Evaluation of Weekly Idrabiotaparinux Sodium Versus Oral Adjusted-dose Warfarin to Prevent Stroke and Systemic Thromboembolic Events in Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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The objective is to evaluate whether once weekly subcutaneous (SC) injection of idrabiotaparinux sodium (biotinylated idraparinux) is at least as efficient to prevent clots in brain and in the other organs than oral international normalized ratio (INR) adjusted-dose warfarin in patients with atrial fibrillation (AF).

Detailed Description
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The end of the study is defined by a common study end date for all participants, defined as 9 months (39 weeks) after the last participant randomized. All participants will receive oral warfarin (or matching placebo) and weekly SC injections of idrabiotaparinux sodium (or matching placebo) up to 6 months before the common study end date. All participants are expected to be treated for at least 6 months. All participants will have then an 6-month observational period after cessation of study treatment.

Official Title
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A Multicenter, Randomized, Double-blind, Assessor-blind, Non-inferiority Study Comparing the Efficacy and Safety of Once-weekly Subcutaneous Biotinylated Idraparinux (SSR126517E) With Oral Adjusted-dose Warfarin in the Prevention of Stroke and Systemic Thromboembolic Events in Patients With Atrial Fibrillation

Conditions
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Atrial Fibrillation

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non valvular atrial fibrillation (AF) Indication for long-term Vitamin-K antagonist (VKA) therapy based on the presence of previous ischemic stroke, transient ischemic attack (TIA) or systemic embolism and/or at least two of the following risk factors: hypertension requiring drug treatment, moderately or severely impaired left ventricular function and/or congestive heart failure, age > or = 75 years, diabetes mellitus. Main exclusion Criteria: Indication for VKA other than AF Stroke or TIA within previous 5 days Transient AF caused by a reversible disorder Planned major surgery/trauma or cardioversion within 30 days INR > 3 at baseline Active bleeding or high risk of bleeding Uncontrolled hypertension Pregnancy or childbearing potential without proper contraceptive measures or breast feeding.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idrabiotaparinux<br>Idrabiotaparinux sodium, 3.0 mg, once-weekly for 7 weeks followed a maintenance dosing adjusted according to the age and to the renal function for a minimum total treatment duration of 6 months. 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 overdosage). | Drug: Idrabiotaparinux sodium<br>* Pre-filled syringes containing: 0.5 mL for the 3.0 mg dosage; 0.33 mL for the 2.0 mg dosage (maintenance dosage for participants with mild renal impairment and less than 75 years old); 0.25 mL for the 1.5 mg dosage (maintenance dosage for participants with moderate renal impairment or age ≥75 years). Subcutaneous injection<br>* Other names: Biotinylated idraparinux;Drug: Placebo (for warfarin)<br>* Warfarin matching capsules Oral administration<br>Drug: Avidin<br>* Vial containing 105 mg of lyophilized powder for dilution Intravenous infusion for 30 minutes<br>* Other names: SSR29261;|
| Active Comparator: Warfarin<br>Warfarin, INR-adjusted dose, for a minimum total treatment duration of 6 months. | 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)<br>* Matching pre-filled syringes containing: 0.5 mL for the 3.0 mg dosage; 0.33 mL for the 2.0 mg dosage (maintenance dosage for participants with mild renal impairment and less than 75 years old); 0.25 mL for the 1.5 mg dosage (maintenance dosage for participants with moderate renal impairment or age ≥75 years). Subcutaneous injection<br>Drug: Placebo (for avidin)<br>* Vial containing 105 mg of matching lyophilized powder for dissolution Intravenous infusion for 30 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all fatal or non-fatal strokes or non central nervous system (CNS) systemic embolic events (SE) |  | From randomization up to the end of the treatment period (minimum of 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Components of the primary study outcome measure: |  | From randomization up to the end of the treatment period (minimum of 6 months) | 
| Composite of stroke or non CNS SE or myocardial infarction (MI) or venous thromboembolism (VTE) or major bleeding or death |  | From randomization up to the end of the treatment period (minimum of 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, systemic thromboembolic events