A PHASE 2, RANDOMIZED, PARALLEL GROUP, DOSE-FINDING, MULTICENTER, MULTINATIONAL STUDY OF THE SAFETY, TOLERABILITY AND PILOT EFFICACY OF THREE BLINDED DOSES OF THE ORAL FACTOR Xa INHIBITOR BETRIXABAN COMPARED WITH OPEN- LABEL, DOSE-ADJUSTED WARFARIN IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION - EXPLORE Xa
- Conditions
- Antithrombotic treatment for prevention of stroke in patients with non-valvular atrial fibrillationMedDRA version: 9.1Level: LLTClassification code 10003658Term: Atrial fibrillation
- Registration Number
- EUCTR2008-005977-37-DE
- Lead Sponsor
- Portola Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
1.Male or female, age =18 years.
2.If the patient is a woman, she must be without reproductive potential (i.e., postmenopausal for =2 years or after hysterectomy).
3.AF or atrial flutter at the time of enrollment (randomization) or documented within the last year by Holter, ECG, rhythm strip, pacemaker or other intracardiac recording, resulting in an indication for anticoagulation with warfarin or other vitamin K antagonist in the opinion of the treating physician.
4.One or more of the following risk factor(s) for stroke:
a.Age 75 years or older.
b.Prior stroke, TIA or systemic (i.e., non- central nervous system) embolus at least 30 days remote from the time of screening.
c.Symptomatic congestive heart failure within 3 months or left ventricular dysfunction with an LVEF =45% by echocardiography, radionuclide study or contrast angiography.
d.Hypertension requiring pharmacological treatment.
e.Diabetes.
f.Age of 55 years or older and previous coronary artery disease or known peripheral artery disease.
5. INR < 2.2 at the time of randomization
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
1.Body weight less than 40 kg (88 lbs).
2.Need for either hemodialysis or peritoneal dialysis (or likely to require it within one year).
3.AF due to reversible causes (e.g., thyrotoxicosis, pericarditis, cardiac surgery, pulmonary embolism).
4.Mechanical prosthetic valve (bioprosthetic valve is allowed) or valvular disease likely to be operated on within one year.
5.Active bleeding or history (including family history) or symptoms of a congenital or acquired bleeding disorder or vascular malformation; or a history of intracranial, retroperitoneal, or intraocular bleeding within the last 6 months; or is felt to be at high risk for bleeding for other reasons including from significant liver disease. This also includes gastrointestinal bleeding within 90 days before randomization or endoscopically verified ulcer disease within 30 days of screening.
6.Conditions other than AF that require chronic anticoagulation (e.g. prosthetic mechanical heart valve).
7.Persistent, uncontrolled hypertension (SBP >160 mm Hg on repeated measurements).
8.Active infective endocarditis.
9.Scheduled major surgery.
10.Planned pulmonary vein ablation or surgical procedure for cure of AF or flutter.
11.Recent ischemic stroke, systemic embolic event or acute coronary syndrome within 30 days.
12.Severe co-morbid condition with life expectancy of =1 year.
13.Previous known history of genetic coagulopathy (e.g., Factor V Leiden, Protein C Deficiency, Protein S Deficiency, Antiphospholipid Syndrome, etc.).
14.Evidence at Screening of:a.Platelet count <100,000/mm3. b.Serum alanine aminotransferase (ALT) or aspirate aminotransferase (AST) >2.5 times ULN.c.A history (including family history) of Long QT Syndrome”.
15.Aspirin >162 mg daily.
16.Use of verapamil (pending the availability of a drug interaction study with betrixaban).
17.Active alcohol or drug abuse, or psychosocial reasons that make study participation impractical.
18.Use of an investigational drug or device within the past 30 days.
19.Inability to comply with INR monitoring or other protocol-related activities.
20. Positive stool occult blood test, except if explained by a known diagnosis indicating a low risk of bleeding (e.g. hemorrhoids or benign polyp)
21. Scheduled cardioversion or those patients who are likely to undergo cardioversion in the next 1 year. Patients who have had cardioversion at least 30 days prior to screening can be entered in the study.
22.Unable to give written informed consent.
23. A known atrial or ventricular thrombus
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective of the trial is to assess the safety and tolerability of betrixaban at doses of 40 mg, 60 mg and 80 mg given orally once a day for at least 3 months compared to a dose-adjusted Vitamin K antagonist in patients with non-valvular AF.;Secondary Objective: To provide preliminary efficacy data on betrixaban at fixed doses of 40 mg, 60 mg and 80 mg given orally once a day for at least 3 months compared to a dose-adjusted vitamin K antagonist in patients with non-valvular AF.<br><br>To assess the PK and PD of betrixaban at the above doses in the target population.;Primary end point(s): The primary endpoint will be the time to occurrence of major or clinically relevant non-major bleeding.
- Secondary Outcome Measures
Name Time Method