Efficacy of Low Molecular Weight Heparin in Superficial Vein Thrombosis (REVETR)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Prospective, Randomized, Double-blinded Trial of the Efficacy and Safety of Different Doses and Duration of Low Molecular Weight Heparin (Dalteparin) in Superficial Vein Thrombosis|
- To assess the efficacy and safety of low-molecular-weight heparin - dalteparin in patients with ST [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]To compare the efficacy of therapeutic vs. preventive doses of dalteparin in prevention of thromboembolic complications and disease progression in patients with acute thrombophlebitis of lower extremities
- Combined end-point: occurrence of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism or ultrasonographic blood clot progression or relapse of ST [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Clinically relevant bleeding occurring [ Time Frame: during treatment ] [ Designated as safety issue: Yes ](i.e., major or clinically relevant non-major bleeding)
- To investigate the safety of ST treatment with preventive doses of dalteparin compared with therapeutic doses, death, bleeding, HIT [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- To ascertain whether the extent or progression of ST is related to systemic inflammatory parameters [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- To study a possible correlation between effectiveness of treatment of ST with preventive and therapeutic doses of dalteparin and severity of systemic inflammatory parameters. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- To determine whether the extension of anticoagulant treatment with the study drug for additional six weeks is more effective and safer [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||November 2012|
|Estimated Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
|Active Comparator: dalteparin 5000 I.U./24 h s.c.||
dalteparin 5000 I.U./24 h s.c. for 6 weeks
Other Name: Fragmin
|Active Comparator: dalteparin 15000 I.U./24 h s.c.||
dalteparin 15000 I.U./24 h s.c. for 6 weeks
Other Name: Fragmin
Until recently thrombophlebitis was regarded as a benign and self-limiting disease. Recent studies have shown that various complications, especially vein thrombosis and pulmonary thromboembolism, often accompany ST. An observational study (Prospective Observational Superficial Thrombophlebitis - POST) showed that three months after onset of the disease thromboembolic events occurred in 10% of patients: pulmonary embolism in 0.4%, disease progression in 3.1% and disease recurrence in 1.9% of patients. Therefore, ST is now frequently regarded as a part of the thromboembolic syndrome. On the basis of the evidence referred to above anticoagulants, especially heparin, are used more and more often for treatment of ST instead of anti-inflammatory drugs and non-steroidal antirheumatics. Several studies performed so far have examined efficacy of standard and low-molecular-weight heparin in various doses, but no final conclusion on the efficacy of treatment of ST with heparin has been established yet.
A study by Marchiori and colleagues showed that 8-12-day treatment of ST with preventive and therapeutic doses of low-molecular-weight heparin significantly reduces progression and relapse of the disease, but not its thromboembolic complications. Another study demonstrated that low-molecular-weight heparin in combination with elastic compression was not significantly more effective than compression alone. Comparison of preventive and therapeutic doses of low-molecular-weight heparin given to patients over the period of one month after disease onset showed no differences in the efficacy in prevention of disease progression and thromboembolic complications. The standard (unfractionated) heparin was also shown to be effective in preventing disease progression, however, but not in preventing thromboembolic complications. It is also not clear how long the treatment with heparin should last. So far only one study compared the efficacy of treatment with various doses of low-molecular-weight heparin from one month to three months' duration; it demonstrated that 1-month treatment with lower doses of heparin was as effective as 3-month treatment with therapeutic doses of heparin. A recent study (CALISTO) compared efficacy of preventive doses of fondaparinux (2.5 mg) with placebo in more than 3,000 patients with ST and concluded that anticoagulant treatment of ST probably does not significantly influence prevention of thromboembolic complications (Abstract presented at the 5th ASA Annual Meeting of the American Society of Hematology).
Results of recent studies therefore show that heparin (standard or low-molecular-weight heparin) in various doses prevents ST progression, but no final agreement has emerged as to whether they prevent occurrence of thromboembolic complications as well. Interpretation of the results is difficult because of the heterogeneity of the patients included in certain studies and especially because of unavailability of subgroup analyses, which would help to establish whether treatment with heparin is more effective in certain groups of patients with ST than in those with presenting forms of the disease. Latest (2008) guidelines for prevention of venous thromboembolic events adopted by the American College of Chest Physicians (ACCP) recommend treatment with at least preventive or median doses of low-molecular-weight heparin or standard heparin for the duration of not less than 4 weeks. This recommendation is based on a very low evidence level (level 2B).
In this study the investigators will therefore try to ascertain whether the extensiveness of thrombophlebitis and the distance of the end of blood clot from saphenofemoral and saphenopopliteal junction influence the efficacy of ST treatment with heparin. The investigators shall also monitor the expression of systemic inflammatory parameters that might be related to the efficacy of the treatment and progression of the disease.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01245998
|University Medical Centre Ljubljana|
|Ljubljana, Slovenia, 1000|
|Principal Investigator:||Pavel Poredos, M.D., Ph.D.||University Medical Centre Ljubljana, Department of Vascular Disease|