MDACC Study Summary 2007-0049 (Archived)

Study Summary
No. 2007-0049:.......Unspecified......Elie Mouhayar......Cardiology

Study Summary Title



Study Summary Number:	2007-0049

Study Title:	A Phase 3, Active (Warfarin) Controlled, Randomized, Double-Blind, Parallel-Arm Study to Evaluate Efficacy and Safety of Apixaban In Preventing Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation (Bristol-Myers Squibb Pharmaceutical Research Institute Protocol Number CV185030)

Physician

New Patient Referral



Name:	Elie Mouhayar	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Cardiology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-4197 Contact us about clinical trials

General Information



Disease Group:	Unspecified	Supported By:	Bristol-Myers Squibb Pharmaceutical Research Institute

Phase of Study:	Phase III	Return Visit:	48

Treatment Agents:	Apixaban Warfarin	Home Care:	N/A

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	No hospital stay is required.


Description/ Intervention:	The goal of this optional genetic substudy is to collect an additional blood sample and health information for pharmacogenetic (PG) research. PG testing looks at how someone's genes may influence if and how well treatment may affect the disease.

Study Objectives / Outcomes

Primary Objective:
To determine if apixaban is noninferior to warfarin (INR target range 2.0 - 3.0) in the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, in subjects with AF and at least one additional risk factor for stroke

Secondary Objectives:
To determine, in subjects with AF and at least one additional risk factor for stroke, whether
- apixaban is superior to warfarin in the combined endpoint of ischemic stroke, hemorrhagic stroke and systemic embolism
- apixaban is superior to warfarin in the combined endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism and major bleeding, in warfarin naīve subjects
- apixaban is superior to warfarin in the combined endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism and major bleeding.
To compare, in subjects with AF and at least one additional risk factor for stroke, apixaban and warfarin with respect to:
- the composite endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism and all cause death
- the composite endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism, major bleeding and all cause death
- the composite endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism, myocardial infarction and all cause death
- the incidence of major bleeding
To assess the safety of apixaban in subjects with AF and at least one additional risk factor for stroke.

Primary Safety Endpoint: The primary safety endpoint will be time to first occurrence of confirmed major
bleeding.
Secondary Safety Endpoints: The secondary safety outcome for this trial is a composite of confirmed major bleeding and confirmed clinically significant non-major bleeding. Other safety outcome measures will also be assessed, and will include minor bleeds, fractures and other AEs as well as abnormal standard clinical laboratory test results.
All major bleeding and clinically relevant non-major bleeding outcomes will be adjudicated by the CEC.

Primary Efficacy Endpoint: The primary efficacy endpoint will be the time to first occurrence of confirmed ischemic stroke, hemorrhagic stroke or systemic embolism.
Secondary Efficacy Endpoints: The secondary efficacy endpoints will be time to first occurrence of confirmed:
• ischemic stroke
• hemorrhagic stroke
• systemic embolism
• all cause death
• composite of ischemic stroke, hemorrhagic stroke, systemic embolism, major bleeding
• composite of ischemic stroke, hemorrhagic stroke, systemic embolism, all cause death
• composite of ischemic stroke, hemorrhagic stroke, systemic embolism, major bleeding, all cause death
• composite of ischemic stroke, hemorrhagic stroke, systemic embolism, myocardial infarction, all cause death
All efficacy outcomes will be adjudicated by the CEC.

Study Status Information



Study Activation / Registration Date:	06/13/2007

IRB Review and Approval Date:	06/13/2007

Study Type:	Phase Iii

Recruitment Status:	Terminated

Projected Accrual:	18000

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Age >/= 18 years

2) In atrial fibrillation or atrial flutter not due to a reversible cause and documented by ECG at the time of enrollment OR if not in atrial fibrillation/flutter at the time of enrollment, must have atrial fibrillation/flutter documented on two separate occasions, not due to a reversible cause at least 2 weeks apart in the 12 months prior to enrollment. Atrial fibrillation/flutter may be documented by ECG, or as an episode lasting at least one minute on a rhythm strip, Holter recording, or intracardiac electrogram (from an implanted pacemaker or defibrillator)

3) One or more of the following risk factor(s) for stroke: a) Age 75 years or older, b) Prior stroke, TIA or systemic embolus, c) Either symptomatic congestive heart failure within 3 months or left ventricular, dysfunction with an LV ejection fraction (LVEF) </= 40% by echocardiography, radionuclide study or contrast angiography, d) Diabetes mellitus, and e) Hypertension requiring pharmacological treatment

4) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the treatment period of the study or for 2 weeks after the last dose of study medication, whichever is longer, in such a manner that the risk of pregnancy is minimized.

5) WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >/= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL).

6) Even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.

7) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 48 hours prior to the start of investigational product.

8) All subjects must provide signed written informed consent.

Exclusion Criteria:

1) Atrial fibrillation or flutter due to reversible causes (e.g. thyrotoxicosis, pericarditis)

2) Clinically significant (moderate or severe) mitral stenosis

3) Increased bleeding risk that is believed to be a contraindication to oral anticoagulation (e.g. previous intracranial hemorrhage)

4) Conditions other than atrial fibrillation that require chronic anticoagulation (e.g. prosthetic mechanical heart valve)

5) Persistent, uncontrolled hypertension (systolic BP > 180 mm Hg, or diastolic BP > 100 mm Hg)

6) Active infective endocarditis

7) Planned major surgery

8) Planned atrial fibrillation or flutter ablation procedure

9) Use of an unapproved, investigational drug or device within the past 30 days

10) Required treatment with aspirin > 165 mg/day

11) Simultaneous treatment with both aspirin and a thienopyridine (e.g., clopidogrel, ticlopidine)

12) Severe comorbid condition with life expectancy of </= 1 year

13) Active alcohol or drug abuse, or psychosocial reasons that make study participation impractical

14) Recent ischemic stroke (within 7 days)

15) Severe renal insufficiency (serum creatinine > 2.5 mg/dL or a calculated creatinine clearance < 25 mL/min)

16) ALT or AST > 2X ULN or a Total Bilirubin >/= 1.5X ULN (unless an alternative causative factor [e.g., Gilbert's syndrome] is identified)

17) Platelet count </= 100,000/mm^3

18) Hemoglobin < 9 g/dL

19) Inability to comply with INR monitoring

20) Prior randomization into an apixaban clinical study

21) Prisoners or subjects who are involuntarily incarcerated

22) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

23) Women of child bearing potential (WOCBP) unwilling or unable to use an acceptable method to avoid pregnancy:

24) WOCBP using a prohibited contraceptive method

25) WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >/= 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL].

26) Even women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of child bearing potential

27) Women who are pregnant or breastfeeding

28) Women with a positive pregnancy test on enrollment or prior to administration of investigational product.

Links

Registration Number: NCT00412984
Study Information on Clinical Trials Registry (clinicaltrials.gov)