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

Nonvalvular Atrial Fibrillation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00684307
• Other study ID #: D1250C00008
• Status: Completed
• Phase: Phase 2
• First received: May 22, 2008
• Last updated: March 20, 2012
• Start date: February 2007
• Est. completion date: June 2008

Study information

• Verified date: March 2012
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyDenmark: Danish Medicines AgencyHungary: National Institute of PharmacyIreland: Irish Medicines BoardNorway: Norwegian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of Health of the Russian FederationSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1084
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Atrial Fibrillation
• Nonvalvular Atrial Fibrillation

Intervention

Drug:
• AZD0837
ER tablet, PO, once daily for a period of 3-9 months.
• Vitamin-K antagonist at INR 2-3
Tablet, PO for a period of 3-9 months.
• AZD0837
ER tablet, PO, twice daily for a period of 3-9 months

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bleeding Events	Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once	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)	Yes
Primary	Creatinine	Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)	12 weeks according to protocol.(baseline to week 12 visit)	Yes
Primary	Alanine Aminotransferase (ALAT)	Number of patients while on study drug with ALAT>=3 times upper limit of normal.l	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)	Yes
Primary	Bilirubin	Number of patients while on study drug with Bilirubin>=2 times upper limit of normal	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)	Yes
Secondary	D-Dimer	Change in D-Dimer values from enrolment to week 12 visit for VKA naïve patients while on study drug (week 12 visit-enrolment)	14 weeks according to protocol.(enrolment to week 12 visit)	Yes
Secondary	Activated Partial Thromboplastin Time (APTT)	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)	12 weeks according to protocol.(baseline to week 12 visit)	Yes
Secondary	Ecarin Clotting Time (ECT)	Change in Ecarin clotting time (ECT) from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)	12 weeks according to protocol.(baseline to week 12 visit)	Yes
Secondary	Plasma Concentration of AZD0837 (Prodrug)	Assessment made on the week 12 visit	12 weeks after baseline according to protocol	No
Secondary	Plasma Concentration of AR-H067637XX (Active Metabolite)	Assessment made on the week 12 visit	12 weeks after baseline according to protocol	No
Secondary	Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT	Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T	36 weeks according to protocol	No
Secondary	Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC	Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T	36 weeks according to protocol	No
Secondary	Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC	Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T	36 weeks according to protocol	No