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

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

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.

Study Overview

• Status: Completed
• Conditions: Persistent or Permanent Non-valvular Atrial Fibrillation
• Intervention / Treatment: Drug: AZD0837; Drug: Aspirin

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Research Site
  • Arhus N, Denmark
    • Research Site
  • Copenhagen, Denmark
    • Research Site
  • Esbjerg, Denmark
    • Research Site
  • Frederikssund, Denmark
    • Research Site
  • Horsens, Denmark
    • Research Site
  • Kobenhavn, Denmark
    • Research Site
  • Silkeborg, Denmark
    • Research Site
  • Svendborg, Denmark
    • Research Site
• Norway
  • Elverum, Norway
    • Research Site
  • Gjettum, Norway
    • Research Site
  • Kongsberg, Norway
    • Research Site
  • Oslo, Norway
    • Research Site
  • Stovner, Norway
    • Research Site
  • Straume, Norway
    • Research Site
• Poland
  • Bytom, Poland
    • Research Site
  • Czestochowa, Poland
    • Research Site
  • Krakow, Poland
    • Research Site
  • Lodz, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Ostrow Mazowiecka, Poland
    • Research Site
  • Otwock, Poland
    • Research Site
  • Plock, Poland
    • Research Site
  • Ruda Slaska, Poland
    • Research Site
  • Sopot, Poland
    • Research Site
  • Torun, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
• Russian Federation
  • Moscow, Russian Federation
    • Research Site
  • St. Petersburg, Russian Federation
    • Research Site
• Sweden
  • Boras, Sweden
    • Research Site
  • Goteborg, Sweden
    • Research Site
  • Lund, Sweden
    • Research Site
  • Malmo, Sweden
    • Research Site
  • Molndal, Sweden
    • Research Site
  • Stockholm, Sweden
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom
    • Research Site
  • Eastbourne, United Kingdom
    • Research Site
  • Newcastle Upon Tyne, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Premature Discontinuation of Study or Study Drug Due to Any Reason	The premature discontinuation of study or study drug due to any reason	28 week (randomisation visit to last follow up visit in study) according to protocols
Premature Discontinuation of Study Drug Due to Any Reason	The premature discontinuation of study drug due to any reason	24 weeks (randomisation visit to last treatment visit)
Premature Discontinuation of Study Due to Any Reason	|The premature discontinuation of study due to any reason	28 weeks (randomisation visit to last follow up visit)
Compliance With Study Drug	[(number of doses dispensed-number of doses returned)/number of days between visits]*100	24 weeks (randomisation visit to last treatment visit) according to protocol
Compliance With Study Visits/Assessments	(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	28 weeks (randomisation visit to last follow up visit) according to protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding Events	Number of patients with a bleeding event while on study drug. Patients with multiple bleeding events are counted once	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)
Change in Creatinine Level	Individual change in Creatinine level (umil/L) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)	4 weeks according to protocol (randomisation visit to week 4 visit)
Alanine Aminotransferase (ALAT)	Number of patients while on study drug with Alanine aminotransferase (ALAT)>=3 times upper limit of normal.	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)
Bilirubin	Number of patients while on study drug with Bilirubin>=2 times upper limit of normal.	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)
Plasma Concentration of AZD0837 (Prodrug)	Assessment of plasma concentration of AZD0837 (prodrug) made on the week 4 visit	4 weeks after baseline according to protocol
Plasma Concentration of AR-H067637XX (Active Metabolite)	Assessment of plasma concentration of AR-H067637XX (active metabolite) made on the week 4 visit	4 weeks after baseline according to protocol
Change in D-Dimer Level	Individual change in D-Dimer level (ng/ml) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)	4 weeks according to protocol.(baseline to week 4 visit)
Activated Partial Thromboplastin Time (APTT)	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)	4 weeks according to protocol.(baseline to week 4 visit)
Ecarin Clotting Time (ECT)	Individual change in Ecarin clotting time (ECT) (sec) from baseline to week 4 visit for patients while on study drug (week 4 visit-baseline)	4 weeks according to protocol.(baseline to week 4 visit)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Gregory Y Lip, MD, Birmingham City Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: February 15, 2008
• First Submitted That Met QC Criteria: February 15, 2008
• First Posted (Estimate): February 26, 2008

Study Record Updates

• Last Update Posted (Estimate): March 23, 2012
• Last Update Submitted That Met QC Criteria: March 20, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: D1250C00051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No