Long-term, Open-label Follow-up Treatment of Patients With A-fib Who Have Been Previously Treated With BIBR 1048

Phase 2

Terminated

Conditions: Atrial Fibrillation
Stroke

Interventions: Drug: dabigatran etexilate

Registration Number: NCT00157248

Lead Sponsor: Boehringer Ingelheim

Brief Summary: To determine the long term safety and efficacy of BIBR 1048 in patients with chronic atrial fibrilla tion, with or without concomitant chronic treatment with acetylsalicylic acid (ASA).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 361

Inclusion Criteria

previous treatment with BIBR 1048 in PETRO (trial 1160.20- NCT01227629) and no premature discontinuation of therapy
paroxysmal, persistent, or permanent (chronic) non-rheumatic atrial fibrillation, documented by electrocardiogram (ECG) at least twice prior to enrollment in PETRO
concomitant coronary artery disease -an additional risk factor for stroke (one or more of the following conditions/events): hypertension, diabetes mellitus (DM), congestive heart failure (CHF) or Left ventricular dysfunction (LVD), previous ischemic stroke or transient ischemic attack) TIA, or age greater than 75 years. -age >= 18 years
written, informed consent

Exclusion criteria

Exclusion Criteria

Valvular heart disease conferring significantly increased risk of thromboembolic events (e.g. clinically significant mitral stenosis or prosthetic valves). planned cardioversion while patients are in the study.
contraindication to anticoagulant therapy (previous intracranial hemorrhage, gastro-intestinal (GI) hemorrhage within previous 3 months, previous severe hemorrhage with warfarin at therapeutic international normalized ratio (INR), regular use of non-steroidal anti-inflammatory drugs, hemorrhagic diathesis) major bleeding within the last 6 months (other than GI hemorrhage).
severe renal impairment (estimated glomerular filtration rate [GFR] <= 30 mL/min). uncontrolled hypertension (systolic blood pressure [SBP] > 180 mm Hg and/or diastolic blood pressure [DBP] > 100 mmHg).
Women who are pregnant or of childbearing potential who refuse to use a medically acceptable form of contraception throughout the study (note: a negative pregnancy test must be obtained for any woman of childbearing potential prior to entry into the study).
Patients who have received an investigational drug other than BIBR 1048 within the last 30 days.
Patients considered unreliable by the investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration. Another indication for anticoagulant treatment (eg, deep vein thrombosis or pulmonary embolus). Clinically significant anemia (note: patients with mild-moderate anemia should only be enrolled after the possibility of a GI bleeding source has been evaluated, the etiology of the anemia identified, and appropriate action taken). Patients suffering from thrombocytopenia (platelets < 100,000/uL). Any other condition which, in the discretion of the investigator, would not allow safe participation in the study.
Continuing or planned concomitant treatment with antiplatelet agents other than acetylsalicylic acid (ASA).
Recent malignancy or radiation therapy (<= 6 months).

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
dabigatran etexilate, 150 mg twice daily	dabigatran etexilate	dosage used at study start
dabigatran etexilate, 300 mg once daily	dabigatran etexilate	dosage used at study start
dabigatran etexilate, 150 mg once daily	dabigatran etexilate	dosage used at study start
dabigatran etexilate, 300 mg twice daily	dabigatran etexilate	dosage used at study start

Primary Outcome Measures

Name	Time	Method
Yearly Event Rate for Major + Minor/Relevant Bleeding	5 years	Time to first occurrence of either major or minor/relevant bleeding. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Major Bleeding	5 years	Time to first occurrence of fatal or life-threatening, retroperitoneal, intracranial, intraocular, or intraspinal bleeding, which required surgical treatment, led to a transfusion of a minimum of 2 units of packed cells or whole blood, or led to a fall in hemoglobin of 20g/L or less. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Composite Endpoint of Stroke, Transient Ischaemic Attacks, System Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and Mortality.	5 years	Time to first occurrence of stroke, transient ischaemic attacks, system thromboembolism, myocardial infarction, other major adverse cardiac events and mortality. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Any Bleeding	5 years	Time to first occurrence of any bleeding event. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Minor Bleeding	5 years	Time to first occurrence of minor bleeding. A minor bleeding event is any bleed that does not qualify as a major bleed. All minor bleeding events not fulfilling one of the criteria for clinically relevant were classified as nuisance bleeds. Clinically-relevant was defined as spontaneous skin hematoma ≥25 cm², spontaneous nose bleed \>5 min, macroscopic hematuria spontaneous or lasting longer than 24 hours if associated with an intervention, spontaneous rectal bleeding, gingival bleeding \>5 min, leading to hospitalization, leading to a transfusion of \<2 units of packed cells or whole blood and any other bleeding event considered clinically relevant by the investigator. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25

Secondary Outcome Measures

Name	Time	Method
Yearly Event Rate for Stroke	5 years	Time to first occurrence of any fatal or non-fatal stroke. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Ischaemic Stroke	5 years	Time to first occurrence of any ischaemic stroke. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Haemorrhagic Stroke	5 years	Time to first occurrence of any haemorrhagic stroke. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Transient Ischaemic Attacks	5 years	Time to first occurrence of any transient ischaemic attacks. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Systemic Thromboembolism	5 years	Time to first occurrence of any non-central nervous system systemic thromboembolism. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Myocardial Infarction	5 years	Time to first occurrence of any myocardial infarction. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Other Major Adverse Cardiac Events	5 years	Time to first occurrence of any other major adverse cardiac events. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate of Death	5 years	Time to death of any cause. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Yearly Event Rate for Composite Secondary Endpoint of Ischaemic Stroke, Transient Ischaemic Attacks, Non-central Nervous System Systemic Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and All-cause Mortality	5 years	Time to first occurrence of ischaemic stroke, transient ischaemic attacks, non-central nervous system systemic thromboembolism, myocardial infarction, other major adverse cardiac events and all-cause mortality. Yearly event rate (%) = number of subjects with event / subject-years \* 100. Subject years = sum (date of end of treatment - date of start of treatment) of all entered subjects / 365.25
Severe Adverse Event	5 years	Frequency of patients with severe adverse events.
Laboratory Analyses	5 years	Frequency of patients with possible clinically significant abnormalities, i.e. with values out of normal range. Normal ranges are defined as: * Alanine aminotransferase (ALT): 5-45 \[U/L\] * Aspartate aminotransferase (AST): 10-40 \[U/L\] * Bilirubin, total: 0.2-1.0 \[mg/dL\]

Trial Locations

Locations (50): 1160.42.10013 Boehringer Ingelheim Investigational Site
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New Hyde Park, New York, United States
1160.42.31008 Gelre Ziekenhuis, locatie Juliana
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Apeldoorn, Netherlands
1160.42.45005 Boehringer Ingelheim Investigational Site
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Aarhus C, Denmark
1160.42.10008 Boehringer Ingelheim Investigational Site
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Westminster, Maryland, United States
1160.42.10001 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1160.42.31001 Academisch Medisch Centrum
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Amsterdam, Netherlands
1160.42.31013 Onze Lieve Vrouwe Gasthuis
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Amsterdam, Netherlands
1160.42.10004 Boehringer Ingelheim Investigational Site
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Port Charlotte, Florida, United States
1160.42.10009 Boehringer Ingelheim Investigational Site
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North Durham, North Carolina, United States
1160.42.10002 Boehringer Ingelheim Investigational Site
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St. Petersburg, Florida, United States
1160.42.10015 Boehringer Ingelheim Investigational Site
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Baltimore, Maryland, United States
1160.42.10007 Boehringer Ingelheim Investigational Site
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Troy, Michigan, United States
1160.42.46013 Boehringer Ingelheim Investigational Site
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Eskilstuna, Sweden
1160.42.10003 Boehringer Ingelheim Investigational Site
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La Mesa, California, United States
1160.42.31003 Ziekenhuis Amstelveen
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Amstelveen, Netherlands
1160.42.10006 Boehringer Ingelheim Investigational Site
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Pensacola, Florida, United States
1160.42.10012 Boehringer Ingelheim Investigational Site
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Pittsfield, Massachusetts, United States
1160.42.10014 Boehringer Ingelheim Investigational Site
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Hawthorne, New York, United States
1160.42.46009 Boehringer Ingelheim Investigational Site
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Malmö, Sweden
1160.42.46006 Boehringer Ingelheim Investigational Site
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Umeaa, Sweden
1160.42.46005 Boehringer Ingelheim Investigational Site
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Jönköping, Sweden
1160.42.46008 Boehringer Ingelheim Investigational Site
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Norrköping, Sweden
1160.42.46007 Boehringer Ingelheim Investigational Site
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Falun, Sweden
1160.42.46004 Boehringer Ingelheim Investigational Site
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Örebro, Sweden
1160.42.46010 Boehringer Ingelheim Investigational Site
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Kalmar, Sweden
1160.42.46003 Boehringer Ingelheim Investigational Site
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Västerås, Sweden
1160.42.31006 Wilhelmina Ziekenhuis
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Assen, Netherlands
1160.42.31007 Gemini Ziekenhuis
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Den Helder, Netherlands
1160.42.31002 Ziekenhuis Gelderse Vallei
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Ede, Netherlands
1160.42.31014 Ziekenhuisgroep Twente
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Hengelo, Netherlands
1160.42.31012 Vasculair onderzoekscentrum (VOC)
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Hoorn, Netherlands
1160.42.31009 Havenziekenhuis
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Rotterdam, Netherlands
1160.42.31004 Maasland Ziekenhuis
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Sittard, Netherlands
1160.42.31005 Tweesteden Ziekenhuis
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Tilburg, Netherlands
1160.42.31011 Maxima Medisch Centrum
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Veldhoven, Netherlands
1160.42.45010 Boehringer Ingelheim Investigational Site
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Aalborg, Denmark
1160.42.45007 Boehringer Ingelheim Investigational Site
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Brædstrup, Denmark
1160.42.45011 Boehringer Ingelheim Investigational Site
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Esbjerg, Denmark
1160.42.45012 Boehringer Ingelheim Investigational Site
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Frederikssund, Denmark
1160.42.45003 Boehringer Ingelheim Investigational Site
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Helsingør, Denmark
1160.42.45004 Boehringer Ingelheim Investigational Site
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Herlev, Denmark
1160.42.45009 Boehringer Ingelheim Investigational Site
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Holbæk, Denmark
1160.42.45002 Boehringer Ingelheim Investigational Site
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Hvidovre, Denmark
1160.42.45014 Boehringer Ingelheim Investigational Site
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Køge, Denmark
1160.42.45001 Boehringer Ingelheim Investigational Site
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Odense, Denmark
1160.42.45013 Roskilde Sygehus
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Roskilde, Denmark
1160.42.45006 Boehringer Ingelheim Investigational Site
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Svendborg, Denmark
1160.42.46002 Boehringer Ingelheim Investigational Site
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Stockholm, Sweden
1160.42.46011 Boehringer Ingelheim Investigational Site
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Stockholm, Sweden
1160.42.46001 Boehringer Ingelheim Investigational Site
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Uppsala, Sweden