PETRO Stroke Prevention in Patients With AF by Treatment With Dabigatran, With and Without Aspirin, Compared to Warfarin
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: dabigatran with ASA; dabigatran with ASA; dabigatran with ASA; dabigatran with ASA; dabigatran with ASA; dabigatran with ASA; warfarin; dabigatran without ASA; dabigatran without ASA; dabigatran without ASA
Intervention description: dose comparison in combination; dose comparison in combination; dose comparison in combination; dose comparison in combination; dose comparison in combination; dose comparison in combination; comparator; dose comparison; dose comparison; dose comparison
Intervention MeSH terms: Warfarin; Dabigatran
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Enrollment: 502.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion criteria

          1. Non-rheumatic atrial fibrillation.

          2. Coronary artery disease (CAD), documented by previous myocard infarction (MI), angina,
             positive stress test, previous coronary intervention or bypass surgery, or
             atherosclerotic lesion(s) diagnosed by coronary angiography) is only considered as one
             of several possible qualifying risk factors. After recruitment of ca. 30%, a protocol
             amendment 4 was issued so that CAD was only considered as one of several possible
             qualifying risk factors, 2. see (3 f) below.

          3. An additional risk factor for stroke, i.e. one or more of the following
             conditions/events:

               1. hypertension (defined as systolic bloodpressure (SBP) > 140 mmHg and/or diastolic
                  bloodpressure (DBP) > 90 mm Hg) requiring antihypertensive medical treatment.

               2. diabetes mellitus (type I and II).

               3. symptomatic heart failure or left ventricular dysfunction (ejection fraction (EF)
                  < 40%).

               4. a previous ischemic stroke or transient ischemic attack.

               5. age greater than 75 years.

               6. history of coronary artery disease (by amendment 4)

          4. Treatment with warfarin or other vitamin K dependent anticoagulants for at least 8
             weeks prior to inclusion. International normalised ratio (INR) should be within
             therapeutic range (i.e. INR 2.0 - 3.0) at visit 1 otherwise the visit should be
             rescheduled.

          5. Age > = 18 years at entry.

          6. Written, informed consent.

        Exclusion criteria

          1. Valvular heart disease.

          2. Planned cardioversion.

          3. Recent (=< 1 month) myocardial infarction, stroke or transient ischemic attack (TIA),
             or patients who have received a coronary stent within the last 6 months.

          4. Intolerance or contraindications to acetylsalicylic acid (ASA).

          5. Any contraindication to anticoagulant therapy.

          6. Major bleeding within the last 6 months (other than gastrointestinal (GI) hemorrhage).

          7. Severe renal impairment (estimated glomerular filtration rate (GFR) =< 30 mL/min).

          8. Uncontrolled hypertension (SBP > 180 mmHg and/or DBP > 100 mmHg).

          9. Abnormal liver function as defined by aspartat-aminotransferase (AST),
             alanin-aminotransferase (ALT), serum bilirubin or alkaline phosphatase (AP) above the
             reference range, or history of liver disease.

         10. Women who are pregnant or of childbearing potential who refuses to use a medically
             acceptable form of contraception throughout the study.

         11. Patients who have received an investigational drug within the last 30 days.

         12. Patients scheduled for major surgery or invasive procedures which may cause bleeding,
             or those who have had major surgery or percutaneous coronary intervention (PCI) within
             6 weeks.

         13. Patients considered unreliable by the investigator.

         14. Another indication for anticoagulant treatment.

         15. Patients suffering from anemia.

         16. Patients suffering from thrombocytopenia.

         17. Any other condition which, in the discretion of the investigator, would not allow safe
             participation in the study.

         18. Concomitant treatment with antiplatelet agents other than ASA.

         19. Recent malignancy or radiation therapy (=< 6 month).