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

Atrial Fibrillation Clinical Trial

Official title:

Dose Exploration in Patients With Atrial Fibrillation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227629
• Other study ID #: 1160.20
• Secondary ID: PETRO trial
• Status: Completed
• Phase: Phase 2
• First received: October 22, 2010
• Last updated: April 22, 2014
• Start date: September 2003

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics CommitteeNetherlands: Medical Ethics Review Committee (METC)Sweden: Medical Products AgencyUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 502
• Est. primary completion date: November 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation

Intervention

Drug:
• dabigatran with ASA
dose comparison in combination
• dabigatran with ASA
dose comparison in combination
• dabigatran with ASA
dose comparison in combination
• dabigatran with ASA
dose comparison in combination
• dabigatran with ASA
dose comparison in combination
• dabigatran with ASA
dose comparison in combination
• warfarin
comparator
• dabigatran without ASA
dose comparison
• dabigatran without ASA
dose comparison
• dabigatran without ASA
dose comparison

Locations

Country	Name	City	State
Denmark	1160.20.45010	Aalborg
Denmark	1160.20.45005 Aarhus Sygehus	Aarhus C
Denmark	1160.20.45007 Medicinsk afdeling	Brædstrup
Denmark	1160.20.45011 Medicinsk afd.	Esbjerg
Denmark	1160.20.45012 Afdeling B3	Frederikssund
Denmark	1160.20.45003 Forskningscentret plan 3	Helsingør
Denmark	1160.20.45004 Herlev Hospital	Herlev
Denmark	1160.20.45009 Medicinsk amb. B8	Holbæk
Denmark	1160.20.45002 Kardiologisk afdeling	Hvidovre
Denmark	1160.20.45014 Hjertemedicinsk afd.	Køge
Denmark	1160.20.45001 Kardiologisk Laboratorium	Odense
Denmark	1160.20.45013 Kardiologisk afd.	Roskilde
Denmark	1160.20.45006 Medicinsk afdeling	Svendborg
Sweden	1160.20.46013 HIA, Mälarsjukhuset	Eskilstuna
Sweden	1160.20.46007 Falu Lasarett	Falun
Sweden	1160.20.46005 Ryhovs Länssjukhus	Jönköping
Sweden	1160.20.46010 Länssjukhuset Kalmar	Kalmar
Sweden	1160.20.46009 Universitetssjukhuset MAS	Malmö
Sweden	1160.20.46008 Vrinnevisjukhuset	Norrköping
Sweden	1160.20.46004 Universitetssjukhuset	Örebro
Sweden	1160.20.46002 Södersjukhuset	Stockholm
Sweden	1160.20.46011 Arytmienheten, Med klin	Stockholm
Sweden	1160.20.46006 Norrlands Universitetssjukhus	Umeå
Sweden	1160.20.46003 Centrallasarettet	Västerås
United States	1160.20.10015	Baltimore	Maryland
United States	1160.20.10010	Fayetteville	Arkansas
United States	1160.20.10005	Germantown	Tennessee
United States	1160.20.10014	Hawthorne	New York
United States	1160.20.10003 La Mesa Cardiac	La Mesa	California
United States	1160.20.10013	New Hyde Park	New York
United States	1160.20.10009	North Durham	North Carolina
United States	1160.20.10006 The Ford Research Institute, PA	Pensacola	Florida
United States	1160.20.10001	Philadelphia	Pennsylvania
United States	1160.20.10012	Pittsfield	Massachusetts
United States	1160.20.10004	Port Charlotte	Florida
United States	1160.20.10002	St. Petersburg	Florida
United States	1160.20.10007	Troy	Michigan
United States	1160.20.10008	Westminister	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Denmark,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Fatal or Life-threatening Major Bleeding Events	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	12 weeks	Yes
Primary	Number of Participants With Minor/Relevant Bleeding Events	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	12 weeks	Yes
Primary	Number of Participants With Minor/Nuisance Bleeding Events	All bleeding events not fulfilling one of the criteria for major bleeding event or minor/relevant bleeding events.	12 weeks	Yes
Secondary	Number of Participants With Thromboembolic Events: Composite Endpoint	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	12 weeks	No
Secondary	Number of Participants With Thromboembolic Events: Ischemic Stroke	Occurence of an ischemic stroke (fatal or non-fatal)	12 weeks	No
Secondary	Thromboembolic Events: Number of Participants With Transient Ischemic Attack	Occurence of a transient ischemic attack	12 weeks	No
Secondary	Thromboembolic Events: Number of Participants With Systemic Thromboembolism	Occurence of a systemic thromboembolism	12 weeks	No
Secondary	Thromboembolic Events: Number of Participants With Myocardial Infarction	Occurence of a myocardial infarction	12 weeks	No
Secondary	Thromboembolic Events: Number of Participants With Other Major Cardiac Events	Occurence of other major adverse cardiac events	12 weeks	No
Secondary	Thromboembolic Events: Number of Participants Who Died	Occurence of death by all causes	12 weeks	No
Secondary	D-dimer: Difference From Baseline	Difference in D-dimer from baseline to last available value	baseline and 12 weeks	No
Secondary	Soluble Fibrin: Difference From Baseline	Difference from baseline to visit 7	baseline and 12 weeks	No
Secondary	11-dehydrothromboxane B2 (TXB2): Difference From Baseline	Difference from baseline to visit 7	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)	The values of the trough plasma concentration of dabigatran (BIBR 953) are the by-patient geometric means of week 1, 4 and 12.	12 weeks	No
Secondary	Number of Participants With Increase of Aspartat-Aminotransferase (AST) to >2*Baseline	Increase of AST to more than two times the baseline value	12 weeks	Yes
Secondary	Number of Participants With Increase of Alkaline Phosphatase (AP) to >2*Baseline	Increase of AP to more than two times the baseline value	12 weeks	Yes
Secondary	Number of Participants With Increase of Bilirubin to >2*Baseline	Increase of Bilirubin to more than two times the baseline value	12 weeks	Yes
Secondary	Number of Participants With Increase of Alanine-Aminotransferase (ALT) to >2*Baseline	Number of Participants with Increase of ALT to more than two times the baseline value	12 weeks	Yes
Secondary	Severity of Adverse Events	Total number of patients with any adverse event of worst intensity 'mild', 'moderate' and 'severe'.	12 weeks	No

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