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Phase 2 N=949 Randomized Triple-blind Prevention

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

Nonvalvular Atrial Fibrillation

Enrolled (actual)
949
Serious AEs
14.7%
Results posted
Sep 2011
Primary outcome: Primary: Bleeding Events — 18; 8; 22; 17 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
AZD0837 (Drug); Vitamin-K antagonist at INR 2-3 (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
AstraZeneca
Primary completion
Jun 2008

Outcome Measures

OutcomeResultp-value
PRIMARY
Bleeding Events
18; 8; 22; 17; 46
PRIMARY
Creatinine
5.95; 4.81; 7.56; 9.22; 0.43
PRIMARY
Alanine Aminotransferase (ALAT)
6; 1; 5; 2; 5
PRIMARY
Bilirubin
1; 0; 0; 3; 2
SECONDARY
D-Dimer
-46.4; -76.9; -45.2; -68.0; -50.3
SECONDARY
Activated Partial Thromboplastin Time (APTT)
8.2; 12.3; 17.4; 16.4
SECONDARY
Ecarin Clotting Time (ECT)
33.5; 53.0; 64.0; 73.5
SECONDARY
Plasma Concentration of AZD0837 (Prodrug)
199.8; 617.5; 564.5; 1143.5
SECONDARY
Plasma Concentration of AR-H067637XX (Active Metabolite)
223.8; 373.6; 454.8; 600.8
SECONDARY
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT
39.7; 42.4; 36.3; 35.6
SECONDARY
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC
39.2; 39.3; 37.7; 40
SECONDARY
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC
40.9; 41.1; 43.4; 39.6

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00684307). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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