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Clarification of Optimal Anticoagulation Through Genetics (COAG)

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00839657
First received: February 6, 2009
Last updated: April 19, 2016
Last verified: May 2013
History of Changes
  Purpose
Individuals taking warfarin often need frequent dose changes as the international normalized ratio (INR) gets too high or too low which could result in a higher risk of thromboembolism, bleeding and early discontinuation of a highly useful therapy. This study will compare two approaches to warfarin dosing to examine the utility of using genetic information for warfarin dosing.

Condition Intervention Phase
Stroke
Venous Thrombosis
Atrial Fibrillation
Atrial Flutter
 Behavioral: Genotype-guided dosing algorithm for warfarin
Behavioral: Clinical-guided dosing algorithm for warfarin
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Multi-Center, Double-Blind Clinical Trial to Evaluate the Use of Clinical Plus Genetic Information to Guide Warfarin Therapy Initiation and Improve Anticoagulation Control for Patients

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Percentage of time participants spend within the therapeutic INR range (PTTR) [ Time Frame: Measured during the first 4 weeks of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Occurrence of INR greater than 4 or serious clinical event [ Time Frame: Measured during the first 4 weeks ] [ Designated as safety issue: Yes ]
Enrollment: 1015
Study Start Date: September 2009
Study Completion Date: November 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Genotype-guided dosing algorithm for warfarin
 Behavioral: Genotype-guided dosing algorithm for warfarin
Initial dosing of warfarin for the first 3-4 days of treatment will be determined by an algorithm that uses clinical and genetic information. Following this initiation dose of warfarin, a second dose adjustment will be made after 3 and/or 4 doses of warfarin using a dose revision algorithm that incorporates the clinical and genetic information.
Active Comparator: 2
Clinical-guided dosing algorithm for warfarin
 Behavioral: Clinical-guided dosing algorithm for warfarin
Initial dosing of warfarin for the first 3-4 days of treatment will be determined by an algorithm that uses clinical information. Following this initiation dose of warfarin, a second dose adjustment will be made after 3 and/or 4 doses of warfarin using a dose revision algorithm that incorporates the clinical information.

Detailed Description:
The objective of the Clarification of Optimal Anticoagulation through Genetics (COAG) trial is to conduct a 1,022 participant, multicenter, double-blind, randomized trial comparing two approaches to guiding warfarin therapy initiation: 1) initiation of warfarin therapy based on algorithms using clinical information and an individual's genotype using genes known to influence warfarin response ("genotype-guided dosing"), and 2) initiation of warfarin therapy based on algorithms using only clinical information ("clinical-guided dosing"). The study hypothesis is that the use of genetic and clinical information for selecting the dose of warfarin during the initial dosing period will lead to improvement in stability of anticoagulation(AC) relative to a strategy that incorporates only clinical information (without genetics) for initial dosing. Each study arm will include a baseline dose initiation algorithm and a dose revision algorithm applied over the first 4 to 5 doses of warfarin therapy. By comparing the two strategies in this trial, the study will be able to determine if genetic information provides added benefit above and beyond what can be gleaned simply with clinical information. This study is a proof-of-concept efficacy trial. Efficacy is defined as a measure of whether, under optimal application, dosing algorithms will lead to improvement in care. The trial will thus answer the question: "can the use of clinical plus genetic information lead to an improvement in anticoagulation control above and beyond the use of only clinical information during the initiation of warfarin, when applied in a uniform and optimal manner to all patients?" Because efficacy has not yet been established for genotype-guided dosing of warfarin, it is important to first test whether this approach can, indeed, improve anticoagulation outcomes under controlled conditions.
  Eligibility
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willingness and ability to sign informed consent
  • Able to be followed in outpatient AC clinic
  • Expected duration of warfarin therapy of at least 1 month
  • AC management for the patient will be performed in-hospital and as an outpatient by clinicians that will adhere to the study dosing algorithms and dose titration plans
  • Target INR 2-3

Exclusion Criteria:

  • Currently taking warfarin
  • Prior warfarin therapy with known required stable dose
  • Clinician opinion that warfarin dosing needs to be adjusted for reasons not accounted for by dosing algorithm
  • Abnormal baseline INR (off warfarin) (e.g., due to liver disease, antiphospholipid antibody)
  • Contraindication to warfarin treatment for at least 3 months
  • Life expectancy of less than 1 year
  • Pregnant women or child-bearing women not using medically approved method of birth control (requires negative pregnancy test to exclude pregnancy in child-bearing women)
  • Inability to follow-up on a regular basis with anticoagulation practitioners participating in the trial
  • Any factors likely to limit adherence to warfarin
  • Cognitive or other causes of inability to provide informed consent or follow study procedures
  • Participating in another trial that prohibits participation in the COAG trial or planned enrollment in such a trial within the first 6 months of warfarin therapy
  • Estimated blood loss of more than 1,000 cc requiring blood transfusions within 48 hours prior to randomization
  • Genotype (CYP2C9 or VKORC1) known to participant from prior testing
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00839657

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35249
United States, California
University of California San Francisco
San Francisco, California, United States, 04143-0131
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610-0486
United States, Georgia
Georgia Health Sciences University
Augusta, Georgia, United States, 30912
United States, Louisiana
Tulane University Health Science Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland School of Medicine
Baltimore, Maryland, United States, 21201
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Minnesota
Mayo Clinic College of Medicine
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555
United States, Utah
Intermountain Medical Center
Murray, Utah, United States, 84157-7000
University of Utah Health Care
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
Marshfield Clinical Research Foundation
Marshfield, Wisconsin, United States, 54449
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Bristol-Myers Squibb
Investigators
Principal Investigator: Stephen E Kimmel, MD, MSCE University of Pennsylvania
  More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00839657     History of Changes
Other Study ID Numbers: 623  N01 HV88210  HHSN268200800003C 
Study First Received: February 6, 2009
Last Updated: April 19, 2016
Health Authority: United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Embolism
Thrombosis

Additional relevant MeSH terms:
Atrial Fibrillation
Thrombosis
Venous Thrombosis
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
 Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Warfarin
Anticoagulants

ClinicalTrials.gov processed this record on October 21, 2016