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Trial registered on ANZCTR


Registration number
ACTRN12609000132246
Ethics application status
Approved
Date submitted
22/01/2009
Date registered
25/02/2009
Date last updated
25/02/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase 3, randomised, double-blind, double dummy, parallel group, multi-centre, multi-national study for evaluation of efficacy and safety of du-176b verses warfarin in subjects with atrial fibrillation
Scientific title
A phase 3, randomised, double- blind, double dummy, parallel group, multi-center, multi-national study for evaluation of efficacy and safety of du-176b versus warfarin in subjects with atrial fibrillation
Secondary ID [1] 756 0
Clinical Trials.gov; NCT00781391
Universal Trial Number (UTN)
Trial acronym
ENGAGE AF TIMI 48
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 3999 0
Condition category
Condition code
Cardiovascular 4198 4198 0 0
Normal development and function of the cardiovascular system
Cardiovascular 4439 4439 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention Arm 1: Du-176b is taken once daily orally - 60mg
Intervention Arm 2: Du-176b is taken once daily orally - 30mg
The overall duration for intervention 1 and 2 is taken once daily orally for approximately 2 years
Intervention code [1] 3724 0
Treatment: Drugs
Comparator / control treatment
Warfarin - taken orally once daily with dose adjusted to maintain International Normalized Ratio (INR) between 2.0 and 3.0 inclusive. The overall duration the warfarin will be taken is once daily for approximately two years (there are no units of measurement because the number is a ratio)
Control group
Active

Outcomes
Primary outcome [1] 5095 0
The primary objective is to compare DU-176b to warfarin with regard to the composite primary endpoint of stroke and Systemic embolic event (SEE). Each DU-176b regimen will be compared with warfarin for non-inferiority. Any non-inferior DU-176b regimen will be compared with warfarin for superiority.
Stroke and systemic embolic events will be assessed utilising Hospital and Doctor Records
Timepoint [1] 5095 0
2 years, this is an event driven study so will be assessed every time there is an event utnil the number of required events are collected. This could mean that the study is shorter or longer in duration than 2 years. The number of events needed is 448 events in each of the three study arms.
Secondary outcome [1] 8563 0
1. To compare DU-176b to warfarin with regard to major bleeding as well as major plus clinically relevant non-major bleeding.
This outcome will be measured as follows:Hospital and or Doctor records.
Timepoint [1] 8563 0
At study end:this is an event driven study so will be assessed every time there is an event utnil the number of required events are collected. This could mean that the study is shorter or longer in duration than 2 years. There will be 448 events collected from each of the three arms of the study

Eligibility
Key inclusion criteria
1. Male or female subjects with age = 21 years;
2. Able to provide written informed consent;
3. History of Atrial Fibrillation (AF) documented by a 12-lead electrocardiographic reading and/or continuous electrocardiogram (ECG) (e.g., Holter monitoring) consistent with Atrial Fibrillation (AF) (notation of AF as the abnormal rhythm on the local ECG report with evidence of irregularly irregular rhythm and an absence of P-waves on the ECG for diagnosis of AF) within the prior 12 months and for which anticoagulation therapy is indicated and planned for the duration of the study, including subjects with paroxysmal, persistent, or permanent AF and subjects with or without previous vitamin K antagonist (VKA) (including warfarin) experience (it is anticipated that approximately 40% of subjects will be VKA-naive);
4. A moderate to high risk of stroke, as defined by Scoring system Congestive Heart Failure, Hypertension, Age, Diabetes, previous stroke (CHADS2) index score of at least 2, is required to be eligible for the study. The CHADS2 scoring is performed by assigning 1 point each for a history of congestive heart failure, hypertension, age 75 years, or diabetes mellitus; and by assigning 2 points for history of stroke or Trans Ischemic Attack (TIA).
Minimum age
21 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 Transient AF secondary to other reversible disorders
2 Subjects with moderate or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve
3 Subjects with any contraindication for anticoagulant agents;
4 Subjects with conditions associated with high risk of bleeding or have known or suspected hereditary or acquired bleeding disorders
5 Females of childbearing potential including the following:
a)Females with a history of
tubal-ligation;
b) Females less than 2 years
post-menopausal

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)
The Investigator will contact the Interactive Voice Randomisation System (IVRS) after assessing the inclusion and exclusion criteria and before the first administration of study drug. The Investigator should be prepared to provide subject information, including, but not limited to, the following: date of birth, creatinine clearance (CrCL), CHADS2 score, and whether the subject on concomitant verapamil and/or quinidine. The IVRS will allocate the treatment group assignment for the subject.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The specifications for generation of the randomization schedule will be prepared by the study biostatistician and the contract research organization (CRO) in charge of the IVRS. An independent biostatistician (from the CRO responsible for the IVRS), not otherwise part of the study team, will generate the randomization schedule. This is generated by a computer program
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL GROUP
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
19/11/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 1370 0
Argentina
State/province [1] 1370 0
Country [2] 1371 0
Belgium
State/province [2] 1371 0
Country [3] 1372 0
Bosnia and Herzegovina
State/province [3] 1372 0
Country [4] 1373 0
Brazil
State/province [4] 1373 0
Country [5] 1374 0
Bulgaria
State/province [5] 1374 0
Country [6] 1375 0
Canada
State/province [6] 1375 0
Country [7] 1376 0
Chile
State/province [7] 1376 0
Country [8] 1377 0
China
State/province [8] 1377 0
Country [9] 1378 0
Colombia
State/province [9] 1378 0
Country [10] 1379 0
Costa Rica
State/province [10] 1379 0
Country [11] 1380 0
Croatia
State/province [11] 1380 0
Country [12] 1381 0
Czech Republic
State/province [12] 1381 0
Country [13] 1382 0
Denmark
State/province [13] 1382 0
Country [14] 1383 0
Estonia
State/province [14] 1383 0
Country [15] 1384 0
Finland
State/province [15] 1384 0
Country [16] 1385 0
France
State/province [16] 1385 0
Country [17] 1386 0
Germany
State/province [17] 1386 0
Country [18] 1387 0
Greece
State/province [18] 1387 0
Country [19] 1388 0
New Zealand
State/province [19] 1388 0
Country [20] 1389 0
Philippines
State/province [20] 1389 0
Country [21] 1390 0
Thailand
State/province [21] 1390 0
Country [22] 1391 0
United States of America
State/province [22] 1391 0

Funding & Sponsors
Funding source category [1] 4402 0
Commercial sector/Industry
Name [1] 4402 0
Daiichi Sankyo Pharma Development
Country [1] 4402 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Daiichi Sankyo Pharma Development
Address
399 Thornall Street EDISON, NJ USA
Country
United States of America
Secondary sponsor category [1] 3961 0
None
Name [1] 3961 0
Address [1] 3961 0
Country [1] 3961 0
Other collaborator category [1] 535 0
University
Name [1] 535 0
TIMI (Thrombosis in Myocardial Infarction) Study group
Address [1] 535 0
Brigham and Women?s Hospital, 350 Longwood Avenue, Boston, MA 02115
Country [1] 535 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6450 0
Multi-region Ethics Committee
Ethics committee address [1] 6450 0
Ethics committee country [1] 6450 0
New Zealand
Date submitted for ethics approval [1] 6450 0
Approval date [1] 6450 0
Ethics approval number [1] 6450 0
MEC/08/10/135 (EC reference number)]

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29147 0
Address 29147 0
Country 29147 0
Phone 29147 0
Fax 29147 0
Email 29147 0
Contact person for public queries
Name 12304 0
Shirali Patel
Address 12304 0
5927 South Miami Boulevard, Berrington Building, Morrisville, North Carolina 27560
Country 12304 0
United States of America
Phone 12304 0
+ 1 919-998-1452
Fax 12304 0
+ 1 919-462-8247
Email 12304 0
shirali.patel@quintiles.com
Contact person for scientific queries
Name 3232 0
TIMI (Thrombosis in Myocardial Infarction) Study Group
Address 3232 0
Brigham and Women’s Hospital
350 Longwood Avenue
Boston, MA 02115
Country 3232 0
United States of America
Phone 3232 0
+ 1 800 385 4444
Fax 3232 0
+ 1 888 249 5261
Email 3232 0
TIMIENGAGE@PARTNERS.ORG

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No Supporting Document Provided



Results publications and other study-related documents

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