PETRO Stroke Prevention in Patients With AF by Treatment With Dabigatran, With and Without Aspirin, Compared to Warfarin

Completed

Phase 2 Results

Trial Description

The purpose of this trial is to evaluate the safety of different doses of BIBR 1048, alone or in combination with acetylsalicylic acid (ASA), as determined by the rates of bleeding and other adverse events.
A secondary objective of this trial is to evaluate the anticoagulant effect of different doses of BIBR 1048, based on the reduction of plasma concentrations of D-dimer, a laboratory marker for activated coagulation in patients with atrial fibrillation (AF), and to correlate bleeding and other events with pharmacokinetic (PK) and pharmacodynamic (PD) data.

Conditions

Interventions

  • Warfarin (Coumadin┬«)Drug
    Intervention Desc: comparator
    ARM 1: Kind: Experimental
    Label: warfarin
    Description: once daily, dosed to target International Normalised Ratio (INR) 2.0 to 3.0
  • Dabigatran with ASA Drug
    Intervention Desc: dose comparison in combination
    ARM 1: Kind: Experimental
    Label: dabigatran 50 mg bid + 81 mg ASA qd
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. Acetylsalicylic acid (ASA) once daily (quaque dies = qd) in the morning.
    ARM 2: Kind: Experimental
    Label: dabigatran 50 mg bid + 325 mg ASA qd
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
    ARM 3: Kind: Experimental
    Label: dabigatran 150 mg bid + 81 mg ASA qd
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
    ARM 4: Kind: Experimental
    Label: dabigatran 150 mg bid + 325 mg ASA qd
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
    ARM 5: Kind: Experimental
    Label: dabigatran 300 mg bid + 81 mg ASA qd
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
    ARM 6: Kind: Experimental
    Label: dabigatran 300 mg bid + 325 mg ASA qd
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
  • Dabigatran without ASA Drug
    Intervention Desc: dose comparison
    ARM 1: Kind: Experimental
    Label: dabigatran 50 mg twice daily (bid)
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening. Twice daily (bis in die = bid).
    ARM 2: Kind: Experimental
    Label: dabigatran 150 mg bid
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening
    ARM 3: Kind: Experimental
    Label: dabigatran 300 mg bid
    Description: Dabigatran: one capsule in the morning and 1 capsule in the evening

Trial Design

  • Allocation: Randomized
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Number of Participants With Fatal or Life-threatening Major Bleeding Events 12 weeks Yes
Primary Number of Participants With Minor/Relevant Bleeding Events 12 weeks Yes
Primary Number of Participants With Minor/Nuisance Bleeding Events 12 weeks Yes
Secondary Number of Participants With Thromboembolic Events: Composite Endpoint 12 weeks No
Secondary Number of Participants With Thromboembolic Events: Ischemic Stroke 12 weeks No
Secondary Thromboembolic Events: Number of Participants With Transient Ischemic Attack 12 weeks No
Secondary Thromboembolic Events: Number of Participants With Systemic Thromboembolism 12 weeks No
Secondary Thromboembolic Events: Number of Participants With Myocardial Infarction 12 weeks No
Secondary Thromboembolic Events: Number of Participants With Other Major Cardiac Events 12 weeks No
Secondary Thromboembolic Events: Number of Participants Who Died 12 weeks No
Secondary D-dimer: Difference From Baseline baseline and 12 weeks No
Secondary Soluble Fibrin: Difference From Baseline baseline and 12 weeks No
Secondary 11-dehydrothromboxane B2 (TXB2): Difference From Baseline baseline and 12 weeks No
Secondary Ecarin Clotting Time (ECT): Difference From Baseline baseline and 12 weeks No
Secondary Activated Partial Thromboplastin Time (aPTT): Difference From Baseline baseline and 12 weeks No
Secondary Trough Plasma Concentration of Dabigatran (BIBR 953) 12 weeks No
Secondary Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline 12 weeks Yes
Secondary Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline 12 weeks Yes
Secondary Number of Participants With Increase of Bilirubin to >2*Baseline 12 weeks Yes
Secondary Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline 12 weeks Yes
Secondary Severity of Adverse Events 12 weeks No

Sponsors