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 Fibrillatio

• Conditions: Paroxysmal, persistent or permanent nonvalvular atrial fibrillation; MedDRA version: 8.1Level: LLTClassification code 10003658Term: Atrial fibrillation

• Registration Number: EUCTR2006-005437-38-AT
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-03
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

Signed informed consent given by the patient before any study-specific procedures are initiated.

Paroxysmal, persistent or permanent nonvalvular AF (NVAF) verified by at least two ECGs in the last year separated by at least one week; for:
Patients not on VKA treatment: the second ECG should be carried out within the 2 weeks prior to randomization.
VKA treated patients: the second ECG should be carried out within the 12 weeks prior to randomization.

In addition to AF the patient must have one or more risk factors according to the following:

Either one of the following risk factors (high risk patient):
- Previous cerebral ischemic attack (stroke or TIA, >30 days prior to randomization)
- Previous systemic embolism

or at least one of the following risk factors (1 risk factor = moderate risk patient, 2 or more risk factors = high risk patient):
- Age =75 years
- Symptomatic congestive heart failure (CHF)
- Impaired left ventricular systolic function
- Diabetes mellitus
- Hypertension requiring anti-hypertensive treatment
(Hypertensive patients who are enrolled and randomized into the study should be well controlled and have antihypertensive treatment aiming for a blood pressure <160/100 mmHg).

For inclusion in the genetic research (see Appendix D), patients must fulfil the following criterion:

Provision of informed consent for genetic research

If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent.

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

Aged <18 years at randomization

Weight <40 kg at enrolment

Child bearing potential, ie women must be either post-menopausal a, permanently sterilised or, if of childbearing potential, must have a negative pregnancy test prior to initiation of study drug and use a reliable form of contraception b before and during participation in the study.
a Post menopausal patients are defined as patients with: natural or induced menopause with last menstruation >1 year ago or bilateral oophorectomy.
b Reliable form of contraception is defined as: double-barrier method (condoms with spermicide, diaphragm with spermicide), oral contraceptive, implant, long term injectable contraceptive, intrauterine device or tubal ligation. However, female patients using hormonal anti conception method (oral, transdermal, vaginal ring or combination injectables) must agree to use an additional barrier method for contraception (condom or diaphragm).

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

Myocardial infarction, heart surgery (eg coronary artery bypass graft, CABG) or percutaneous transluminal coronary angioplasty (PTCA) within the previous three months prior to randomization

Stroke or transient ischaemic attack (TIA) and/or systemic embolism within the previous 30 days prior to randomization

Conditions associated with increased risk of major bleeding for example:
- history of intracranial bleeding
- history of bleeding gastrointestinal disorder and/or endoscopically verified ulcer disease within the last year prior to randomization
- major surgical procedure or trauma two weeks prior to randomization

Diastolic blood pressure (DBP) >100 mmHg or systolic blood pressure (SBP) >180 mmHg with or without antihypertensive treatment

Renal impairment (calculated creatinine clearance <30 ml/min)

Known hepatic disease and/or ALAT >3xULN at enrolment

History or presence of Human Immunodeficiency Virus (HIV) or infectious hepatitis including known HbSAg positive or antibodies against Hepatitis C

Known Gilberts syndrome

Anaemia (Hb<100 g/L = 6.2 mmol/L)

Platelet count <100 x 109/L

Treatment with antiplatelet other than ASA =100 mg/day or fibrinolytic agents within 10 days before randomization

Planned cardioversion or surgery during the study

Other serious disease that give a calculated survival less than 12 months or any condition making a patient too frail to participate in the study

Known drug addiction and/or alcohol abuse

Inability to complete the study according to the protocol

Previous enrolment or randomization of treatment in the present study. Participating in any other clinical study within 4 weeks (in UK within 12 weeks) prior to enrolment

Treatment with AZD0837 in previous or ongoing AZD0837 study(ies)

Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified