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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01227629
First received: October 22, 2010
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Drug: dabigatran with ASA
Drug: warfarin
Drug: dabigatran without ASA
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Prevention
Official Title: Dose Exploration in Patients With Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Number of Participants With Fatal or Life-threatening Major Bleeding Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Retroperitoneal, intracranial, intraocular, or intraspinal bleeding, or requiring surgical treatment, or leading to a transfusion of 2 units or more, or leading to a fall in hemoglobin of 20g/L or more

  • Number of Participants With Minor/Relevant Bleeding Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Haematuria, rectal bleeding, gingival bleeding, skin hematoma of 25cm^2 or more, nose bleed of more than 5 minutes duration, bleeding leading to a hospitalization, leading to a transfusion of less than 2 units or any other clinically relevant bleeding

  • Number of Participants With Minor/Nuisance Bleeding Events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    All bleeding events not fulfilling one of the criteria for major bleeding event or minor/relevant bleeding events.


Secondary Outcome Measures:
  • Number of Participants With Thromboembolic Events: Composite Endpoint [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Combination of ischemic stroke (fatal or non fatal), transient ischemic attack, systemic thromboembolism, myocardial infarction (fatal or non fatal), other major adverse cardiac event and all cause mortality

  • Number of Participants With Thromboembolic Events: Ischemic Stroke [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Occurence of an ischemic stroke (fatal or non-fatal)

  • Thromboembolic Events: Number of Participants With Transient Ischemic Attack [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Occurence of a transient ischemic attack

  • Thromboembolic Events: Number of Participants With Systemic Thromboembolism [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Occurence of a systemic thromboembolism

  • Thromboembolic Events: Number of Participants With Myocardial Infarction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Occurence of a myocardial infarction

  • Thromboembolic Events: Number of Participants With Other Major Cardiac Events [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Occurence of other major adverse cardiac events

  • Thromboembolic Events: Number of Participants Who Died [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Occurence of death by all causes

  • D-dimer: Difference From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Difference in D-dimer from baseline to last available value

  • Soluble Fibrin: Difference From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Difference from baseline to visit 7

  • 11-dehydrothromboxane B2 (TXB2): Difference From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
    Difference from baseline to visit 7

  • Ecarin Clotting Time (ECT): Difference From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Activated Partial Thromboplastin Time (aPTT): Difference From Baseline [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  • Trough Plasma Concentration of Dabigatran (BIBR 953) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The values of the trough plasma concentration of dabigatran (BIBR 953) are the by-patient geometric means of week 1, 4 and 12.

  • Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Increase of AST to more than two times the baseline value

  • Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Increase of AP to more than two times the baseline value

  • Number of Participants With Increase of Bilirubin to >2*Baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Increase of Bilirubin to more than two times the baseline value

  • Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Number of Participants with Increase of ALT to more than two times the baseline value

  • Severity of Adverse Events [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Total number of patients with any adverse event of worst intensity 'mild', 'moderate' and 'severe'.


Enrollment: 502
Study Start Date: September 2003
Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dabigatran 50 mg twice daily (bid)
Dabigatran: one capsule in the morning and 1 capsule in the evening. Twice daily (bis in die = bid).
Drug: dabigatran without ASA
dose comparison
Experimental: dabigatran 50 mg bid + 81 mg ASA qd
Dabigatran: one capsule in the morning and 1 capsule in the evening. Acetylsalicylic acid (ASA) once daily (quaque dies = qd) in the morning.
Drug: dabigatran with ASA
dose comparison in combination
Experimental: dabigatran 50 mg bid + 325 mg ASA qd
Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
Drug: dabigatran with ASA
dose comparison in combination
Experimental: dabigatran 150 mg bid
Dabigatran: one capsule in the morning and 1 capsule in the evening
Drug: dabigatran without ASA
dose comparison
Experimental: dabigatran 150 mg bid + 81 mg ASA qd
Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
Drug: dabigatran with ASA
dose comparison in combination
Experimental: dabigatran 150 mg bid + 325 mg ASA qd
Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
Drug: dabigatran with ASA
dose comparison in combination
Experimental: dabigatran 300 mg bid
Dabigatran: one capsule in the morning and 1 capsule in the evening
Drug: dabigatran without ASA
dose comparison
Experimental: dabigatran 300 mg bid + 81 mg ASA qd
Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
Drug: dabigatran with ASA
dose comparison in combination
Experimental: dabigatran 300 mg bid + 325 mg ASA qd
Dabigatran: one capsule in the morning and 1 capsule in the evening. ASA in the morning
Drug: dabigatran with ASA
dose comparison in combination
Active Comparator: warfarin
once daily, dosed to target International Normalised Ratio (INR) 2.0 to 3.0
Drug: warfarin
comparator

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227629

  Show 38 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01227629     History of Changes
Other Study ID Numbers: 1160.20, PETRO trial
Study First Received: October 22, 2010
Results First Received: November 18, 2010
Last Updated: April 22, 2014
Health Authority: Denmark: Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)
Sweden: Medical Products Agency
United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Dabigatran
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014