Atrial Fibrillation (AF) Patients Not Taking Vitamin-K Antagonist (VKA) - Full Text View

Purpose

The purpose of this study is to assess the safety and tolerability of AZD0837 in patients with atrial fibrillation who are unable or unwilling to take vitamin K antagonist therapy for up to 3 months.

Condition	Intervention	Phase
Persistent or Permanent Non-valvular Atrial Fibrillation	Drug: AZD0837 Drug: Aspirin	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	A Controlled, Randomized, Parallel , Multi-centre Feasibility Study of the Oral Direct Thrombin Inhibitor, AZD0837, Given as ER Formulation, in the Prevention of Stroke and Systolic Embolic Events in Patients With Atrial Fibrillation, Who Are Appropriate for But Unable/Unwilling to Take VKA Therapy

Resource links provided by NLM:

Genetics Home Reference related topics: familial atrial fibrillation

MedlinePlus related topics: Atrial Fibrillation Vitamin K

Drug Information available for: Aspirin

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Premature Discontinuation of Study or Study Drug Due to Any Reason [ Time Frame: 28 week (randomisation visit to last follow up visit in study) according to protocols ] [ Designated as safety issue: No ]
The premature discontinuation of study or study drug due to any reason
Premature Discontinuation of Study Drug Due to Any Reason [ Time Frame: 24 weeks (randomisation visit to last treatment visit) ] [ Designated as safety issue: No ]
The premature discontinuation of study drug due to any reason
Premature Discontinuation of Study Due to Any Reason [ Time Frame: 28 weeks (randomisation visit to last follow up visit) ] [ Designated as safety issue: No ]
/The premature discontinuation of study due to any reason
Compliance With Study Drug [ Time Frame: 24 weeks (randomisation visit to last treatment visit) according to protocol ] [ Designated as safety issue: No ]
[(number of doses dispensed-number of doses returned)/number of days between visits]*100
Compliance With Study Visits/Assessments [ Time Frame: 28 weeks (randomisation visit to last follow up visit) according to protocol ] [ Designated as safety issue: No ]
(number of visits attended acroos the time of study divided by the number of expected visits according to the time of entry into study)*100

Secondary Outcome Measures:

Bleeding Events [ Time Frame: 24 weeks (randomisation visit to last treatment visit) according to protocol. For patients who discontinued treatment the time frame was <24 weeks. Mean number of weeks was 7 weeks (baseline to end of treatment visit) ] [ Designated as safety issue: Yes ]
Number of patients with a bleeding event while on study drug. Patients with multiple bleeding events are counted once
Change in Creatinine Level [ Time Frame: 4 weeks according to protocol (randomisation visit to week 4 visit) ] [ Designated as safety issue: Yes ]
Individual change in Creatinine level (umil/L) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)
Alanine Aminotransferase (ALAT) [ Time Frame: 24 weeks (randomisation visit to last treatment visit) according to protocol. For patients who discontinued treatment the time frame was <24 weeks. Mean number of weeks was 7 weeks (baseline to end of treatment visit) ] [ Designated as safety issue: Yes ]
Number of patients while on study drug with Alanine aminotransferase (ALAT)>=3 times upper limit of normal.
Bilirubin [ Time Frame: 24 weeks (randomisation visit to last treatment visit) according to protocol. For patients who discontinued treatment the time frame was <24 weeks. Mean number of weeks was 7 weeks (baseline to end of treatment visit) ] [ Designated as safety issue: Yes ]
Number of patients while on study drug with Bilirubin>=2 times upper limit of normal.
Plasma Concentration of AZD0837 (Prodrug) [ Time Frame: 4 weeks after baseline according to protocol ] [ Designated as safety issue: Yes ]
Assessment of plasma concentration of AZD0837 (prodrug) made on the week 4 visit
Plasma Concentration of AR-H067637XX (Active Metabolite) [ Time Frame: 4 weeks after baseline according to protocol ] [ Designated as safety issue: Yes ]
Assessment of plasma concentration of AR-H067637XX (active metabolite) made on the week 4 visit
Change in D-Dimer Level [ Time Frame: 4 weeks according to protocol.(baseline to week 4 visit) ] [ Designated as safety issue: Yes ]
Individual change in D-Dimer level (ng/ml) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)
Activated Partial Thromboplastin Time (APTT) [ Time Frame: 4 weeks according to protocol.(baseline to week 4 visit) ] [ Designated as safety issue: Yes ]
Individual change in Activated partial thromboplastin time (APTT) (sec) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)
Ecarin Clotting Time (ECT) [ Time Frame: 4 weeks according to protocol.(baseline to week 4 visit) ] [ Designated as safety issue: No ]
Individual change in Ecarin clotting time (ECT) (sec) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)

Enrollment:	128
Study Start Date:	October 2007
Study Completion Date:	October 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Intervention Details:

ER formulation

Oral form

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Either one of the following risk factors is sufficient for inclusion (high risk patient)
Previous cerebral ischaemic attack (stroke or transient ischaemic attack (TIA), >30 days prior to randomization)
Previous systemic embolism or at least one of the following risk factors are needed for inclusion: Age ≥75 years
Symptomatic congestive heart failure
Impaired left ventricular systolic function
Diabetes mellitus; Hypertension requiring anti-hypertensive treatment
In addition to AF the patient must be appropriate for but unable or unwilling to take VKA therapy

Exclusion Criteria:

Presence of a clinically significant valvular heart disease;; Stroke or TIA and/or systemic embolism within the previous 30 days prior to randomization
Conditions associated with increased risk of major bleeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623779

Show 39 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator:

Gregory Y Lip, MD

Birmingham City Hospital

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00623779 History of Changes
Other Study ID Numbers:	D1250C00051
Study First Received:	February 15, 2008
Results First Received:	June 30, 2011
Last Updated:	March 20, 2012
Health Authority:	Denmark: Danish Medicines Agency Norway: Norwegian Medicines Agency Poland: Ministry of Health Russia: Ministry of Health of the Russian Federation Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:

Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Aspirin
Antithrombins
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents

Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants

ClinicalTrials.gov processed this record on May 19, 2013