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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An International, Multicenter, Randomized, Double-blind, Double-dummy, Parallel Group, Study of 3-month or 6-month Treatment With SSR126517E (3.0 mg s.c. Once-weekly) Versus Oral INR-adjusted Warfarin in the Treatment of Patients With Symptomatic Pulmonary Embolism With or Without Symptomatic Deep Venous Thrombosis

Conditions
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Embolism, Thrombosis

Intervention / Treatment
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* Drug: Idrabiotaparinux sodium
* Drug: Warfarin
* Drug: Placebo (for idrabiotaparinux sodium)
* Drug: Avidin
* Drug: Placebo (for warfarin)
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idrabiotaparinux<br>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). | Drug: Idrabiotaparinux sodium<br>* 0.5 mL pre-filled syringe for 3.0 mg Subcutaneous injection<br>* Other names: SSR126517;Drug: Avidin<br>* 100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes<br>* Other names: SSR29261;Drug: Placebo (for warfarin)<br>* Warfarin matching capsules Oral administration<br>Drug: Enoxaparin<br>* Prefilled syringes as locally registered Subcutaneous injection<br>|
| Active Comparator: Warfarin<br>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). | Drug: Warfarin<br>* Capsules with 1 or 5 mg for INR-adjusted dose (INR checked at least once a month) Oral administration<br>Drug: Placebo (for idrabiotaparinux sodium)<br>* 0.5 mL pre-filled syringe Subcutaneous injection<br>Drug: Avidin<br>* 100 mg in 10 mg/mL solution Intravenous infusion for 30 minutes<br>* Other names: SSR29261;Drug: Enoxaparin<br>* Prefilled syringes as locally registered Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of symptomatic, fatal or not, VTE (PE or DVT) as confirmed by a Central Independent Adjudication Committee (CIAC) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep venous thrombosis, pulmonary embolism, anticoagulant drugs