A controlled, randomised, double-blind, double-dummy, parallel-group, phase III, multicenter study to evaluate efficacy and safety of the oral direct thrombin inhibitor AZD0837 compared to warfarin for the prevention of stroke and systemic embolic events (SEE) in patients with atrial fibrillation (ASSURE-AF) - ASSURE-AF

Conditions: the prevention of stroke and systemic embolic events (SEE) in patients with non-valvular atrial fibrillation (AF)
MedDRA version: 9.1Level: LLTClassification code 10003658Term: Atrial fibrillation

Registration Number: EUCTR2008-003698-42-FR

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 14600

Inclusion Criteria

1.Provision of informed consent prior to any study specific procedures
2.Female or male aged =18 years
3.Rhythm verification
Patient with paroxysmal AF: Clinically significant paroxysmal AF with at least one documented episode of AF within 12 months. The AF can be documented by 12 lead electrocardiogram (ECG), Holter, event recorder or telemetry, but not by pacemaker
OR
Patient with permanent or persistent AF: AF documented on two occasions >7 days apart within 12 months. The AF can be documented by 12 lead ECG, Holter, event recorder or telemetry, but not by pacemaker
4.Stroke risk classification:
At least one of the following risk factors:
·Prior ischaemic stroke, TIA 6 and/or systemic embolism
·Patient aged =75 years
If neither of the risk factors above, at least two of the following risk factors are required:
·Hypertension
·Symptomatic CHF and/or left ventricular ejection fraction (LVEF) <=35%
·Diabetes mellitus
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Women of childbearing potential without a reliable form of contraception, as judged by the Investigator, before and during participation in the study
2.Lactation
3.AF secondary to a current reversible disorder, (eg, hyperthyroidism, isolated postoperative AF, drugs and pulmonary embolism)
4.Allergic and/or intolerant to VKA
5.Valvular heart disease if
·Any mitral valve prosthesis, or
·Mechanical valve prosthesis, or
·Mitral stenosis, or
·Any other valvular heart disease considered to significantly increase the risk of thromboembolic events or considered hemodynamically significant or expected to require surgical intervention during the course of the study
6.Active infective endocarditis
7.Any condition other than AF requiring chronic anticoagulation treatment
8.Myocardial Infarction (MI), heart surgery (eg, coronary artery bypass grafting, CABG) and/or percutaneous coronary intervention (PCI) within the 3 months prior to enrolment. Any prior PCI requiring clopidogrel treatment at the time of enrolment
9.Stroke, TIA and/or systemic embolism within the previous 14 days prior to randomisation
10.Known haemorrhagic disorders and/or conditions associated with increased risk of major bleeding
11.Severe renal impairment (calculated creatinine clearance (CrCL) <30 mL/min)
12.Known hepatic disease and/or ALT >3xULN and/or bilirubin >2xULN
13.Uncontrolled hypertension, systolic blood pressure =180 mmHg
14.Anemia (Hb<100g/L = 6.2 mmol/L) and/or platelet count <100x10 9/L
15.Planned pulmonary vein ablation procedure, PCI or major surgery. Planned cardioversion (direct current (DC) or pharmacological) within 1 month of randomisation.
16.Other serious disease that gives an estimated survival less than 12 months, any condition making a patient too frail to participate in the study, and/or inability to complete the study according to the protocol. Severe neurological deficit or disability that would interfere with the detection and/or assessment of a new cerebrovascular event
17.Known drug addiction and/or alcohol abuse
18.Previous enrolment or randomisation of treatment in the present study and/or participation in a previous study with AZD0837
19.Participation in another clinical study with IP and/or intervention during the last 3 months
20.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to demonstrate that AZD0837 is non-inferior to warfarin, aiming for an INR 2.0 to 3.0, target 2.5, in the prevention of the composite outcome variable of stroke and SEE.;Primary end point(s): Stroke or systemic embolic event;Secondary Objective: 1. To demonstrate that AZD0837 is associated with a lower risk of bleeding events compared to warfarin, aiming for an INR 2.0 to 3.0, target 2.5.<br>2. To demonstrate that AZD0837 is superior to warfarin, aiming for an INR 2.0 to 3.0, target 2.5, in the composite outcome variable of stroke, SEE, CV mortality, clinically relevant non-major bleeding and major bleeding events.<br>3. To evaluate the overall safety profile of AZD0837 compared to warfarin by assessment of AEs, bleeding events, laboratory safety variables, physical examination, electrocardiogram (ECG), vital signs and treatment discontinuation due to AEs.

Secondary Outcome Measures