Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate

This study has been completed.

Sponsor:

Collaborators:

Population Health Research Institute

Uppsala University

Information provided by:

Boehringer Ingelheim Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT00262600

First received: December 6, 2005

Last updated: July 10, 2012

Last verified: July 2012

History of Changes

Results First Received: November 18, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Primary Purpose: Prevention
Conditions:	Atrial Fibrillation Stroke
Interventions:	Drug: warfarin Drug: Dabigatran dose 1 Drug: Dabigatran dose 2

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Dabigatran 110 mg	110 mg twice daily, total daily dose 220 mg
Dabigatran 150 mg	150 mg twice daily, total daily dose 300 mg
Warfarin	Target International Normalized Ratio (INR) of 2.0 to 3.0

Participant Flow: Overall Study

	Dabigatran 110 mg	Dabigatran 150 mg	Warfarin
STARTED	6015	6076	6022
COMPLETED	5780	5824	5756
NOT COMPLETED	235	252	266
Lost to Follow-up	17	31	41
Withdrawal by Subject	128	145	139
Not Treated	32	17	24
Not Specified	58	59	62

Baseline Characteristics

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Reporting Groups

	Description
Dabigatran 110 mg	110 mg twice daily, total daily dose 220 mg
Dabigatran 150 mg	150 mg twice daily, total daily dose 300 mg
Warfarin	Target International Normalized Ratio (INR) of 2.0 to 3.0
Total	Total of all reporting groups

Baseline Measures

	Dabigatran 110 mg	Dabigatran 150 mg	Warfarin	Total
Number of Participants [units: participants]	6015	6076	6022	18113
Age [units: years] Mean ± Standard Deviation	71.4 ± 8.6	71.5 ± 8.8	71.6 ± 8.6	71.5 ± 8.7
Age, Customized [units: Participants]
<65	998	1030	953	2981
65<= and <75	2668	2580	2646	7894
>=75	2349	2466	2423	7238
Gender, Customized [units: participants]
Male	3865	3840	3809	11514
Female	2149	2236	2213	6598
Missing	1	0	0	1
Ethnicity (NIH/OMB) [units: participants]
Not Hispanic or Latino	5593	5660	5615	16868
Hispanic or Latino	421	416	407	1244
Unknown or Not Reported	1	0	0	1
Race/Ethnicity, Customized [units: participants]
White	4208	4268	4203	12679
Black	52	57	67	176
Asian	955	965	955	2875
Other	799	786	797	2382
Missing	1	0	0	1
Region of Enrollment [units: participants]
USA, Canada	2166	2200	2167	6533
Central Europe	707	706	706	2119
Western Europe	1544	1555	1552	4651
Latin America	320	320	316	956
Asia	923	933	926	2782
Other	355	362	355	1072
Smoking history [units: participants]
Non-smoker	2941	2993	3006	8940
Smoker	440	447	448	1335
Ex-smoker	2633	2636	2567	7836
Missing	1	0	1	2
Regular Alcohol Consumption [units: participants]
No	4017	4077	4040	12134
Yes	1996	1999	1981	5976
Missing	2	0	1	3

Outcome Measures

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1. Primary:

Yearly Event Rate for Composite Endpoint of Stroke/SEE [ Time Frame: 36 months ]

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2. Secondary:

Yearly Event Rate for Composite Endpoint of Stroke/SEE/All Cause Death [ Time Frame: 36 months ]

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3. Secondary:

Yearly Event Rate: Composite of Stroke/SEE/PE/MI/Vascular Death [ Time Frame: 36 months ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com

No publications provided by Boehringer Ingelheim Pharmaceuticals

Publications automatically indexed to this study:

Paré G, Eriksson N, Lehr T, Connolly S, Eikelboom J, Ezekowitz MD, Axelsson T, Haertter S, Oldgren J, Reilly P, Siegbahn A, Syvanen AC, Wadelius C, Wadelius M, Zimdahl-Gelling H, Yusuf S, Wallentin L. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013 Apr 2;127(13):1404-12. doi: 10.1161/CIRCULATIONAHA.112.001233. Epub 2013 Mar 6.

Dans AL, Connolly SJ, Wallentin L, Yang S, Nakamya J, Brueckmann M, Ezekowitz M, Oldgren J, Eikelboom JW, Reilly PA, Yusuf S. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation. 2013 Feb 5;127(5):634-40. doi: 10.1161/CIRCULATIONAHA.112.115386. Epub 2012 Dec 27.

Bytzer P, Connolly SJ, Yang S, Ezekowitz M, Formella S, Reilly PA, Aisenberg J. Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial. Clin Gastroenterol Hepatol. 2013 Mar;11(3):246-52.e1-5. doi: 10.1016/j.cgh.2012.10.021. Epub 2012 Oct 24.

Van Spall HG, Wallentin L, Yusuf S, Eikelboom JW, Nieuwlaat R, Yang S, Kabali C, Reilly PA, Ezekowitz MD, Connolly SJ. Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial. Circulation. 2012 Nov 6;126(19):2309-16. doi: 10.1161/CIRCULATIONAHA.112.101808. Epub 2012 Oct 1.

Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchle H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M; RE-LY Investigators. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial. Circulation. 2012 Jul 17;126(3):343-8. Epub 2012 Jun 14.

Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, Reilly PA, Vinereanu D, Siegbahn A, Yusuf S, Wallentin L. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) substudy. Circulation. 2012 Apr 3;125(13):1605-16. Epub 2012 Feb 28.

Hohnloser SH, Oldgren J, Yang S, Wallentin L, Ezekowitz M, Reilly P, Eikelboom J, Brueckmann M, Yusuf S, Connolly SJ. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012 Feb 7;125(5):669-76. Epub 2012 Jan 3.

Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, Kamensky G, Reilly PA, Yang S, Yusuf S, Wallentin L, Connolly SJ; RE-LY Investigators. Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial. Ann Intern Med. 2011 Nov 15;155(10):660-7, W204.

Eikelboom JW, Wallentin L, Connolly SJ, Ezekowitz M, Healey JS, Oldgren J, Yang S, Alings M, Kaatz S, Hohnloser SH, Diener HC, Franzosi MG, Huber K, Reilly P, Varrone J, Yusuf S. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011 May 31;123(21):2363-72. Epub 2011 May 16.

Nagarakanti R, Ezekowitz MD, Oldgren J, Yang S, Chernick M, Aikens TH, Flaker G, Brugada J, Kamensky G, Parekh A, Reilly PA, Yusuf S, Connolly SJ. Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation. 2011 Jan 18;123(2):131-6. Epub 2011 Jan 3.

Ezekowitz MD, Wallentin L, Connolly SJ, Parekh A, Chernick MR, Pogue J, Aikens TH, Yang S, Reilly PA, Lip GY, Yusuf S; RE-LY Steering Committee and Investigators. Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation. Circulation. 2010 Nov 30;122(22):2246-53.

Diener HC, Connolly SJ, Ezekowitz MD, Wallentin L, Reilly PA, Yang S, Xavier D, Di Pasquale G, Yusuf S; RE-LY study group. Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial. Lancet Neurol. 2010 Dec;9(12):1157-63. Epub 2010 Nov 6.

Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. Epub 2009 Aug 30.

Ezekowitz MD, Connolly S, Parekh A, Reilly PA, Varrone J, Wang S, Oldgren J, Themeles E, Wallentin L, Yusuf S. Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran. Am Heart J. 2009 May;157(5):805-10, 810.e1-2.

Responsible Party:	Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT00262600 History of Changes
Other Study ID Numbers:	1160.26, 2005-003894-26
Study First Received:	December 6, 2005
Results First Received:	November 18, 2010
Last Updated:	July 10, 2012
Health Authority:	Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica) Australia: Responsilble Ethics Committee Austria: Federal Office for Safety in Health Care Belgium: Federal Agency for Medicines and Health Products Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia Canada: Health Canada China: Food and Drug Administration Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10 Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: AFFSAPS Germany: Federal Institute for Drugs and Medical Devices Great Britain: MHRA Greece: National Organization for Medicines (EOF) National Ethics Committee Hong Kong: Department of Health Hungary: National Institute of Pharmacy, H-1051 Budapest India: Drug Control General of India Israel: Ministry of Health Italy: Comitato Etico Indipendente - BOLOGNA Japan: Ministry of Health, Labor and Welfare Korea, Republic of: KOREA Food and Drug Administration (KFDA) Malaysia: Drug Control Authority Mexico: Federal Commission for Sanitary Risks Protection Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Norway: Norwegian Medicines Agency (Statens Legemiddelverk) Peru: General Directorate of Pharmaceuticals, Devices, and Drugs Philippines: Bureau of Food and Drug Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: INFARMED - National Authority of Medicines and Health Products, IP Romania: National Medicines Agency, Bucharest Russia: Ministry of Health of the Russian Federation Singapore: Health Sciences Authority Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26 South Africa: MCC Spain: Agencia Española del Medicamento y Productos Sanitarios Sweden: Medical Products Agency Switzerland: Swissmedic Taiwan: Department of Health, Executive Yuan, Taiwan Thailand: Thai Food & Drug Administration Turkey: Ministry of Health Central Ethics Committee Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine) United States: Food and Drug Administration

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