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

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ClinicalTrials.gov Identifier: NCT00684307
Recruitment Status : Completed
First Posted : May 26, 2008
Results First Posted : September 22, 2011
Last Update Posted : March 23, 2012
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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.

Condition or disease Intervention/treatment Phase
Nonvalvular Atrial Fibrillation Drug: AZD0837 Drug: Vitamin-K antagonist at INR 2-3 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1084 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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 Start Date : February 2007
Actual Primary Completion Date : June 2008
Actual Study Completion Date : June 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Warfarin

Arms and Interventions
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Arm Intervention/treatment
Experimental: 1
AZD0837 450 mg
 Drug: AZD0837
ER tablet, PO, once daily for a period of 3-9 months.
Experimental: 2
AZD0837 200 mg
 Drug: AZD0837
ER tablet, PO, twice daily for a period of 3-9 months
Experimental: 3
AZD0837 300 mg
 Drug: AZD0837
ER tablet, PO, once daily for a period of 3-9 months.
Experimental: 4
AZD0837 150 mg
 Drug: AZD0837
ER tablet, PO, once daily for a period of 3-9 months.
Active Comparator: 5
Vitamin-K antagonist at INR 2-3
 Drug: Vitamin-K antagonist at INR 2-3
Tablet, PO for a period of 3-9 months.
Other Name: Warfarin


Outcome Measures
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Primary Outcome Measures :
  1. Bleeding Events [ Time Frame: 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

  2. Creatinine [ Time Frame: 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)

  3. Alanine Aminotransferase (ALAT) [ Time Frame: 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

  4. Bilirubin [ Time Frame: 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 :
  1. D-Dimer [ Time Frame: 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)

  2. Activated Partial Thromboplastin Time (APTT) [ Time Frame: 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)

  3. Ecarin Clotting Time (ECT) [ Time Frame: 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)

  4. Plasma Concentration of AZD0837 (Prodrug) [ Time Frame: 12 weeks after baseline according to protocol ]
    Assessment made on the week 12 visit

  5. Plasma Concentration of AR-H067637XX (Active Metabolite) [ Time Frame: 12 weeks after baseline according to protocol ]
    Assessment made on the week 12 visit

  6. Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT [ Time Frame: 36 weeks according to protocol ]
    Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T

  7. Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC [ Time Frame: 36 weeks according to protocol ]
    Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T

  8. Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC [ Time Frame: 36 weeks according to protocol ]
    Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00684307


Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Gregory Y Lip, Prof University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00684307    
Other Study ID Numbers: D1250C00008
First Posted: May 26, 2008    Key Record Dates
Results First Posted: September 22, 2011
Last Update Posted: March 23, 2012
Last Verified: March 2012
Keywords provided by AstraZeneca:
Anticoagulant Treatment
Risk Factors For Stroke
Additional relevant MeSH terms:
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Atrial Fibrillation
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes
Vitamin K
Warfarin
Vitamins
Micronutrients
 Nutrients
Growth Substances
Physiological Effects of Drugs
Anticoagulants
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants