Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation

Phase 2

Completed

• Conditions: Nonvalvular Atrial Fibrillation
• Interventions: Drug: AZD0837; Drug: Vitamin-K antagonist at INR 2-3

• Registration Number: NCT00684307
• Lead Sponsor: AstraZeneca

Brief Summary

The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02
• Study First Submitted: 2008-05-22
• Study First Submitted QC: 2008-05-23
• Study First Posted: 2008-05-26
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Results First Submitted: 2011-08-17
• Results First Submitted QC: 2011-08-17
• Results First Posted: 2011-09-22
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-20
• Last Update Posted: 2012-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1084

Inclusion Criteria

• Nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week.
• Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
• Previous systemic embolism.
• Symptomatic congestive heart failure (CHF)
• Impaired left ventricular systolic function
• Diabetes mellitus
• Hypertension requiring anti-hypertensive treatment.

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Exclusion Criteria

• AF secondary to reversible disorders, eg hyperthyroidism, drugs and pulmonary embolism
• Known contraindication to VKA treatment
• Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than AF requiring chronic anticoagulation treatment
• Conditions associated with increased risk of major bleeding for example: history of intracranial bleeding, history of bleeding gastrointestinal disorder or major surgical procedure or trauma two weeks prior to randomization

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	AZD0837	AZD0837 450 mg
2	AZD0837	AZD0837 200 mg
3	AZD0837	AZD0837 300 mg
4	AZD0837	AZD0837 150 mg
5	Vitamin-K antagonist at INR 2-3	Vitamin-K antagonist at INR 2-3

Primary Outcome Measures

Name	Time	Method
Creatinine	12 weeks according to protocol.(baseline to week 12 visit)	Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Bleeding Events	36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)	Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once
Alanine Aminotransferase (ALAT)	36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)	Number of patients while on study drug with ALAT\>=3 times upper limit of normal.l
Bilirubin	36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)	Number of patients while on study drug with Bilirubin\>=2 times upper limit of normal

Secondary Outcome Measures

Name	Time	Method
Ecarin Clotting Time (ECT)	12 weeks according to protocol.(baseline to week 12 visit)	Change in Ecarin clotting time (ECT) from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Plasma Concentration of AZD0837 (Prodrug)	12 weeks after baseline according to protocol	Assessment made on the week 12 visit
Plasma Concentration of AR-H067637XX (Active Metabolite)	12 weeks after baseline according to protocol	Assessment made on the week 12 visit
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT	36 weeks according to protocol	Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T
D-Dimer	14 weeks according to protocol.(enrolment to week 12 visit)	Change in D-Dimer values from enrolment to week 12 visit for VKA naïve patients while on study drug (week 12 visit-enrolment)
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC	36 weeks according to protocol	Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC	36 weeks according to protocol	Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T
Activated Partial Thromboplastin Time (APTT)	12 weeks according to protocol.(baseline to week 12 visit)	Change in Activated partial thromboplastin time (APTT) from baseline to week 12 visit for VKA naïve patients while on study drug (week 12 visit-baseline)