Long-term Safety in Atrial Fibrillation Patients

Long-term Treatment With the Oral Direct Thrombin Inhibitor AZD0837, Compared to Vitamin-K Antagonists, as Stroke Prevention in Patients With Non-valvular Atrial Fibrillation and One or More Risk Factors for Stroke and Systemic Embolic Events. A 5-year Follow-up Study

The purpose of this study is to provide safety and tolerability data for AZD0837 during long-term treatment (5 years) in patients with non-valvular atrial fibrillation (AF) and one or more additional risk factors for stroke and systemic embolic events (moderate to high risk patients).

Study Overview

• Status: Completed
• Conditions: Persistent or Permanent Nonvalvular Atrial Fibrillation
• Intervention / Treatment: Drug: AZD0837; Drug: VKA INR 2-3

• Study Type: Interventional
• Enrollment (Actual): 523
• Phase: Phase 2

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:

• Patients with paroxysmal, persistent or permanent Non Valvular Atrial Fibrillation with one or more additional risk factors for stroke and systemic embolic event
• completing treatment with study drug in D1250C00008.

Exclusion Criteria:

• Atrial Fibrillation secondary to reversible disorders, eg hyperthyroidism
• Presence of a valvular heart disease, mechanical heart valves, active endocarditis, left ventricular aneurysm or thrombus, atrial myxoma or any condition other than Atrial Fibrillation requiring chronic anticoagulation treatment
• Myocardial infarction, heart surgery or percutaneous coronary intervention (PCI) within the previous three months prior to inclusion; Stroke and/or systemic embolism within the previous 30 days prior to inclusion
• Conditions associated with increased risk of major bleeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: AZD0837; Treatment with AZD0837 starting with 4 different doses, 150 mg od, 300 mg od, 200 mg bid or 450 mg od and then switching to one general common dose, 300 mg od
Active Comparator: 2	Drug: VKA INR 2-3; Vitamin K antagonists (VKA), titrated to an international normalised ratio (INR) of 2.0 to 3.0 with a target value of 2.5; Other Names: warfarin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding: Number of Patients With Any Bleeding Event, During Treatment Period	Participants	154-711 days on treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alanine Transaminase (ALAT): Number of Patients With ALAT>=3xULN, Post Baseline	ULN=Upper limit of Normal	From baseline to Follow up
Bilirubin: Number of Patients With Bilirubin>=2xULN, Post Baseline		From baseline to Follow up
Creatinine: Absolute Change From Baseline, at End of Treatment		Baseline and End of treatment
D-dimer:Median and Quartile Range at End of Treatment	Median (Lower Quartile-Upper Quartile ), ng/mL	End of treatment
Activated Partial Thromboplastin Time (APTT): Absolute Change From Baseline to End of Treatment	Median Full range, Seconds	Baseline and End of treatment
Electroconvulsive Therapy (ECT): Absolute Change From Baseline to End of Treatment		Baseline and End of Treatment
AZD0837: Plasma Concentration of AZD0837 at End of Treatment		End of treatment
AR-H067637XX, the Active Major Metabolite of AD0837: Plasma Concentration of AR-H067637XX, at End of Treatment		154-711 days on treatment

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Lars Hvilstedt Rasmussen, MD, PhD, FESC, Head of Cardiology at Heart Centre Aalborg Aarhus University Hospital DK 9100 Aalborg Denmark

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: March 19, 2008
• First Submitted That Met QC Criteria: March 25, 2008
• First Posted (Estimate): March 28, 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; Anticoagulants; Warfarin
• Other Study ID Numbers: D1250C00042