Clinical trial NCT01227629: PETRO Stroke Prevention in Patients With AF by Treatment With Dabigatran, With and Without Aspirin, Compared to Warfarin
Official title: Dose Exploration in Patients With Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).

Primary outcomes:
measure: Number of Participants With Fatal or Life-threatening Major Bleeding Events
timeFrame: 12 weeks
measure: Number of Participants With Minor/Relevant Bleeding Events
timeFrame: 12 weeks
measure: Number of Participants With Minor/Nuisance Bleeding Events
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Participants With Thromboembolic Events: Composite Endpoint
timeFrame: 12 weeks
measure: Number of Participants With Thromboembolic Events: Ischemic Stroke
timeFrame: 12 weeks
measure: Thromboembolic Events: Number of Participants With Transient Ischemic Attack
timeFrame: 12 weeks
measure: Thromboembolic Events: Number of Participants With Systemic Thromboembolism
timeFrame: 12 weeks
measure: Thromboembolic Events: Number of Participants With Myocardial Infarction
timeFrame: 12 weeks
measure: Thromboembolic Events: Number of Participants With Other Major Cardiac Events
timeFrame: 12 weeks
measure: Thromboembolic Events: Number of Participants Who Died
timeFrame: 12 weeks
measure: D-dimer: Difference From Baseline
timeFrame: baseline and 12 weeks
measure: Soluble Fibrin: Difference From Baseline
timeFrame: baseline and 12 weeks
measure: 11-dehydrothromboxane B2 (TXB2): Difference From Baseline
timeFrame: baseline and 12 weeks
measure: Ecarin Clotting Time (ECT): Difference From Baseline
timeFrame: baseline and 12 weeks
measure: Activated Partial Thromboplastin Time (aPTT): Difference From Baseline
timeFrame: baseline and 12 weeks
measure: Trough Plasma Concentration of Dabigatran (BIBR 953)
timeFrame: 12 weeks
measure: Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline
timeFrame: 12 weeks
measure: Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline
timeFrame: 12 weeks
measure: Number of Participants With Increase of Bilirubin to >2*Baseline
timeFrame: 12 weeks
measure: Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline
timeFrame: 12 weeks
measure: Severity of Adverse Events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: 1160.20.10010
state: Arkansas
city: La Mesa
country: United States
facility: 1160.20.10003 La Mesa Cardiac
state: California
city: Pensacola
country: United States
facility: 1160.20.10006 The Ford Research Institute, PA
state: Florida
city: Port Charlotte
country: United States
facility: 1160.20.10004
state: Florida
city: St. Petersburg
country: United States
facility: 1160.20.10002
state: Florida
city: Baltimore
country: United States
facility: 1160.20.10015
state: Maryland
city: Westminister
country: United States
facility: 1160.20.10008
state: Maryland
city: Pittsfield
country: United States
facility: 1160.20.10012
state: Massachusetts
city: Troy
country: United States
facility: 1160.20.10007
state: Michigan
city: Hawthorne
country: United States
facility: 1160.20.10014
state: New York
city: New Hyde Park
country: United States
facility: 1160.20.10013
state: New York
city: North Durham
country: United States
facility: 1160.20.10009
state: North Carolina
city: Philadelphia
country: United States
facility: 1160.20.10001
state: Pennsylvania
city: Germantown
country: United States
facility: 1160.20.10005
state: Tennessee
city: Aalborg
country: Denmark
facility: 1160.20.45010
city: Aarhus C
country: Denmark
facility: 1160.20.45005 Aarhus Sygehus
city: Brædstrup
country: Denmark
facility: 1160.20.45007 Medicinsk afdeling
city: Esbjerg
country: Denmark
facility: 1160.20.45011 Medicinsk afd.
city: Frederikssund
country: Denmark
facility: 1160.20.45012 Afdeling B3
city: Helsingør
country: Denmark
facility: 1160.20.45003 Forskningscentret plan 3
city: Herlev
country: Denmark
facility: 1160.20.45004 Herlev Hospital
city: Holbæk
country: Denmark
facility: 1160.20.45009 Medicinsk amb. B8
city: Hvidovre
country: Denmark
facility: 1160.20.45002 Kardiologisk afdeling
city: Køge
country: Denmark
facility: 1160.20.45014 Hjertemedicinsk afd.
city: Odense
country: Denmark
facility: 1160.20.45001 Kardiologisk Laboratorium
city: Roskilde
country: Denmark
facility: 1160.20.45013 Kardiologisk afd.
city: Svendborg
country: Denmark
facility: 1160.20.45006 Medicinsk afdeling
city: Eskilstuna
country: Sweden
facility: 1160.20.46013 HIA, Mälarsjukhuset
city: Falun
country: Sweden
facility: 1160.20.46007 Falu Lasarett
city: Jönköping
country: Sweden
facility: 1160.20.46005 Ryhovs Länssjukhus
city: Kalmar
country: Sweden
facility: 1160.20.46010 Länssjukhuset Kalmar
city: Malmö
country: Sweden
facility: 1160.20.46009 Universitetssjukhuset MAS
city: Norrköping
country: Sweden
facility: 1160.20.46008 Vrinnevisjukhuset
city: Stockholm
country: Sweden
facility: 1160.20.46002 Södersjukhuset
city: Stockholm
country: Sweden
facility: 1160.20.46011 Arytmienheten, Med klin
city: Umeå
country: Sweden
facility: 1160.20.46006 Norrlands Universitetssjukhus
city: Västerås
country: Sweden
facility: 1160.20.46003 Centrallasarettet
city: Örebro
country: Sweden
facility: 1160.20.46004 Universitetssjukhuset
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: