Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000026224
Ethics application status
Approved
Date submitted
18/11/2008
Date registered
15/01/2009
Date last updated
15/01/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation
Scientific 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 Subjects with Nonvalvular Atrial
Fibrillation
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke and Systemic Embolism 3852 0
Condition category
Condition code
Cardiovascular 4048 4048 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Apixaban which is Factor Xa inhibitor. From this intervention treatment, we try to determine if apixaban is noninferior to warfarin in the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, in
subjects with Atrial FibrillationF and at least one additional risk factor for stroke.
The mode of administration of the intervention treatment is orally taken tablets. The dosage amount and dosage frequency is 5 mg given twice a day or matching placebo for the treatment period. Subjects will receive either apixaban and warfarin-placebo or apixaban-placebo and warfarin following randomization.
Treatment period: Lasting until the earlier of a subject’s treatment discontinuation or the attainment of 448 primary efficacy events (average of 1.8 yrs of follow-up from
randomization).
Follow up period: Lasting until the latter of 30 days after treatment discontinuation or the attainment of 448 primary efficacy events
Intervention code [1] 3579 0
Treatment: Drugs
Comparator / control treatment
Control treatment is warfarin which is anticoagulant to inhibit vitamine K dependent coagulation factors.
The mode of administration of the comparator treatment is orally 2 mg tablets. The dosage and frequency is warfarin dose titrated to a target International Normalised Ratio range of 2.0 - 3.0 or matching placebo for the treatment period. Subjects will receive either apixaban and warfarin-placebo or apixaban-placebo and warfarin following randomization
Treatment period: Lasting until the earlier of a subject’s treatment discontinuation or the attainment of 448 primary efficacy events (average 1.8 years
of follow-up from randomization).
Follow up period: Lasting until the latter of 30 days after treatment discontinuation or the attainment of 448 primary efficacy events.
Control group
Active

Outcomes
Primary outcome [1] 4947 0
To determine if apixaban is noninferior to warfarin (International Normalised Ratio target range 2.0 - 3.0) in the combined endpoint of stroke (ischemic or emorrhagic) and systemic embolism, in subjects with AF and at least one additional risk factor for stroke
Timepoint [1] 4947 0
At day 4, Week 1, Day 10, Week 2 and Week3, and every month until the latter of 30 days after treatment discontinuation
or the attainment of 448 primary study events.
Secondary outcome [1] 8343 0
To determine, in subjects with Atrial Fibrillation 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
Timepoint [1] 8343 0
At day 4, Week 1, Day 10, Week 2 and Week3, and every month until the latter of 30 days after treatment discontinuation
or the attainment of 448 primary study events.
Secondary outcome [2] 8890 0
To determine, in subjects with Atrial Fibrillation and at least one additional risk factor for stroke, whether apixaban is superior to warfarin in the combined endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism and major bleeding, in warfarin naive subjects.
Timepoint [2] 8890 0
At day 4, Week 1, Day 10, Week 2 and Week3, and every month until the latter of 30 days after treatment discontinuation
or the attainment of 448 primary study events.
Secondary outcome [3] 8891 0
To determine, in subjects with Atrial Fibrillation and at least one additional risk factor for stroke, whether apixaban is superior to warfarin in the combined endpoint of ischemic stroke, hemorrhagic stroke, systemic embolism and major bleeding.
Timepoint [3] 8891 0
At day 4, Week 1, Day 10, Week 2 and Week3, and every month until the latter of 30 days after treatment discontinuation
or the attainment of 448 primary study events.

Eligibility
Key inclusion criteria
- Males and females = 18 yrs with Atrial Fibrillation and one or more of the following risk factors for stroke:
- Age = 75, previous stroke
- Transient Ischemic Attack (TIA) or Systemic Embolism
- Symptomatic congestive heart failure or left ventricular dysfunction with Left Ventricular Ejection Fraction (LVEF) = 40%
- Diabetes mellitus or hypertension requiring pharmacological treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Atrial fibrillation or flutter due to reversible causes (e.g. thyrotoxicosis, pericarditis)

- Clinically significant (moderate or severe) mitral stenosis

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

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

- Persistent, uncontrolled hypertension (systolic Blood Pressure (BP) > 180 mm Hg, or diastolic BP
> 100 mm Hg)

- Planned major surgery

- Planned atrial fibrillation or flutter ablation procedure

- Required treatment with aspirin > 165 mg/day

- Recent ischemic stroke (within 7 days)

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible subjects will be randomized to either apixaban or warfarin titrated to a target International Normalized Ratio (INR) and will be managed
through the Interactive Voice Response System (IVRS).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
At the time of enrollment, each subject will be assigned a unique sequential subject
number by the Interactive Voice Response System (IVRS). The randomization will be stratified by investigative site and prior warfarin/Vitamin K antagonist status (experienced, naïve).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Controlled, Randomized, Double-
Blind, Parallel-Arm.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 1285 0
United States of America
State/province [1] 1285 0

Funding & Sponsors
Funding source category [1] 4031 0
Commercial sector/Industry
Name [1] 4031 0
Bristol-Myers Squibb Australia
Country [1] 4031 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb Australia
Address
Bristol-Myers Squibb Australia
Level 1, 352 Wellington Road
Mulgrave, Vic, 3170
Country
Australia
Secondary sponsor category [1] 3624 0
Commercial sector/Industry
Name [1] 3624 0
PPD Australia
Address [1] 3624 0
Floor 9
5 Queens Road
Melbourne VIC 3004
Country [1] 3624 0
Australia

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The purpose of this study is to compare the safety and effectiveness of apixaban to warfarin in preventing stroke or clots in subjects with atrial fibrillation and risk factors for stroke. Warfarin is a blood thinning medication approved by the Australian TGA for the prevention of stroke in subjects with atrial fibrillation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29058 0
Address 29058 0
Country 29058 0
Phone 29058 0
Fax 29058 0
Email 29058 0
Contact person for public queries
Name 12215 0
Cameron Halyburton
Address 12215 0
Bristol-Myers Squibb Australia
Level 1, 352 Wellington Road
Mulgrave, Vic, 3170
Country 12215 0
Australia
Phone 12215 0
+61 3 85621339
Fax 12215 0
+61 3 85621393
Email 12215 0
cameron.halyburton@bms.com
Contact person for scientific queries
Name 3143 0
Cameron Halyburton
Address 3143 0
Bristol-Myers Squibb Australia
Level 1, 352 Wellington Road
Mulgrave, Vic, 3170
Country 3143 0
Australia
Phone 3143 0
+61 3 85621339
Fax 3143 0
+61 3 85621393
Email 3143 0
cameron.halyburton@bms.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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