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

Stroke Clinical Trial

Official title:

Long-term, Open-label Follow-up Treatment of Patients With Atrial Fibrillation Who Have Been Previously Treated With BIBR 1048 in the PETRO Trial (Trial 1160.20 - NCT01227629). (PETRO Extension Trial: PETRO-Ex)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00157248
• Other study ID #: 1160.42
• Status: Terminated
• Phase: Phase 2
• First received: September 8, 2005
• Last updated: May 8, 2014
• Start date: December 2003

Study information

• Verified date: February 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Sweden: Medical Products AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 361
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria Diagnosis and main criteria for inclusion: Paroxysmal, persistent, or permanent (chronic) non-rheumatic atrial fibrillation with a history of coronary artery disease (CAD)

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation
• Stroke

Intervention

Drug:
• dabigatran etexilate
dosage used at study start
• dabigatran etexilate
dosage used at study start
• dabigatran etexilate
dosage used at study start
• dabigatran etexilate
dosage used at study start

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Denmark,  Netherlands,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Yearly Event Rate for Composite Endpoint of Stroke, Transient Ischaemic Attacks, System Thromboembolism, Myocardial Infarction, Other Major Adverse Cardiac Events and Mortality.	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	5 years	No
Primary	Yearly Event Rate for Major Bleeding	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	5 years	Yes
Primary	Yearly Event Rate for Major + Minor/Relevant Bleeding	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	5 years	Yes
Primary	Yearly Event Rate for Any Bleeding	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	5 years	Yes
Primary	Yearly Event Rate for Minor Bleeding	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	5 years	Yes
Secondary	Yearly Event Rate for Stroke	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	5 years	No
Secondary	Yearly Event Rate of Ischaemic Stroke	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	5 years	No
Secondary	Yearly Event Rate of Haemorrhagic Stroke	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	5 years	Yes
Secondary	Yearly Event Rate for Transient Ischaemic Attacks	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	5 years	No
Secondary	Yearly Event Rate for Systemic Thromboembolism	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	5 years	No
Secondary	Yearly Event Rate of Myocardial Infarction	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	5 years	No
Secondary	Yearly Event Rate of Other Major Adverse Cardiac Events	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	5 years	No
Secondary	Yearly Event Rate of Death	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	5 years	No
Secondary	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	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	5 years	No
Secondary	Severe Adverse Event	Frequency of patients with severe adverse events.	5 years	No
Secondary	Laboratory Analyses	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]	5 years	No

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