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Clinical Study Assessing Idrabiotaparinux Sodium Injections Once-weekly in Pulmonary Embolism Therapeutic Approach

Phase 3
Completed
Conditions
Thrombosis
Embolism
Interventions
Drug: Placebo (for idrabiotaparinux sodium)
Drug: Placebo (for warfarin)
Registration Number
NCT00345618
Lead Sponsor
Sanofi
Brief Summary

Objectives are to evaluate whether idrabiotaparinux sodium (SSR126517E) is as least as effective as a standard warfarin treatment to prevent recurrence of venous thromboembolic events (VTE) in patients with symptomatic pulmonary embolism (PE) with or without symptomatic deep venous thrombosis (DVT) and to assess its safety (bleedings) versus warfarin.

Detailed Description

Treatment with a therapeutic dose of any low molecular weight heparin (LMWH) or unfractioned heparin (UFH) or fondaparinux is allowed only within the 36 hours immediately preceding randomization. Randomization is performed as soon as the diagnosis of PE (and DVT if concomitant suspected symptomatic DVT) is confirmed.

Allocation to treatment is done centrally by Interactive Voice Response System (IVRS) and stratified by (1) center, (2) intended treatment duration, ie, 3 months or 6 months. At randomization, the planned duration of treatment (3 or 6 months) is prespecified by the Investigator and determined on the assessment of risk of VTE recurrence. Participants are randomized to either idrabiotaparinux + placebo of warfarin, or warfarin + placebo of idrabiotaparinux, with an initial treatment of at least 5 days with enoxaparin in both treatment groups.

Participants in the 3-month stratum have an additional 13-week observational period after cessation of study treatment. Participants in the 6-month stratum have a 13-week up to 26-week observational period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
3202
Inclusion Criteria
  • Symptomatic pulmonary embolism with or without symptomatic deep vein thrombosis
Exclusion Criteria
  • End stage renal failure, hepatic failure, uncontrolled hypertension;
  • Active bleeding or high risk for bleeding;
  • Pregnancy or childbearing potential without proper contraceptive measures, threatened abortion.
  • Breastfeeding.
  • Known allergy to idraparinux or idrabiotaparinux, avidin or egg proteins;
  • hypersensitivity to warfarin, enoxaparin, heparin or pork product; or any other contraindication listed in the labelling of warfarin or enoxaparin;
  • Indication of prolonged anticoagulation therapy for other reason than PE;
  • Life expectancy < 6 months;

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
IdrabiotaparinuxAvidinIdrabiotaparinux sodium, 3.0 mg, once-weekly for 3 or 6 months depending on the stratum, after enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
IdrabiotaparinuxPlacebo (for warfarin)Idrabiotaparinux sodium, 3.0 mg, once-weekly for 3 or 6 months depending on the stratum, after enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
WarfarinPlacebo (for idrabiotaparinux sodium)Warfarin, INR-adjusted dose, started 24 hours after the start of enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days, and continued for 3 or 6 months depending on the stratum. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
IdrabiotaparinuxIdrabiotaparinux sodiumIdrabiotaparinux sodium, 3.0 mg, once-weekly for 3 or 6 months depending on the stratum, after enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
IdrabiotaparinuxEnoxaparinIdrabiotaparinux sodium, 3.0 mg, once-weekly for 3 or 6 months depending on the stratum, after enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
WarfarinWarfarinWarfarin, INR-adjusted dose, started 24 hours after the start of enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days, and continued for 3 or 6 months depending on the stratum. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
WarfarinEnoxaparinWarfarin, INR-adjusted dose, started 24 hours after the start of enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days, and continued for 3 or 6 months depending on the stratum. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
WarfarinAvidinWarfarin, INR-adjusted dose, started 24 hours after the start of enoxaparin, 1.0 mg/kg, every 12 hours for at least 5 days, and continued for 3 or 6 months depending on the stratum. Avidin, 100 mg, at the discretion of the investigator whenever deemed appropriate and possible (ie, life-threatening bleeding, emergency invasive procedure with the potential of uncontrolled bleeding, or over-dosage).
Primary Outcome Measures
NameTimeMethod
Recurrence of symptomatic, fatal or not, VTE (PE or DVT) as confirmed by a Central Independent Adjudication Committee (CIAC)3 months
Secondary Outcome Measures
NameTimeMethod
Recurrence of symptomatic, fatal or not, VTE (PE or DVT) as confirmed by a Central Independent Adjudication Committee (CIAC)6 months
Incidence of any clinically relevant bleeding as classified by the CIAC (ie, major bleeding and other clinically relevant non major bleeding)3 months, 6 months and 3- to 6-month post-treatment follow-up

Trial Locations

Locations (4)

Sanofi-Aventis Admnistrative Office

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Moscow, Russian Federation

Sanofi-Aventis Administrative Office

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Guildford Surrey, United Kingdom

sanofi-aventis Australia & New Zealand administrative office

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Macquarie Park, New South Wales, Australia

Sanofi-Aventis Administraive Office

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Puerto Rico, Puerto Rico

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