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

Terminated

Phase 3 Results N/A

Trial Description

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

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.

Trial Stopped: early discontinuation based on strategic sponsor decision not driven by any safety concern

Conditions

Interventions

  • Warfarin (Coumadin®)Drug
    Intervention Desc: Capsules with 1 or 5 mg for INR-adjusted dose (INR checked at least once a month) Oral administration
    ARM 1: Kind: Experimental
    Label: 2
    ARM 2: Kind: Experimental
    Label: Warfarin
    Description: Warfarin, INR-adjusted dose, for a minimum total treatment duration of 6 months.
  • SSR126517E "biotinylated idraparinux" Drug
    Intervention Desc: once-weekly subcutaneous injection
    ARM 1: Kind: Experimental
    Label: 1
  • Idrabiotaparinux Drug
    Other Names: SSR126517; Biotinylated idraparinux
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: Idrabiotaparinux
    Description: Idrabiotaparinux, 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).
  • Placebo (for idrabiotaparinux) Drug
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: Warfarin
    Description: Warfarin, INR-adjusted dose, for a minimum total treatment duration of 6 months.
  • Placebo (for warfarin) Drug
    Intervention Desc: Warfarin matching capsules Oral administration
    ARM 1: Kind: Experimental
    Label: Idrabiotaparinux
    Description: Idrabiotaparinux, 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).
  • Avidin Drug
    Other Names: SSR29261
    Intervention Desc: Vial containing 105 mg of lyophilized powder for dilution Intravenous infusion for 30 minutes
    ARM 1: Kind: Experimental
    Label: Idrabiotaparinux
    Description: Idrabiotaparinux, 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).
  • Placebo (for avidin) Drug
    Intervention Desc: Vial containing 105 mg of matching lyophilized powder for dissolution Intravenous infusion for 30 minutes
    ARM 1: Kind: Experimental
    Label: Warfarin
    Description: Warfarin, INR-adjusted dose, for a minimum total treatment duration of 6 months.
  • Idrabiotaparinux sodium Drug
    Other Names: SSR126517; Biotinylated idraparinux
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: Idrabiotaparinux
    Description: 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).

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Prevention
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary composite of all strokes or non central nervous system (CNS) systemic embolic events (SE) end of study No
Secondary separate components of the primary study outcome end of study No
Secondary composite (stroke or non CNS SE or major bleeding or death) end of study No
Primary 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) No
Secondary Components of the primary study outcome measure: From randomization up to the end of the treatment period (minimum of 6 months) No
Secondary 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) No

Sponsors