 3 and 6 months

Safety outcomes: major bleeding, heparin-induced thrombocytopenia, overall mortality


NotesSystemic and/or local anti-inflammatory drugs were allowed

Funding: not reported

Disclosure of potential conflicts of interest: the authors report no COI


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-based: "List generated by a computer"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskThe ultrasound assessment was performed by blinded investigators. However, it is not reported if patients and investigators evaluating all other events were blinded to study treatment

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Marshall 2001

MethodsMulticentre, placebo-controlled RCT


ParticipantsPatients (n = 159) with acute ST of the leg, diagnosed on symptoms and signs only; 40 males, 116 females; mean age 53.8 years. Not reported if patients were hospitalised or non-hospitalised


InterventionsWobenzym (4 tablets tid)

Placebo

Study treatment was given for 12 to 16 days


OutcomesThe reduction of pain until day 7 which had to amount to at least 4 points on the Visual Rating Analogue Scale (VRAS) at baseline


NotesLMWH was allowed and administered to 4 patients. Paracetamol (maximal 2g/day) plus compression stockings were given to all patients. Nine patients had already been treated with other medications, not better specified, which were stopped before the administration of study treatment. Four patients had received LMWH before inclusion and continued LMWH throughout the study.

Funding: not stated

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-based. Patients assigned to treatment with a list generated by a computer

Allocation concealment (selection bias)Low riskPatients assigned to treatment with a list generated by a computer. Concealment of allocation was present since randomisation took place with a computer program called "Random V.5" by Firma Wiedey GmbH Konstanz.

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study. The study medication is described as "similarly looking study medication [placebo]",

Incomplete outcome data (attrition bias)
All outcomes
High risk1 withdrew consent post-randomisation; 10 patients lost to follow-up (6%)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Messa 1997

MethodsSingle-centre, open RCT


ParticipantsPatients (n = 30) with ST; 7 males, 23 females; age range 32 to 72 years. Not reported if patients were hospitalised or non-hospitalised nor if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsHeparansulphate (100 mg 3 tid orally)

Sulodexide (250 LSU bid, orally)

Study treatment was given for 2 weeks


OutcomesRedness of the skin, pain, itching, oedema, trophism


NotesFunding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients assigned to treatment with a random list

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskOpen study. "The study was performed in a open-label..design"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Nocker 1991

MethodsPlacebo-controlled RCT


ParticipantsPatients (n = 20) with unilateral ST of the legs diagnosed on symptoms and signs only; 8 males, 12 females; mean age 59.7 ± 7.1 years in the intervention group; 54.6 ± 5.6 years in placebo group. Not reported if patients were hospitalised or non-hospitalised


InterventionsDiclofenac gel (1 g diclofenac/100 g gel) applied three times a day

Placebo applied three times a day

Study treatment was given for 3 weeks


OutcomesEfficacy was measured by the volume change relative to baseline (difference between the affected and unaffected leg) and the reduction in pain described by a Visual Analogue Scale); tolerability


NotesHeparin gel was given to 10 patients, without randomisation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDouble-blind study. The authors state that the study was double-blinded and placebo-controlled. However, no details regarding the study medication or placebo are given in the main text

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Nusser 1991

Methods RCT


ParticipantsPatients (n = 60) with ST diagnosed on symptoms and signs only; 25 males, 34 females with mean age of 53 ± 13 and 53 ± 16 years, respectively. Not reported if patients were hospitalised or non-hospitalised


InterventionsOral acemetacin (60 mg tid)

Oral diclofenac (50 mg tid)

Study treatment was given until symptoms resolved for maximally 15 days


OutcomesArea of ST, pain, redness, palpable venous induration, oedema


NotesAll patients received compression stockings

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study. The study medication is described as "similarly looking study medication".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear if all included patients were evaluated for study outcomes

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Pinto 1992

MethodsMulticentre, placebo-controlled RCT


ParticipantsPatients (n = 68) with ST; mean age 42 years. Not reported if patients were hospitalised or non-hospitalised nor if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsTopical 5'-methylthioadenosine 0.5% (0.1 ml/cm skin tid)

Placebo

Study treatment was given for 1 week


OutcomesOedema, erythema, pain, functional impairment, subcutaneous induration, tolerability, VAS score


NotesNo compression therapy was allowed during the study.

Patients with ST represent a subgroup of a larger RCT which included also patients with chronic venous insufficiency or second degree haemorrhoids.

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study. "indistinguishable placebo"

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear if all included patients were evaluated for study outcomes

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Rathbun 2012

MethodsRandomised, controlled, double-blind, double-dummy trial


ParticipantsConsecutive inpatient and outpatients (n = 72) with ST of the lower (n = 57) or upper extremities confirmed by ultrasonography in the absence of a current intravenous catheter. ST involved the lower extremities in 27/37 of the patients in the dalteparin group and in 30/35 in the ibuprofen group. Mean age was 51 yrs (28 – 88) in dalteparin and 52 (19 – 85) in ibuprofen. 21 males, 51 females


InterventionsLMWH (dalteparin 200 IU/kg at presentation followed by a fixed dose of 10,000 units sc daily for additional 6 – 13 days) plus placebo given orally tid for 7 days

Ibuprofen 800 mg given orally three times daily for up to 14 days plus placebo injection od for 7 days

If symptoms of ST were not resolved at day 7–9, in the absence of thrombus extension, the patient received an additional 7 days of the blinded therapy. If symptoms of ST were resolved at day 7-9 in the absence of thrombus extension, study medication was stopped.
If at any time thrombus was found to extend either superficially or into the deep venous system, study treatment was discontinued and full therapeutic anticoagulation with iv heparin or low-molecular-weight heparin started


OutcomesEfficacy outcomes

Primary: incidence of thrombus extension or new symptomatic VTE during the 14-day and 3-month follow-up period

Secondary: reduction in pain, evaluated through the 11-point Box Pain scale, from baseline to day 7 and 14-16 day follow-up

Safety outcomes

Incidence of major and minor bleeding


NotesCompression stockings not routinely prescribed

Funding: grant from the National Center for Research Resources, National Institute of Health and Pfizer Inc. for provision of dalteparin, ibuprofen and nurse personnel salary support

Disclosure of potential conflicts of interest: the authors report no COI


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Balanced randomization blocks of four each consisting of equal numbers" for the 2 treatment groups

Allocation concealment (selection bias)Low risk"randomization..was performed by the investigational pharmacist within 24 h of presenting with a confirmed diagnosis.."

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blinded. "The patient, research assistant and principal investigator were blinded to the treatment group"

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear if all included patients were evaluated for study outcomes

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Stenox Group 2003

MethodsSTENOX: Multicentre, placebo-controlled RCT with a 3-month follow-up, intention-to-treat analysis


ParticipantsHospitalised or non-hospitalised patients (n = 427) with ST of at least 5 cm on ultrasonography examination; 156 males, 271 females; mean age 62 years


InterventionsLMWH (enoxaparin 40 mg sc od)

LMWH (enoxaparin 1.5 mg/kg sc od)

Oral tenoxicam (20 mg od)

Placebo

Study treatment was given for 8 to 12 days


OutcomesPrimary efficacy outcome: symptomatic PE and symptomatic and asymptomatic DVT at 12 days

Secondary efficacy outcomes: Symptomatic and asymptomatic recurrence and/or extension of ST at 12 days and 3 months; symptomatic PE and symptomatic and asymptomatic DVT at 12 days and 3 months (97 days)

Safety outcomes: death, major and minor bleeding, thrombocytopenia, and any other adverse event


NotesAll patients used elastic bandages or support stockings from day 1 of therapy and continued for at least 15 days. Patients requiring anticoagulant therapy, ligation of the saphenofemoral junction or thrombectomy, anticoagulants or NSAIDs for more than 48 hours were excluded from the study.

The study was prematurely interrupted due to slow recruitment rate.

Funding: Laboratoires Aventis, Paris and Association Francaise de Formation Continue en Angiologie, Paris

Disclosure of potential conflicts of interest: the authors report no financial interests


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskUnclear method of sequence generation: "patients were centrally randomly assigned to receive.."

Allocation concealment (selection bias)Low riskCentral allocation

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study: "study medications were packaged in boxes of identical appearance.", "all boxes had visually identical contents". "outcomes were reviewed blindly by an independent critical event committee"

Incomplete outcome data (attrition bias)
All outcomes
High risk9/436 patients lost to follow-up (2%)

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Titon 1994

MethodsMulticentre, open RCT


ParticipantsNon-hospitalised patients (n = 117) with ST confirmed by ultrasonography; 25 males, 92 females; age range 54 to 64 years. Mean ages vary between groups, particularly for the few men in the dose adjusted group of nadroparin who were much younger than the men in the other two groups.


InterventionsNaproxene (oral 500 mg od)

LMWH (nadroparin 0.6 ml /6150 anti-Xa IU od)

LMWH (nadroparin 61.5 anti-Xa IU/kg sc od)

Study treatment was given for 6 days


OutcomesPrimary efficacy: Recurrence and/or extension of ST, VTE after treatment (day 7) and after 8 weeks

Secondary efficacy outcomes: symptoms (pain and functional disability) and signs (erithema, oedema)

Safety outcomes: major and minor bleeding


NotesAll patients received elastic stockings for the first 7 days.

Funding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of random sequence generation not reported

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskOpen study. "open trial".

Incomplete outcome data (attrition bias)
All outcomes
High riskAt day 7, no patients were lost to follow up. Four (3.4%) patients were not evaluated by ultrasonography. At 8 weeks, 8 (6.8%) patients were lost to follow-up and 25 (21%) patients were not evaluated by ultrasonography

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Uncu 2009

MethodsOpen RCT


ParticipantsPatients (n = 50) with ST of the greater saphenous vein of at least 5 cm in length on duplex ultrasonography. Not reported if patients were hospitalised or non-hospitalised. Mean age: 48.6 (25 - 90) years in Ca-nadroparin and 44.9 (28-85) years in Ca-nadroparin and acemetacin. 27 males, 23 females


InterventionsLMWH (Ca-nadroparin 190 IU Axa/Kg od)

LMWH (Ca-nadroparin 190 IU Axa/Kg od) + acemetacin (60 mg oral bid)

Study treatment was given for 10 days


OutcomesPrimary outcomes

Spontaneous pain, erythema, local tenderness and palpable cord


NotesFunding: not reported

Disclosure of potential conflicts of interest: not reported, no COI forms available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskAlternation: "consecutive alternating method"

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
High riskNo information provided about blinding, but it is likely an open study

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe authors do not report they performed an ITT and it is not clear whether the study outcomes were evaluated in all included patients

Selective reporting (reporting bias)High riskAll pre-specified outcomes are reported. The outcomes symptomatic DVT, PE, ST extension, bleeding, death, and AE were reported in the results but not mentioned in the methods

Vesalio Group 2005

MethodsVESALIO: Multicentre, double-blind, double-dummy RCT, intention-to-treat analysis


ParticipantsHospitalised or non-hospitalised patients (n = 164) with ST of the great saphenous vein with the thrombosis extending up to 3 cm from the saphenus-femoral junction; 60 males, 104 females; mean age 63 years. The diagnosis of ST was objectively confirmed by compression ultrasonography


InterventionsWeight adjusted LMWH (nadroparin full dose for 10 days followed by half dose for 20 additional days)

Fixed-dose LMWH (nadroparin 2850 anti-Xa IU)

Study treatment was given for 30 days


OutcomesPrimary efficacy outcome: asymptomatic and symptomatic extension of the ST, and/or VTE in a 3-month follow-up period.

Secondary efficacy outcomes: clinical signs and symptoms

Primary safety outcomes: major bleeding, heparin-induced thrombocytopenia


NotesNo aspirin use or NSAIDs use throughout the study

Study prematurely interrupted due to the slow recruitment rate

Funding: grant from Sanofi-Synthelabo, Sanofi Aventis Group, Milano and GlaxoSmithKline, Verona

Disclosure of potential conflicts of interest: the authors declared no COI


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer based: "each patient was assigned a unique sequential subject number, generated by a computer"

Allocation concealment (selection bias)Unclear riskSealed envelopes, not clear if opaque. "each center received a initial fixed amount of randomization numbers and corresponding sealed envelopes

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind study. "placebo identical in appearance to nadroparin". "all suspected outcome events were reviewed and classified by a Central Adjuducation Committee whose members were unaware of treatment assignment"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)Low riskAll pre-specified outcomes are reported

Winter 1986

MethodsMulticentre, randomised trial


ParticipantsPatients with ST (n = 100). Not reported if patients were hospitalised or non-hospitalised nor if the diagnosis of ST was objectively confirmed by ultrasonography


InterventionsDiclofenac emulgel

Heparin gel

Study treatment was given 14 days


OutcomesPain (spontaneous and after pressure)

Redness

Palpable cord


NotesThis study is only reported as an abstract for a scientific meeting. No full paper available.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation list

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo information on study medication or outcome assessment is provided

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThe authors do not report whether they performed an ITT analysis

Selective reporting (reporting bias)Unclear riskOutcomes were not specified, only a general outcome of "efficacy" was reported

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Agus 1993Not possible to extract outcomes data separately for the two study-treatment groups.

Allegra 1981Mixed population. It was not possible to extract data separately for the ST.

Annoni 1991Mixed population. It was not possible to extract data separately for ST.

Argenteri 1983Mixed population including patients with deep venous thrombosis. It was not possible to extract data separately for ST.

Bagliani 1983Mixed population including also patients with DVT. It was not possible to extract data separately for ST.

Becherucci 2000Mixed population including patients with acute ST of the upper limb. It was not possible to extract data separately for ST of the lower limbs.

Bergqvist 1990Mixed population including patients with acute ST of the upper limb. It was not possible to extract data separately for ST of the lower limbs.

Bernicot 1980Patients without a diagnosis of ST of the legs.

Bracale 1996Mixed population including also patients with DVT. It is not possible to extract data separately for the ST.

Bruni 1979Mixed population including also patients with acute ST of the upper limb. It is not possible to extract data separately for the ST of the lower limbs.

Della Marchina 1989Mixed population including also patients with DVT and post-phlebitic syndrome. It is not possible to extract data separately for the ST.

Di Perri 1986Patients with DVT.

Gandhi 1984Patients without a diagnosis of ST of the legs.

Giorgetti 1990Single blind study of patients with varicophlebitis who received either Seaprose S or placebo. It is unclear whether the study was randomised or not.

Gouping 2003Patients with post-infusion ST of the arm.

Ibanez-Bermudez 1996The evaluated outcomes are not among those evaluated in the present review.

Luttichau 1989Mixed population. It was not possible to extract data separately for ST.

Mari 1982Mixed population including patients with acute ST of the upper limb. It was not possible to extract data separately for ST of the lower limbs.

Marsala 1985Mixed population. It was not possible to extract data separately for ST.

Mauro 1992Mixed population including patients with DVT. It was not possible to extract data separately for ST.

Mehta 1975Patients with ST of the arm.

Paciaroni 1982Mixed population including patients with chronic venous insufficiency. It is not possible to extract data separately for ST.

Porters 1981Mixed population including patients with acute ST of the upper limb. It was not possible to extract data separately for ST of the lower limbs.

Pozza 1980Mixed population including patients with acute ST of the upper limb. It was not possible to extract data separately for ST of the lower limbs.

Rea 1981Patients with DVT.

Resta 1967Patients without a diagnosis of ST of the legs.

Rozsos 1994Patients with ST of the arm.

Seccia 1989Mixed population including patients with acute ST of the upper limb. It was not possible to extract data separately for the ST of the lower limbs.

Seghezzi 1972Mixed population including patients with DVT and recurrent post-phlebitic syndromes. It was not possible to extract data separately for ST of the lower limbs.

Seligman 1969Mixed population including patients with DVT. It was not possible to extract data separately for ST.

Stolle 1986Patients with ST of the arm.

Tomamichel 1983Mixed population including patients with DVT. It was not possible to extract data separately for ST.

van Cauwenberge 1972Patients without a diagnosis of ST of the legs.

van der Knaap 1988Patients with ST of the arm.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Bijuan 2003

MethodsRandomised study

ParticipantsPatients (n = 64) with phlebitis but unclear if ST of the legs or upper extremities

InterventionsAloe pigmentum

Wet packing with routine 50% magnesium sulphate

OutcomesTo investigate the clinical effects of aloe pigmentum on phlebitis

Colour Doppler was used to detect and compare inner diameter of blood vessels before and after treatment in the two groups

Notes

 
Characteristics of ongoing studies [ordered by study ID]
Rabe 2009

Trial name or titleDAPS-dalteparin in patients with superficial leg vein phlebitis in addition to compression treatment - a placebo-controlled phase III study

MethodsRandomised, double-blind, multicentre, phase III trial

ParticipantsPatients (n = 276) with superficial leg vein phlebitis

InterventionsCompression stockings (30 mmHg) for 3 months and either dalteparin 10 000 IU (group A) or placebo (group B) for 14 days.

OutcomesPrimary end point: progression of the thrombotic process during the treatment period as confirmed by ultrasound. Sonographic assessment was planned in all patients on days 1, 7, 14, and 90.

Secondary end points: pain assessment by VAS and calculation of symptom scores (tension, heaviness, swelling).

Starting dateNot reported

Contact informationRabe E

Notes

 
Comparison 1. Fondaparinux versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pulmonary embolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Deep vein thrombosis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Deep vein thrombosis and pulmonary embolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Extension of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Mortality1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 Clinically relevant non-major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Minor bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 10 Arterial thromboembolic complication1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 11 Any adverse event1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 12 Non-fatal serious adverse event1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 2. Prophylactic LMWH versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism 3-month follow up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Heparin-induced thrombocytopenia1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 3. Therapeutic LMWH versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism 3-month follow up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Heparin-induced thrombocytopenia1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 4. Thirty-day prophylactic LMWH versus 30-day intermediate LMWH

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Symptomatic DVT end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Symptomatic DVT 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Extension of ST 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Recurrence of ST 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 5. Thirty-day prophylactic LMWH versus 10-day intermediate LMWH

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Symptomatic DVT end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Symptomatic DVT 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Extension of ST 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Recurrence of ST 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 6. Thirty-day intermediate LMWH versus 10-day intermediate LMWH

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Symptomatic DVT end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Symptomatic DVT 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Extension of ST 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Recurrence of ST 3-month follow-up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 7. Fixed-dose LMWH versus weight-adjusted LMWH

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 ST or venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism2238Risk Ratio (M-H, Fixed, 95% CI)0.51 [0.10, 2.72]

 3 Superficial thrombophlebitis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Swelling disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Tenderness disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Pain disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 Pitting oedema disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 Collateral veins disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Redness disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 10 Palpable cord disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 11 Major bleeding2238Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 12 Heparin-induced thrombocytopenia2238Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.07, 16.11]

 
Comparison 8. Therapeutic LMWH versus saphenofemoral disconnection

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Complications1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 9. Fixed-dose LMWH versus NSAIDs

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism2278Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.24, 3.63]

 2 Extension and/or recurrence of ST3331Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.58, 1.78]

 3 Major bleeding3335Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Heparin-induced thrombocytopenia2278Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 10. Weight-adjusted LMWH versus NSAIDs

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Heparin-induced thrombocytopenia1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 11. Prophylactic LMWH versus NSAIDs

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism end-of-treatment1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Venous thromboembolism 3-month follow up1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Extension and/or recurrence of ST1209Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.50, 1.84]

 4 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Heparin-induced thrombocytopenia1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 12. LMWH versus LMWH + acemetacin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pulmonary embolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Deep vein thrombosis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Extension of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Pain reduction1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 Hyperaemia reduction1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 6 Tenderness reduction1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 7 Palpable cord reduction1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 8 Mortality1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 10 Minor bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 11 Adverse event1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 13. Prophylactic LMWH + elastic compression stockings (ECS) versus elastic stockings alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 14. LMWH versus heparin spray gel

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Deep-venous thrombosis283Risk Ratio (M-H, Fixed, 95% CI)0.30 [0.03, 2.70]

 2 Patients with thrombus at 21 days1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Allergic reaction or elevated sedimentation rate1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 15. High-dose UFH versus low-dose UFH

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 ST recurrence or extension1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Heparin-induced thrombocytopenia1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 16. Calcium heparin + elastic compression bandage versus elastic compression bandage alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Deep venous thrombosis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 17. Heparin sc versus defibrotide

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Decrease in the analogue score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 2 Treatment side effects1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 18. NSAIDs versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Major bleeding1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Heparin-induced thrombocytopenia1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 19. Indomethacin versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Side effects1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 20. Nimesulide versus diclofenac sodium

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Gastric pain1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 21. Essaven gel versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Intolerance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 22. Thrombectomy + venoruton + elastic compression bandage versus elastic compression bandage alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Deep venous thrombosis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 23. Thrombectomy + elastic compression bandage versus elastic compression bandage alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Deep venous thrombosis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 24. Ligation + elastic compression stockings versus elastic compression stockings alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 25. Prophylactic UFH + elastic compression stockings versus elastic compression stockings alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 26. Oral vasotonin versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Cured or substantially better1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Poor tolerability1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 27. Elastic compression bandage + venoruton versus elastic compression bandage alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Deep venous thrombosis1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 28. Oral heparan sulphate versus oral sulodexide

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Redness disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Pain disappearance1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Disappearance of itching1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Oedema improvement1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Trophism improvement1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 29. Oxyphenbutazone versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Tenderness improvement1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 30. VKA + elastic compression stockings versus elastic compression stockings alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 31. Stripping + elastic compression stockings versus elastic compression stockings alone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Venous thromboembolism1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Extension and/or recurrence of ST1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 32. Enzyme therapy versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Pain reduction1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 2 Responders1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 33. Desmin im 200 versus desmin 100

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Adverse drug reactions1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 34. Desmin sc 2 x 100 versus desmin 100

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Adverse drug reactions1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected