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Randomized Controlled Trial of Anticoagulation vs. Placebo for a First Symptomatic Isolated Distal Deep-vein Thrombosis (IDDVT)

Phase 3
Completed
Conditions
Distal (Calf) Deep-vein Thrombosis
Interventions
Registration Number
NCT00421538
Lead Sponsor
University Hospital, Geneva
Brief Summary

CACTUS-PTS is a randomized, placebo-controlled, double-blind study which aims primarily to determine the effectiveness of a 6 week course of therapeutic-dose LMWH (nadroparine) injections vs. placebo in patients with a first symptomatic isolated distal (calf) deep-vein thrombosis (IDDVT), as measured by rate of proximal DVT and symptomatic PE at 6 weeks. Additionally, the study aims to determine if the 6 week course of treatment with therapeutic-dose LMWH (nadroparine) injections, compared to placebo, decreases the frequency of post-thrombotic syndrome (PTS) at 1 year.

Detailed Description

The CACTUS-PTS study will compare anticoagulant treatment for 6 weeks versus placebo in acute, symptomatic distal DVT. Patients will be randomized to receive either a six-week period of LMWH at therapeutic dosage or a six-week period of placebo. All patients will be treated with elastic compression stockings and followed-up with a standardized ultrasonography protocol. Strict ultrasonographic diagnostic criteria for distal DVT have been defined. Control compression ultrasonography will be performed between days 3 and 7 and at six weeks after inclusion. The primary outcome will be a composite of the proportion of patients with extension of the thrombus to the proximal veins (detected by the programmed ultrasound examinations or by an ultrasound performed because of recurrent symptoms) or symptomatic PE in both arms of the study during the 6-weeks study period. Patients with such an outcome will be anticoagulated as currently admitted in presence of a proximal DVT. Secondary outcomes will be the individual components of the composite endpoint (distal DVT extension to proximal veins; symptomatic PE), major bleeding, serious adverse events and death reported at 6 weeks and 90 days. To answer the research question of the PTS add-on study, patients will self-assess and be assessed for PTS by a clinician using the Villalta scale, 1 year following their enrolment into the trial. In addition, patients will complete a Quality of Life (QOL) questionnaire. The QOL questionnaire will be comprised of both the VEINES-QOL and SF-36. The primary outcome is the rate of PTS, with secondary outcomes of QOL scores and PTS severity.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
260
Inclusion Criteria
  • All outpatients with an acute, symptomatic, distal DVT will be included in the study, provided they correspond to the following diagnostic and exclusion criteria, and they have signed an informed consent form.
Exclusion Criteria
  • Age less than 18 years
  • Previously objectively diagnosed DVT or PE
  • Distal DVT involving the tibioperoneal trunk (i.e. calf trifurcation)
  • Clinically suspected pulmonary embolism
  • Active cancer, receiving cancer treatment or cancer considered cured for <6 months
  • Ipsilateral or contralateral proximal DVT
  • Indication for long-term anticoagulation (e.g. atrial fibrillation, mechanical heart valve...)
  • Pregnancy
  • Thrombocytopenia (platelet count < 100 g/l)
  • Impaired renal function (serum creatinine > 180 micromol/l or clearance to creatinine less than 30 ml/min)
  • Known hypersensitivity to heparin
  • Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (gastric ulcer, cerebral malignant disease...)
  • Treatment with daily NSAIDs (aspirin ≤160 mg/day permitted)
  • Body weight >115 kg or <40 kg
  • Treatment with therapeutic doses of anticoagulants for >2 days, corresponding to: 2 injections of LMWH if once daily therapeutic LMWH used; 3 injections of LMWH if twice-daily therapeutic LMWH used; 1 dose of oral vitamin K antagonist (e.g. warfarin)
  • Ongoing requirement for prophylactic dose thromboprophylaxis (e.g. acute post-op patient receiving thromboprophylaxis)
  • Enrolled in another clinical trial within previous 30 days
  • Inability or refusal to provide informed consent

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboInjectable placebo
LMWHnadroparine calciumTherapeutic dose of Nadroparin
Primary Outcome Measures
NameTimeMethod
Rate of post-thrombotic syndrome (PTS)1 year

Rate of post-thrombotic syndrome (PTS) diagnosed using the Villalta scale.

Composite of rate of extension of distal DVT to proximal deep veins (includes ipsilateral extension or new contralateral proximal DVT) or symptomatic PE at 6 weeks6 weeks
Secondary Outcome Measures
NameTimeMethod
PTS severity category1 year

Can either be mild, intermediate, severe

Death at 6 weeks and 90 days6 weeks and 3 months
Major bleeding at 6 weeks and 90 days6 weeks and 3 months
Serious adverse events at 6 weeks and 90 days6 weeks and 3 months
Individual components of the composite endpoint: distal DVT extension to proximal veins at 6 weeks and 90 days; PE at 6 weeks and 90 days6 weeks and 3 months
Generic and venous disease-specific Quality of Life scores1 year

Trial Locations

Locations (7)

Royal University Hospital

🇨🇦

Saskatoon, Saskatchewan, Canada

Montpellier University Hospital

🇫🇷

Montpellier, Languedoc, France

Hamilton General Hospital

🇨🇦

Hamilton, Ontario, Canada

Hopital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Ottawa General Hospital

🇨🇦

Ottawa, Ontario, Canada

University Hospital of Geneva

🇨🇭

Geneva, Switzerland

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