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Meta-Analysis
. 2018 Feb 25;2(2):CD004982.
doi: 10.1002/14651858.CD004982.pub6.

Treatment for superficial thrombophlebitis of the leg

Marcello Di Nisio  1 , Iris M Wichers, Saskia Middeldorp
Affiliations
Meta-Analysis

Treatment for superficial thrombophlebitis of the leg

Marcello Di Nisio et al. Cochrane Database Syst Rev. .

Abstract

Background: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007.

Objectives: To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications.

Search methods: For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register (March 2017), CENTRAL (2017, Issue 2), and trials registries (March 2017). We handsearched the reference lists of relevant papers and conference proceedings.

Selection criteria: Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the legs that included people with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in a superficial vein.

Data collection and analysis: Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. We assessed the quality of the evidence using the GRADE approach.

Main results: We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects.

Authors' conclusions: Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

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Conflict of interest statement

MDN: Dr Di Nisio reported participation to Advisory Boards for Daiichi‐Sankyo and Pfizer, and receiving consultancy fees from Daiichi‐Sankyo and Bayer Health Care. IW: none known. SM: Dr Middeldorp was a member of the Steering Committee of the CALISTO study, which was funded by GlaxoSmithKline (GSK) and which investigated the efficacy and safety of fondaparinux for superficial thrombophlebitis; funds were paid to Dr Middeldorp's institution. Dr Middeldorp's institution had also received funding from several pharmaceutical companies, including GSK, BMS, Bayer, Boehringer Ingelheim, Sanofi, and Pfizer to support some of her other educational and research activities. The first version of this review was written before the CALISTO study was designed.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 1 Pulmonary embolism.
1.2
1.2. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 2 Deep vein thrombosis.
1.3
1.3. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 3 Deep vein thrombosis or pulmonary embolism.
1.4
1.4. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 4 Extension of superficial thrombophlebitis.
1.5
1.5. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 5 Recurrence of superficial thrombophlebitis.
1.6
1.6. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 6 Mortality.
1.7
1.7. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 7 Major bleeding.
1.8
1.8. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 8 Clinically relevant non‐major bleeding.
1.9
1.9. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 9 Minor bleeding.
1.10
1.10. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 10 Arterial thromboembolic complication.
1.11
1.11. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 11 Adverse effects of treatment.
1.12
1.12. Analysis
Comparison 1 Fondaparinux versus placebo, Outcome 12 Non‐fatal serious adverse event.
2.1
2.1. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 1 Pulmonary embolism.
2.2
2.2. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 2 Deep vein thrombosis.
2.3
2.3. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 3 Deep vein thrombosis or pulmonary embolism.
2.4
2.4. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 4 Extension of superficial thrombophlebitis.
2.5
2.5. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 5 Recurrence of superficial thrombophlebitis.
2.6
2.6. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 6 Mortality.
2.7
2.7. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 7 Major bleeding.
2.8
2.8. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 8 Clinically relevant non‐major bleeding.
2.9
2.9. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 9 Minor bleeding.
2.10
2.10. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 10 Serious adverse events.
2.11
2.11. Analysis
Comparison 2 Fondaparinux versus rivaroxaban, Outcome 11 Adverse effects of treatment.
3.1
3.1. Analysis
Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 1 Venous thromboembolism end‐of‐treatment.
3.2
3.2. Analysis
Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 2 Venous thromboembolism 3‐month follow‐up.
3.3
3.3. Analysis
Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 3 Extension or recurrence (or both) of superficial thrombophlebitis.
3.4
3.4. Analysis
Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 4 Major bleeding.
3.5
3.5. Analysis
Comparison 3 Prophylactic low molecular weight heparin (LMWH) versus placebo, Outcome 5 Heparin‐induced thrombocytopenia.
4.1
4.1. Analysis
Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 1 Venous thromboembolism end‐of‐treatment.
4.2
4.2. Analysis
Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 2 Venous thromboembolism 3‐month follow‐up.
4.3
4.3. Analysis
Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 3 Extension or recurrence (or both) of superficial thrombophlebitis.
4.4
4.4. Analysis
Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 4 Major bleeding.
4.5
4.5. Analysis
Comparison 4 Therapeutic low molecular weight heparin (LMWH) versus placebo, Outcome 5 Heparin‐induced thrombocytopenia.
5.1
5.1. Analysis
Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 1 Venous thromboembolism end‐of‐treatment.
5.2
5.2. Analysis
Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 2 Venous thromboembolism 3‐month follow‐up.
5.3
5.3. Analysis
Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 3 Symptomatic deep vein thrombosis end‐of‐treatment.
5.4
5.4. Analysis
Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 4 Symptomatic deep vein thrombosis 3‐month follow‐up.
5.5
5.5. Analysis
Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 5 Extension of superficial thrombophlebitis 3‐month follow‐up.
5.6
5.6. Analysis
Comparison 5 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 30‐day intermediate LMWH, Outcome 6 Recurrence of superficial thrombophlebitis 3‐month follow‐up.
6.1
6.1. Analysis
Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 1 Venous thromboembolism end‐of‐treatment.
6.2
6.2. Analysis
Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 2 Venous thromboembolism 3‐month follow‐up.
6.3
6.3. Analysis
Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 3 Symptomatic deep vein thrombosis end‐of‐treatment.
6.4
6.4. Analysis
Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 4 Symptomatic deep vein thrombosis 3‐month follow‐up.
6.5
6.5. Analysis
Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 5 Extension of superficial thrombophlebitis 3‐month follow‐up.
6.6
6.6. Analysis
Comparison 6 Thirty‐day prophylactic low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 6 Recurrence of superficial thrombophlebitis 3‐month follow‐up.
7.1
7.1. Analysis
Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 1 Venous thromboembolism end‐of‐treatment.
7.2
7.2. Analysis
Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 2 Venous thromboembolism 3‐month follow‐up.
7.3
7.3. Analysis
Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 3 Symptomatic deep vein thrombosis end‐of‐treatment.
7.4
7.4. Analysis
Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 4 Symptomatic deep vein thrombosis 3‐month follow‐up.
7.5
7.5. Analysis
Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 5 Extension of superficial thrombophlebitis 3‐month follow‐up.
7.6
7.6. Analysis
Comparison 7 Thirty‐day intermediate low molecular weight heparin (LMWH) versus 10‐day intermediate LMWH, Outcome 6 Recurrence of superficial thrombophlebitis 3‐month follow‐up.
8.1
8.1. Analysis
Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 1 Symptomatic venous thromboembolism.
8.2
8.2. Analysis
Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 2 Symptomatic pulmonary embolism.
8.3
8.3. Analysis
Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 3 Superficial thrombophlebitis progression into deep vein thrombosis.
8.4
8.4. Analysis
Comparison 8 Six‐week prophylactic low molecular weight heparin (LMWH) versus six‐week intermediate LMWH, Outcome 4 Major bleeding.
9.1
9.1. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 1 Superficial thrombophlebitis or venous thromboembolism.
9.2
9.2. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 2 Venous thromboembolism.
9.3
9.3. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 3 Superficial thrombophlebitis.
9.4
9.4. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 4 Swelling disappearance.
9.5
9.5. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 5 Tenderness disappearance.
9.6
9.6. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 6 Pain disappearance.
9.7
9.7. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 7 Pitting oedema disappearance.
9.8
9.8. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 8 Collateral veins disappearance.
9.9
9.9. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 9 Redness disappearance.
9.10
9.10. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 10 Palpable cord disappearance.
9.11
9.11. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 11 Major bleeding.
9.12
9.12. Analysis
Comparison 9 Fixed‐dose low molecular weight heparin (LMWH) versus weight‐adjusted LMWH, Outcome 12 Heparin‐induced thrombocytopenia.
10.1
10.1. Analysis
Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 1 Venous thromboembolism.
10.2
10.2. Analysis
Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
10.3
10.3. Analysis
Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 3 Major bleeding.
10.4
10.4. Analysis
Comparison 10 Therapeutic low molecular weight heparin (LMWH) versus saphenofemoral disconnection, Outcome 4 Complications.
11.1
11.1. Analysis
Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Venous thromboembolism.
11.2
11.2. Analysis
Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
11.3
11.3. Analysis
Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Major bleeding.
11.4
11.4. Analysis
Comparison 11 Fixed‐dose low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 Heparin‐induced thrombocytopenia.
12.1
12.1. Analysis
Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Venous thromboembolism.
12.2
12.2. Analysis
Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
12.3
12.3. Analysis
Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Major bleeding.
12.4
12.4. Analysis
Comparison 12 Weight‐adjusted low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 Heparin‐induced thrombocytopenia.
13.1
13.1. Analysis
Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 1 Venous thromboembolism end‐of‐treatment.
13.2
13.2. Analysis
Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 2 Venous thromboembolism 3‐month follow‐up.
13.3
13.3. Analysis
Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 3 Extension or recurrence (or both) of superficial thrombophlebitis.
13.4
13.4. Analysis
Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 4 Major bleeding.
13.5
13.5. Analysis
Comparison 13 Prophylactic low molecular weight heparin (LMWH) versus non‐steroidal anti‐inflammatory drugs (NSAIDs), Outcome 5 Heparin‐induced thrombocytopenia.
14.1
14.1. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 1 Pulmonary embolism.
14.2
14.2. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 2 Deep vein thrombosis.
14.3
14.3. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 3 Extension of superficial thrombophlebitis.
14.4
14.4. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 4 Pain reduction.
14.5
14.5. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 5 Hyperaemia reduction.
14.6
14.6. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 6 Tenderness reduction.
14.7
14.7. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 7 Palpable cord reduction.
14.8
14.8. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 8 Mortality.
14.9
14.9. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 9 Major bleeding.
14.10
14.10. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 10 Minor bleeding.
14.11
14.11. Analysis
Comparison 14 Low molecular weight heparin (LMWH) versus LMWH plus acemetacin, Outcome 11 Adverse events.
15.1
15.1. Analysis
Comparison 15 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.
15.2
15.2. Analysis
Comparison 15 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
16.1
16.1. Analysis
Comparison 16 Low molecular weight heparin (LMWH) versus heparin spray gel, Outcome 1 Deep vein thrombosis.
16.2
16.2. Analysis
Comparison 16 Low molecular weight heparin (LMWH) versus heparin spray gel, Outcome 2 Participants with thrombus at 21 days.
16.3
16.3. Analysis
Comparison 16 Low molecular weight heparin (LMWH) versus heparin spray gel, Outcome 3 Allergic reaction or elevated sedimentation rate.
17.1
17.1. Analysis
Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 1 Incidence of venous thromboembolism.
17.2
17.2. Analysis
Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
17.3
17.3. Analysis
Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 3 Major bleeding.
17.4
17.4. Analysis
Comparison 17 High‐dose unfractionated heparin (UFH) versus low‐dose UFH, Outcome 4 Heparin‐induced thrombocytopenia.
18.1
18.1. Analysis
Comparison 18 Heparin calcium plus elastic compression bandage (ECB) versus ECB alone, Outcome 1 Deep vein thrombosis.
19.1
19.1. Analysis
Comparison 19 Heparin subcutaneous (sc) versus defibrotide, Outcome 1 Decrease in the analogue score.
19.2
19.2. Analysis
Comparison 19 Heparin subcutaneous (sc) versus defibrotide, Outcome 2 Adverse effects of treatment.
20.1
20.1. Analysis
Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 1 Venous thromboembolism.
20.2
20.2. Analysis
Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
20.3
20.3. Analysis
Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 3 Major bleeding.
20.4
20.4. Analysis
Comparison 20 Non‐steroidal anti‐inflammatory drugs (NSAIDs) versus placebo, Outcome 4 Heparin‐induced thrombocytopenia.
21.1
21.1. Analysis
Comparison 21 Indomethacin versus placebo, Outcome 1 Adverse effects.
22.1
22.1. Analysis
Comparison 22 Nimesulide versus diclofenac sodium, Outcome 1 Gastric pain.
23.1
23.1. Analysis
Comparison 23 Essaven gel versus placebo, Outcome 1 Intolerance.
24.1
24.1. Analysis
Comparison 24 Thrombectomy plus venoruton plus elastic compression bandage (ECB) versus ECB alone, Outcome 1 Deep vein thrombosis.
25.1
25.1. Analysis
Comparison 25 Thrombectomy plus elastic compression bandage (ECB) versus ECB alone, Outcome 1 Deep vein thrombosis.
26.1
26.1. Analysis
Comparison 26 Ligation plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.
26.2
26.2. Analysis
Comparison 26 Ligation plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
27.1
27.1. Analysis
Comparison 27 Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.
27.2
27.2. Analysis
Comparison 27 Prophylactic unfractionated heparin (UFH) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
28.1
28.1. Analysis
Comparison 28 Oral vasotonin versus placebo, Outcome 1 Cured or substantially better.
28.2
28.2. Analysis
Comparison 28 Oral vasotonin versus placebo, Outcome 2 Poor tolerability.
29.1
29.1. Analysis
Comparison 29 Elastic compression bandage (ECB) plus venoruton versus ECB alone, Outcome 1 Deep vein thrombosis.
30.1
30.1. Analysis
Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 1 Redness disappearance.
30.2
30.2. Analysis
Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 2 Pain disappearance.
30.3
30.3. Analysis
Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 3 Disappearance of itching.
30.4
30.4. Analysis
Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 4 Oedema improvement.
30.5
30.5. Analysis
Comparison 30 Oral heparansulphate versus oral sulodexide, Outcome 5 Trophism improvement.
31.1
31.1. Analysis
Comparison 31 Oxyphenbutazone versus placebo, Outcome 1 Tenderness improvement.
32.1
32.1. Analysis
Comparison 32 Vitamin K antagonist (VKA) plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.
32.2
32.2. Analysis
Comparison 32 Vitamin K antagonist (VKA) plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
33.1
33.1. Analysis
Comparison 33 Stripping plus elastic compression stockings (ECS) versus ECS alone, Outcome 1 Venous thromboembolism.
33.2
33.2. Analysis
Comparison 33 Stripping plus elastic compression stockings (ECS) versus ECS alone, Outcome 2 Extension or recurrence (or both) of superficial thrombophlebitis.
34.1
34.1. Analysis
Comparison 34 Enzyme therapy versus placebo, Outcome 1 Pain reduction.
34.2
34.2. Analysis
Comparison 34 Enzyme therapy versus placebo, Outcome 2 Responders.
35.1
35.1. Analysis
Comparison 35 Desmin intramuscular (im) 200 versus desmin 100, Outcome 1 Adverse events.
35.2
35.2. Analysis
Comparison 35 Desmin intramuscular (im) 200 versus desmin 100, Outcome 2 Adverse drug reactions.
36.1
36.1. Analysis
Comparison 36 Desmin subcutaneous (sc) 2 × 100 versus desmin 100, Outcome 1 Adverse events.
36.2
36.2. Analysis
Comparison 36 Desmin subcutaneous (sc) 2 × 100 versus desmin 100, Outcome 2 Adverse drug reactions.
37.1
37.1. Analysis
Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 1 Pain (VAS, cm) at 3 weeks.
37.2
37.2. Analysis
Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 2 Skin erythema (cm2) at 3 weeks.
37.3
37.3. Analysis
Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 3 SF‐36 physical score at 3 weeks.
37.4
37.4. Analysis
Comparison 37 Prophylactic low molecular weight heparin (LMWH) plus elastic compression stockings (ECS) versus prophylactic LMWH, Outcome 4 SF‐36 mental score at 3 weeks.
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References

References to studies included in this review

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    1. Belcaro G, Nicolaides AN, Errichi BM, Cesarone MR, Sanctis MT, Incandela L, et al. Superficial thrombophlebitis of the legs: a randomized, controlled, follow‐up study. Angiology 1999;50(7):523‐9. - PubMed
Belcaro 2011 {published data only}
    1. Belcaro G, Cesarone MR, Dugall M, Feragalli B, Ippolito E, Corsi M, et al. Topical formulation of heparin is effective in reducing the symptoms of superficial venous thrombosis: a monocenter, observer‐blind, placebo‐controlled randomized study. Panminerva Medica 2011;53(3 Suppl 1):3‐11. - PubMed
Beyer‐Westendorf 2017 {published data only}
    1. Beyer‐Westendorf J, Schellong SM, Gerlach H, Rabe E, Weitz JI, Jersemann K, et al. Prevention of thromboembolic complications in patients with superficial‐vein thrombosis given rivaroxaban or fondaparinux: the open‐label, randomised, non‐inferiority SURPRISE phase 3b trial. Lancet Haematology 2017;4(3):e105‐13. - PubMed
    1. Werth S, Bauersachs R, Gerlach H, Rabe E, Schellong S, Beyer‐Westendorf J. Superficial vein thrombosis treated for 45 days with rivaroxaban versus fondaparinux: rationale and design of the SURPRISE trial. Journal of Thrombosis and Thrombolysis 2016;42(2):197‐204. - PubMed
Boehler 2014 {published data only}
    1. Boehler K, Kittler H, Stolkovich S, Tzaneva S. Therapeutic effect of compression stockings versus no compression on isolated superficial vein thrombosis of the legs: a randomized clinical trial. European Journal of Vascular and Endovascular Surgery 2014;48(4):465‐71. - PubMed
Cosmi 2012 {published data only}
    1. Cosmi B. Risk factors for recurrent events in subjects with superficial vein thrombosis in the randomized clinical trial SteFlux (Superficial Thromboembolism Fluxum). Thrombosis Research 2014;133(2):196‐202. - PubMed
    1. Cosmi B, Filippini M, Tonti D, Avruscio G, Ghirarduzzi A, Bucherini E, et al. A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum). Journal of Thrombosis and Haemostasis 2012;10(6):1026‐35. - PubMed
    1. Cosmi B, Filippini M, Tonti D, Ghirarduzzi A, Avruscio G, Imberti D, et al. Risk factors for recurrent events in subjects with superficial vein thrombosis in the randomized clinical trial Steflux (Superficial Thromboembolism Fluxum). Hamostaseologie 2012;32:A29. - PubMed
    1. Cosmi B, Filippini M, Tonti D, Ghirarduzzi A, Avruscio G, Imberti D, et al. The Steflux (Superficial Thromboembolism and Fluxum) randomized double blind clinical study of different treatment doses and duration of low molecular weight heparin (parnaparin) in superficial vein thrombosis. Hamostaseologie 2012;32:A28. - PubMed
Decousus 2010b {published data only}
    1. Bauersachs RM. The CALISTO‐study. Phlebologie 2011;40(2):79‐83.
    1. Decousus H. Fondaparinux reduced a composite of VTE complications or death in superficial leg‐vein thrombosis. Annals of Internal Medicine 2011;154(4):JC2‐3. - PubMed
    1. Decousus H, Prandoni P, Mismetti P, Bauersachs RM, Boda Z, Brenner B, et al. CALISTO Study Group. Fondaparinux for the treatment of superficial‐vein thrombosis in the legs. New England Journal of Medicine 2010;363(13):1222‐32. - PubMed
    1. Leizorovicz A, Becker F, Buchmuller A, Quere I, Prandoni P, Decousus H, et al. Clinical relevance of symptomatic superficial‐vein thrombosis extension: lessons from the CALISTO study. Blood 2013;122(10):1724‐9. - PubMed
    1. Leizorovicz A, Prandoni P, Decousus H. Fondaparinux reduces all types of symptomatic thromboembolic complications in patients with superficial‐vein thrombosis in the legs: data from the CALISTO study. ASH Annual Meeting Abstracts 2011;118:2310.
De Sanctis 2001 {published data only}
    1. Sanctis MT, Cesarone MR, Incandela L, Belcaro G, Griffin M. Treatment of superficial vein thrombosis with standardized application of Essaven gel ‐ a placebo‐controlled, randomized study. Angiology 2001;52 Suppl 3:S57‐62. - PubMed
Ferrari 1992 {published data only}
    1. Ferrari E, Pratesi C, Scaricabarozzi I, Trezzani R. A clinical study of efficacy and tolerability of nimesulide compared with diclofenac sodium in the treatment of acute superficial thrombophlebitis [Studio clinico sull'efficacia terapeutica e la tollerabilità della nimesulide in confronto a diclofenac sodio nel trattamento delle tromboflebiti acute superficiali]. Minerva Cardioangiologica 1992;40(11):455‐60. - PubMed
Gorski 2005 {published data only}
    1. Gorski G, Szopinski P, Michalak J, Marianowska A, Borkowski M, Geremek M, et al. Liposomal heparin spray: a new formula in adjunctive treatment of superficial venous thrombosis. Angiology 2005;56(1):9‐17. - PubMed
Holzgreve 1989 {published data only}
    1. Holzgreve A, Kleine W, Stegmann W. Local treatment of superficial thrombophlebitis with nonsteroidal antiinflammatory agents. Zeitschrift fur Allgemeinmedizin 1989;65(27):663‐7.
Incandela 2001 {published data only}
    1. Incandela L, Sanctis MT, Cesarone MR, Ricci A, Errichi BM, Dugal M, et al. Treatment of superficial vein thrombosis: clinical evaluation of essaven gel ‐ a placebo‐controlled, 8‐week, randomized study. Angiology 2001;52 Suppl 3:69‐72. - PubMed
Katzenschlager 2003 {published data only}
    1. Katzenschlager R, Ugurluoglu A, Minar E, Hirschl M. Liposomal heparin‐spraygel in comparison with subcutaneous low molecular weight heparin in patients with superficial venous thrombosis. A randomized, controlled, open multicentre study. Journal fur Kardiologie 2003;10(9):375‐8.
Koshkin 2001 {published data only}
    1. Koshkin VM, Kirienko AI. Systemic enzyme therapy in the treatment of acute thrombosis of superficial veins in the lower extremities and postthrombophlebitic disease. International Journal of Immunotherapy 2001;17(2‐4):121‐4.
Kuhlwein 1985 {published data only}
    1. Kuhlwein A. Drug treatment of superficial thrombophlebitides [Medikamentose behandlung oberflachlicher thrombophlebitiden]. Therapiewoche 1985;35(36):4067‐70.
Lozano 2003 {published data only}
    1. Lozano FS, Almazan A. Low‐molecular‐weight heparin versus saphenofemoral disconnection for the treatment of above‐knee greater saphenous thrombophlebitis: a prospective study. Vascular and Endovascular Surgery 2003;37(6):415‐20. - PubMed
Marchiori 2002 {published data only}
    1. Marchiori A, Verlato F, Sabbion P, Camporese G, Rosso F, Mosena L, et al. High versus low doses of unfractionated heparin for the treatment of superficial thrombophlebitis of the leg. A prospective, controlled, randomized study. Haematologica 2002;87(5):523‐7. - PubMed
Marshall 2001 {published data only}
    1. Marshall M, Kleine M‐W. Efficacy and tolerability of an oral enzyme therapy in the treatment of painful acute superficial thrombophlebitis [Wirksamkeit und vertraglichkeit einer oralen enzymtherapie bei der schmerzhaften akuten thrombophlebitis superficialis]. Phlebologie 2001;30(2):36‐43.
Messa 1997 {published data only}
    1. Messa G, Placa G, Puccetti L, Perri T. Heparansulphate. Effectiveness and tolerability of heparan sulphate in the treatment of superficial thrombophlebitis. Controlled clinical study vs sulodexide [Efficacia e tollerabilità dell'eparansolfato nel trattamento della tromboflebite superficiale. Studio clinico controllato vs sulodexide]. Minerva Cardioangiologica 1997;45(4):147‐53. - PubMed
Nocker 1991 {published data only}
    1. Diebschlag W, Nocker W. Lokal treatment for superficial thrombophlebitis. Die Medizinische Welt 1990;41:651‐5.
    1. Nocker W, Diebschlag W, Lehmacher W. The efficacy of a diclofenac gel compared with placebo and heparin gel in the local treatment of superficial thrombophlebitis [Lokaltherapie bei oberflachlicher thrombophlebitis. Wirksamkeit eines diclofenac‐natrium‐gels im vergleich zu placebo‐ und heparin‐gel]. Zeitschrift fur Allgemeinmedizin 1991;67:2214‐22.
Nusser 1991 {published data only}
    1. Nusser C‐J, Schare W, Bernard I. The treatment of superficial thrombophlebitis with nonsteroidal antiphlogistic agents [Therapie superfizieller thrombophlebitiden mit nichtsteroidalen antiphlogistika]. Therapiewoche 1991;41(9):541‐4.
Pinto 1992 {published data only}
    1. Pinto G, Galati D, Bompiani GD, Corcione F, Califano G, Colucci S, et al. Topical 5'‐methylthioadenosine in the treatment of symptomatic chronic venous insufficiency, haemorrhoids and superficial phlebitis. A double‐blind placebo‐controlled trial. Drug Investigation 1992;4(3):205‐14.
Rathbun 2012 {published data only}
    1. Rathbun SW, Aston CE, Whitsett TL. A randomized trial of dalteparin compared with ibuprofen for the treatment of superficial thrombophlebitis. Journal of Thrombosis and Haemostasis 2012;10(5):833‐9. - PMC - PubMed
Spirkoska 2015 {published data only}
    1. Spirkoska A, Jezovnik MK, Poredos P. Time course and the recanalization rate of superficial vein thrombosis treated with low‐molecular‐weight heparin. Angiology 2015;66:381‐6. - PubMed
Stenox Group 2003 {published data only}
    1. Superficial Thrombophlebitis Treated by Enoxaparin Study Group. A pilot randomized double‐blind comparison of a low‐molecular‐weight heparin, a nonsteroidal anti‐inflammatory agent, and placebo in the treatment of superficial vein thrombosis. Archives of Internal Medicine 2003;163(14):1657‐63. - PubMed
Titon 1994 {published data only}
    1. Titon JP, Auger D, Grange P, Hecquet JP, Remond A, Ulliac P, et al. Therapeutic management of superficial venous thrombosis with calcium nadroparin. Dosage testing and comparison with an non‐steroidal anti‐inflammatory agent [Traitement curatif des thromboses veineuses superficielles par nadroparine calcique. Recherche posologique et comparaison à un anti‐inflammatoire non stéroidien]. Annales de Cardiologie et d'Angeiologie 1994;43(3):160‐6. - PubMed
Uncu 2009 {published data only}
    1. Uncu H. A comparison of low‐molecular‐weight heparin and combined therapy of low‐molecular‐weight heparin with an anti‐inflammatory agent in the treatment of superficial vein thrombosis. Phlebology 2009;24(2):56‐60. - PubMed
Vesalio Group 2005 {published data only}
    1. Prandoni P. High versus low doses of low‐molecular‐weight heparin for the treatment of superficial vein thrombosis of the legs. A double‐blind, randomized trial. Journal of Thrombosis and Haemostasis 2005;3 (Suppl 1):Abstract number OR145. [http://onlinelibrary.wiley.com/doi/10.1111/j.1538‐7836.2005.0300b.x/full] - PubMed
    1. Prandoni P, Tormene D, Pesavento R, Vesalio Investigators Group. High vs. low doses of low‐molecular‐weight heparin for the treatment of superficial vein thrombosis of the legs: a double‐blind, randomized trial. Journal of Thrombosis and Haemostasis 2005;3(6):1152‐7. - PubMed
Winter 1986 {published data only}
    1. Winter WR, Rauhut K, Arnold S, Babiak D, Stoidner B. Local therapy of thrombophlebitis superficialis ‐ an inter‐individual comparison of Voltaren‐Emulgel versus a gel containing heparin [Lokale therapie der thrombophlebitis superficialis ‐ Ein individueller vergleich von Voltaren‐emulgel versus ein heparin‐haltiges gel]. Zeitschrift fur Rheumatologie 1986;45:180‐1.

References to studies excluded from this review

Agus 1993 {published data only}
    1. Agus GB, Angelis R, Mondani P, Moia R. Double‐blind comparison of nimesulide and diclofenac in the treatment of superficial thrombophlebitis with telethermographic assessment. Drugs 1993;46 Suppl 1:200‐3. - PubMed
Allegra 1981 {published data only}
    1. Allegra C, Pollari G, Criscuolo A, Bonifacio M, Tabassi D. Centella asiatica extract in venous disorders of the lower limbs. Comparative clinical‐instrumental trial against a placebo [L'estratto di centella asiatica nelle flebopatie degli arti inferiori. Ricerca clinico‐strumentale comparativa con un placebo]. Clinica Terapeutica 1981;99:507‐13. - PubMed
Annoni 1991 {published data only}
    1. Annoni F, Stefano A, Pabisch S, Floresta M, Magnani P, Lietti F, et al. Efficacy and safety of topical treatment with heparan sulfate in superficial phlebitis. A double‐blind placebo‐controlled trial. Acta Therapeutica 1991;17:263‐72.
Argenteri 1983 {published data only}
    1. Argenteri A, Vittori F, Longoni A. Flurbiprofen and thrombophlebitis of lower limbs: a controlled clinical trial [Terapia antiinfiammatoria delle tromboflebiti degli arti inferiori con flurbiprofen: studio clinico controllato]. Giornale Italiano di Angiologia 1983;3:203‐8.
Bagliani 1983 {published data only}
    1. Bagliani A, Rosa A, Sarchi C. A new anti‐inflammatory drug, suprofen, in the treatment of thrombophlebitis [Un nuovo farmaco antiinfiammatorio, il suprofen, nel trattamento delle tromboflebiti]. Giornale Italiano di Angiologia 1983;3:57‐64.
Becherucci 2000 {published data only}
    1. Becherucci A, Bagilet D, Marenghini J, Diab M, Biancardi H. Effect of topical and oral diclofenac on superficial thrombophlebitis caused by intravenous infusion [Efecto del diclofenaco topico y oral sobre la tromboflebitis superficial inducida por infusion intravenosa]. Medicina Clinica 2000;114(10):371‐3. - PubMed
Bergqvist 1990 {published data only}
    1. Bergqvist D, Brunkwall J, Jensen N, Persson NH. Treatment of superficial thrombophlebitis. A comparative trial between placebo, hirudoid cream and piroxicam gel. Annales Chirurgiae et Gynaecologiae 1990;79(2):92‐6. - PubMed
Bernicot 1980 {published data only}
    1. Bernicot J. The value of Eucatex in venous pathology in the young woman [Interet d'eucatex dans la pathologie veineuse de la jeune femme]. Quest Medical 1980;33(5):221‐2.
Bijuan 2003 {published data only}
    1. Bijuan L. Observation of aloe pigmentum in treatment of phlebitis. Nanfang Journal of Nursing 2003:3.
Bracale 1996 {published data only}
    1. Bracale G, Selvetella L. Controlled clinical trial comparing seaprose S to serratio‐peptidase in venous inflammatory disease. Efficacy and safety [Studio clinico sull'efficacia e la tollerabilità del seaprose S nelle flebopatie infiammatorie. Studio controllato verso serratio‐peptidasi]. Minerva Cardioangiologica 1996;44(10):515‐24. - PubMed
Bruni 1979 {published data only}
    1. Bruni M, Quarti Trevano GM, Lochis D, Baresi A, Soletti L. Double‐blind assessment of the clinical and pharmacological results of administration of a preparation with trypsin/chymotrypsin and tetracycline hydrochloride base in cases of acute phlebitis [Analisi in doppio cieco dei risultati clinici e farmacologici dopom somministrazione di un preparato a base di tripsina/chimotripsina e tetraciclina cloridrato nelle flebiti acute]. Gazzetta Medica Italiana 1979;138(11):567‐70.
Della Marchina 1989 {published data only}
    1. Della Marchina M, Renzi G, Palazzini E. Treatment of phlebopathies with low molecular weight heparin as compared to heparin calcium. Riforma Medica 1989;104(4):99‐104.
Di Perri 1986 {published data only}
    1. Perri T, Vittoria A, Messa GL, Cappelli R. Defibrotide therapy for thrombophlebitis ‐ controlled clinical trial. Haemostasis 1986;16 Suppl 1:42‐7. - PubMed
Gandhi 1984 {published data only}
    1. Gandhi DB, Palmar JR, Lewis B, Schraibman IG. Clinical comparison of elastic supports for venous diseases of the lower limbs. Postgraduate Medical Journal 1984;60:349‐52. - PMC - PubMed
Giorgetti 1990 {published data only}
    1. Giorgetti PL, Bortolani EM, Morbidelli A, Vandone PL, Ghilardi G, Mattioli A, et al. Use of a new anti‐inflammatory drug in the treatment of varicophlebitis of the lower limbs [L'uso di un nuovo farmaco antiinflammatorio nel trattamento delle varicoflebiti degli arti inferiori]. Minerva Chirurgica 1990;45(12):883‐6. - PubMed
Gouping 2003 {published data only}
    1. Gouping Z, Wan‐Er T, Xue‐Ling W, Min‐Qian X, Kun F, Turale S, et al. Notoginseny cream in the treatment of phlebitis. Journal of Infusion Nursing 2003;26(1):49‐54. - PubMed
Ibanez‐Bermudez 1996 {published data only}
    1. Ibanez‐Bermudez S, Perez Martinez F, Llamas del Castillo MD, Sevilla Jiménez JC, Gonzalez Gonzalez EM. Randomized double‐blind clinical study on the efficacy of topical sodium heparin versus sodium polysulphate pentosan [Estudio clinico randomizado y doble ciego sobre la eficacia de heparina sodica topica frente a pentosan polisulfato sodico en patologias venosas superficiales]. Farmacia Clinica 1996;13(2):110‐5.
Luttichau 1989 {published data only}
    1. Luttichau U, Palazzini E. Antithrombotic therapy in phlebopathies of lower limbs: a controlled study of low molecular weight heparin versus heparin calcium. Rivista Europea Per Le Scienze Mediche e Farmacologiche 1989;11(4):351‐8. - PubMed
Mari 1982 {published data only}
    1. Mari F, Cerreta G, Nardi V, Dialti L. Piroxicam as antiinflammatory therapy in thrombophlebitis: clinical experience [Il piroxicam nella terapia antiflogistica delle tromboflebiti. Nostra esperienza clinica]. Gazzetta Medica Italiana 1982;141(5):243‐5.
Marsala 1985 {published data only}
    1. Marsala F. A controlled double‐blind cross‐over study of a calcium heparin preparation [Studio controllato in doppio cieco cross‐over su un preparato a base di calcio‐eparina]. Clinica Terapeutica 1985;113(6):473‐7. - PubMed
Mauro 1992 {published data only}
    1. Mauro M, Ferraro G, Palmieri G. Profibrinolytic and antithrombotic effects of sulodexide oral administration: a double‐blind, cross‐over, placebo‐controlled study. Current Therapeutic Research, Clinical and Experimental 1992;51(3):342‐50.
Mehta 1975 {published data only}
    1. Mehta PP, Sagar S, Kakkar VV. Treatment of superficial thrombophlebitis: a randomized double‐blind trial of heparinoid cream. BMJ 1975;3(5984):614‐6. - PMC - PubMed
Ng 2010 {published data only}
    1. Ng IHL. Best treatment modality for superficial phlebitis. Annals of the Academy of Medicine Singapore 2010:S210.
Paciaroni 1982 {published data only}
    1. Paciaroni E, Marini M. Topical therapy for phlebophaties. Results of a controlled clinical study [Sulla terapia topica delle flebopatie. Risultati di uno studio clinico controllato]. Policlinico Sezione Medica 1982;89(3):255‐64.
Porters 1981 {published data only}
    1. Porters J, Roekaerts F, Reyntjens A. R 41 468, a specific serotonin antagonist, relieves symptoms of acute superficial thrombophlebitis. Current Therapeutic Research, Clinical and Experimental 1981;30(4):499‐506.
Pozza 1980 {published data only}
    1. Pozza E, Menghi R, Pansini GC, Duatti A, Carnovali M. Clinical trial with BPH 689 for the treatment of superficial phlebitis [Impiego clinico del BPH 689 nel trattamento delle flebiti superficiali]. Acta Chirurgica Italiana 1980;36(2):157‐66.
Rea 1981 {published data only}
    1. Rea WJ, Peters DW, Smiley RE, Edgar R, Greenberg M, Fenyves E. Recurrent environmentally triggered thrombophlebitis: a five‐year follow‐up. Annals of Allergy 1981;47(5):338‐44. - PubMed
Resta 1967 {published data only}
    1. Resta V. Clinical comparative experiment on 2 ointments of different extractive heparinoid concentrations (double blind test). Arzneimittel‐Forschung 1967;17(8):1078‐82. - PubMed
Rozsos 1994 {unpublished data only}
    1. Rozsos I, Kollar L, Scholz ME. The topical treatment of infusion thrombophlebitis with pentosan polysulfate sodium ointment. A randomised double‐blind study. Annals of Hematology 1994;68 Suppl 1:A92.
Seccia 1989 {published data only}
    1. Seccia M, Bortolotti P, Bellomini MG, Buccianti P, Chiarugi M, Cavina E. Use of defibrotide in the treatment of acute superficial thrombophlebitis of the legs [Impiego del defibrotide nel trattamento delle tromboflebiti acute superficiali degli arti]. Minerva Chirurgica 1989;44(9):1379‐84. - PubMed
Seghezzi 1972 {published data only}
    1. Seghezzi R, Borri P, Chierichetti S, Ferrari P. Controlled clinical trial of 4‐prenyl‐1,2‐diphenyl‐3,5‐pyrazolidinedione (DA2370) and oxyphenbutazone in thrombophlebitis. Arzneimittel‐Forschung 1972;22(1):272‐4. - PubMed
Seligman 1969 {published data only}
    1. Seligman B. Oral bromelains as adjuncts in the treatment of acute thrombophlebitis. Angiology 1969;20(1):22‐6. - PubMed
Stolle 1986 {published data only}
    1. Stolle A. Treatment of superficial thrombophlebitis with a new emulsion gel [Behandlung der thrombophlebitis superficialis mit einem neuartigen emulsiongel]. Die Medizinische Welt 1986;37:700‐2.
Supe 2013 {published data only}
    1. Supe A, Subnis BM, Rajeev RM, Panchal VH, Lakhani RJ, Mehtalia B, et al. Novel topical quick penetrating solution of heparin in management of superficial thrombophlebitis: results of randomized active controlled trial. International Journal of Pharmaceutical Sciences and Research 2013;4(11):4442‐7.
Tomamichel 1983 {published data only}
    1. Tomamichel M, Reiner M. Treatment of thrombophlebitis and superficial phlebitis. A comparison of nimesulide and oxyphenbutazone. Clinical Trials Journal 1983;20(3):148‐57.
van Cauwenberge 1972 {published data only}
    1. Cauwenberge H. Double‐blind study of the efficacy of a soluble rutoside derivative in the treatment of venous disease [Etude n double aveugle de l'efficacité de l'O‐(beta‐hydroxyéthyl)‐rutosides dans le traitement des affections veineuses]. Archives Internationales de Pharmacodynamie et de Therapie 1972;196:122‐8. - PubMed
van der Knaap 1988 {published data only}
    1. Knaap JH, Ottolander GJH, Heerde LR. Research into efficacy of heparinoid cream [Onderzoek naar de effectiviteit van heparinodezalf]. Pharmaceutisch Weekblad 1988;123:973‐5.

References to studies awaiting assessment

Cazaubon 2013 {published data only}
    1. Cazaubon M. Effects of progressive versus degressive elastic compression stockings on superficial and deep veins of the calf. Angeiologie 2013;65:39‐47.
Wac 2001 {published data only}
    1. Wac ZX. Observation of the effect of Honghua injection in treating superficial thrombotic phlebitis. Chinese Journal of Information on Traditional Chinese Medicine 2001;8:60‐1.
Xu 2001 {published data only}
    1. Xu BH, Tang L, Tang WJ, Peng JH, Zheng WP, Peng JX. Clinical observation of Mai Luo Tong Granule for treating thrombophlebitis. Chinese Journal of Information on Traditional Chinese Medicine 2001;8:69.

References to ongoing studies

Rabe 2009 {published data only}
    1. Rabe E. DAPS‐dalteparin in patients with superficial leg vein phlebitis in addition to compression treatment ‐ a placebo‐controlled phase‐III study. XVIth World Meeting of the Union Internationale de Phlébologie (UIP); 2009 Aug 31‐Sept 4; Principality of Monaco.

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References to other published versions of this review

Di Nisio 2007a
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Di Nisio 2012
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Di Nisio 2013
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