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

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:

Genetics Home Reference related topics: familial atrial fibrillation

MedlinePlus related topics: Atrial Fibrillation Blood Thinners

Drug Information available for: Warfarin Warfarin sodium Dabigatran Dabigatran etexilate Dabigatran etexilate mesylate

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

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, introcular, 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 ]
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 time 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 time 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 time 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

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

Non-rheumatic atrial fibrillation.
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.
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)
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.
Age > = 18 years at entry.
Written, informed consent.

Exclusion criteria

Valvular heart disease.
Planned cardioversion.
Recent (=< 1 month) myocardial infarction, stroke or transient ischemic attack (TIA), or patients who have received a coronary stent within the last 6 months.
Intolerance or contraindications to acetylsalicylic acid (ASA).
Any contraindication to anticoagulant therapy.
Major bleeding within the last 6 months (other than gastrointestinal (GI) hemorrhage).
Severe renal impairment (estimated glomerular filtration rate (GFR) =< 30 mL/min).
Uncontrolled hypertension (SBP > 180 mmHg and/or DBP > 100 mmHg).
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.
Women who are pregnant or of childbearing potential who refuses to use a medically acceptable form of contraception throughout the study.
Patients who have received an investigational drug within the last 30 days.
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.
Patients considered unreliable by the investigator.
Another indication for anticoagulant treatment.
Patients suffering from anemia.
Patients suffering from thrombocytopenia.
Any other condition which, in the discretion of the investigator, would not allow safe participation in the study.
Concomitant treatment with antiplatelet agents other than ASA.
Recent malignancy or radiation therapy (=< 6 month).

Contacts and Locations

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

Show 38 Study Locations

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

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:	May 23, 2012
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

Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013