Clinical trial NCT00684307: Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
Official title: A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonvalvular Atrial Fibrillation
Keywords: Anticoagulant Treatment
Risk Factors For Stroke
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2008-05-26
Enrollment: 1084
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 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.


Eligibility criteria: 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.

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

Primary outcomes:
measure: Bleeding Events
timeFrame: 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)
measure: Creatinine
timeFrame: 12 weeks according to protocol.(baseline to week 12 visit)
measure: Alanine Aminotransferase (ALAT)
timeFrame: 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)
measure: Bilirubin
timeFrame: 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)
Secondary outcomes:
measure: D-Dimer
timeFrame: 14 weeks according to protocol.(enrolment to week 12 visit)
measure: Activated Partial Thromboplastin Time (APTT)
timeFrame: 12 weeks according to protocol.(baseline to week 12 visit)
measure: Ecarin Clotting Time (ECT)
timeFrame: 12 weeks according to protocol.(baseline to week 12 visit)
measure: Plasma Concentration of AZD0837 (Prodrug)
timeFrame: 12 weeks after baseline according to protocol
measure: Plasma Concentration of AR-H067637XX (Active Metabolite)
timeFrame: 12 weeks after baseline according to protocol
measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT
timeFrame: 36 weeks according to protocol
measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC
timeFrame: 36 weeks according to protocol
measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC
timeFrame: 36 weeks according to protocol
Other outcomes:
Locations:
Study officials:
affiliation: University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK
name: Gregory Y Lip, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U, Wahlander KF; Steering Committee. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J. 2009 Dec;30(23):2897-907. doi: 10.1093/eurheartj/ehp318. Epub 2009 Aug 18.