Efficacy of Low Molecular Weight Heparin in Superficial Vein Thrombosis
Condition: Superficial Thrombophlebitis
MeSH terms: Thrombosis; Venous Thrombosis; Thrombophlebitis
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the study is to establish whether treatment of superficial vein thrombosis (SVT)
      with low-molecular-weight heparin in preventive or therapeutic doses prevents disease
      progression and thromboembolic events (deep vein thrombosis and pulmonary embolism), whether
      efficacy of low-molecular-weight heparin differs with regard to the dosage used (prevention,
      treatment), and to recognize groups of patients in which treatment with heparin is most
      efficient, as well as to determine factors that influence the efficacy of SVT treatment with
      heparin.
    

Detailed description: 
      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 SVT. 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, SVT 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 SVT instead of anti-inflammatory drugs and non-steroidal antirheumatics. Several
      studies performed so far have examined the efficacy of standard and low-molecular-weight
      heparin in various doses, but no final conclusion on the efficacy of treatment of SVT with
      heparin has been established yet.

      A study by Marchiori and colleagues showed that 8-12-day treatment of SVT 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 the efficacy of preventive doses of fondaparinux
      (2.5 mg) with placebo in more than 3,000 patients with SVT and concluded that anticoagulant
      treatment of SVT probably does not significantly influence prevention of thromboembolic
      complications (Abstract presented at the 5th Annual Meeting of the American Society of
      Hematology).

      Results of recent studies show that heparin (standard or low-molecular-weight heparin) in
      various doses prevents SVT progression, but no final agreement has emerged as to whether they
      prevent the occurrence of thromboembolic complications. 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 SVT 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 was based
      on a very low evidence level (level 2B).

      In this study, we aim to investigate whether the extensiveness of thrombophlebitis and the
      proximal distance of the end of a blood clot from saphenofemoral and saphenopopliteal
      junction influence the efficacy of SVT 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.
    

Intervention name(s): Dalteparin; Dalteparin
Intervention type(s): Drug; Drug
Intervention description(s): dalteparin 5000 I.U./24 h s.c. for 6 weeks; dalteparin 15000 I.U./24 h s.c. for 6 weeks
Other intervention name(s): Fragmin; Fragmin
Intervention MeSH terms: Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Thrombophlebitis; Venous thrombosis; Pulmonary embolism; Anticoagulants; Low-Molecular-Weight Heparin