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Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
This study has been completed.
Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00684307
First received: May 22, 2008
Last updated: March 20, 2012
Last verified: March 2012
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Purpose
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 | Intervention | Phase |
|---|---|---|
| Nonvalvular Atrial Fibrillation | Drug: AZD0837 Drug: Vitamin-K antagonist at INR 2-3 | Phase 2 |
| Study Type: | Interventional |
| Study Design: | 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 |
Resource links provided by NLM:
Further study details as provided by AstraZeneca:
Primary Outcome Measures:
- 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
- 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)
- 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
- 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:
- 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)
- 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)
- 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)
- Plasma Concentration of AZD0837 (Prodrug) [ Time Frame: 12 weeks after baseline according to protocol ]Assessment made on the week 12 visit
- Plasma Concentration of AR-H067637XX (Active Metabolite) [ Time Frame: 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 [ Time Frame: 36 weeks according to protocol ]Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T
- 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
- 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
| Enrollment: | 1084 |
| Study Start Date: | February 2007 |
| Study Completion Date: | June 2008 |
| Primary Completion Date: | June 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
|
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00684307
Please refer to this study by its ClinicalTrials.gov identifier: NCT00684307
Sponsors and Collaborators
AstraZeneca
Investigators
| Principal Investigator: | Gregory Y Lip, Prof | University Department of Medicine, City Hospital, Birmingham, B18 7QH, England, UK |
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT00684307 History of Changes |
| Other Study ID Numbers: |
D1250C00008 |
| Study First Received: | May 22, 2008 |
| Results First Received: | August 17, 2011 |
| Last Updated: | March 20, 2012 |
Keywords provided by AstraZeneca:
|
Anticoagulant Treatment Risk Factors For Stroke |
Additional relevant MeSH terms:
|
Atrial Fibrillation Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Vitamins Vitamin K Micronutrients |
Growth Substances Physiological Effects of Drugs Antifibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Hemostatics Coagulants |
ClinicalTrials.gov processed this record on August 17, 2017