Clarification of Optimal Anticoagulation Through Genetics
COAG
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
3 other identifiers
interventional
1,015
1 country
18
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 stroke
Started Sep 2009
Typical duration for phase_3 stroke
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 6, 2009
CompletedFirst Posted
Study publicly available on registry
February 9, 2009
CompletedStudy Start
First participant enrolled
September 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2013
CompletedApril 20, 2016
May 1, 2013
3.6 years
February 6, 2009
April 19, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of time participants spend within the therapeutic INR range (PTTR)
Measured during the first 4 weeks of therapy
Secondary Outcomes (1)
Occurrence of INR greater than 4 or serious clinical event
Measured during the first 4 weeks
Study Arms (2)
1
EXPERIMENTALGenotype-guided dosing algorithm for warfarin
2
ACTIVE COMPARATORClinical-guided dosing algorithm for warfarin
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
University of California San Francisco
San Francisco, California, 04143-0131, United States
University of Florida
Gainesville, Florida, 32610-0486, United States
Georgia Health Sciences University
Augusta, Georgia, 30912, United States
Tulane University Health Science Center
New Orleans, Louisiana, 70112, United States
University of Maryland School of Medicine
Baltimore, Maryland, 21201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Mayo Clinic College of Medicine
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mount Sinai School of Medicine
New York, New York, 10029, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Duke University
Durham, North Carolina, 27710, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Vanderbilt University
Nashville, Tennessee, 37232, United States
University of Texas Medical Branch
Galveston, Texas, 77555, United States
Intermountain Medical Center
Murray, Utah, 84157-7000, United States
University of Utah Health Care
Salt Lake City, Utah, 84132, United States
Marshfield Clinical Research Foundation
Marshfield, Wisconsin, 54449, United States
Related Publications (4)
Joo J, Geller NL, French B, Kimmel SE, Rosenberg Y, Ellenberg JH. Prospective alpha allocation in the Clarification of Optimal Anticoagulation through Genetics (COAG) trial. Clin Trials. 2010 Oct;7(5):597-604. doi: 10.1177/1740774510381285. Epub 2010 Aug 6.
PMID: 20693186BACKGROUNDKimmel SE, French B, Anderson JL, Gage BF, Johnson JA, Rosenberg YD, Geller NL, Kasner SE, Eby CS, Joo J, Caldwell MD, Goldhaber SZ, Hart RG, Cifelli D, Madigan R, Brensinger CM, Goldberg S, Califf RM, Ellenberg JH. Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial. Am Heart J. 2013 Sep;166(3):435-41. doi: 10.1016/j.ahj.2013.04.009. Epub 2013 Jul 12.
PMID: 24016491BACKGROUNDKimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.
PMID: 24251361RESULTFrench B, Joo J, Geller NL, Kimmel SE, Rosenberg Y, Anderson JL, Gage BF, Johnson JA, Ellenberg JH; COAG (Clarification of Optimal Anticoagulation through Genetics) Investigators. Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial. Trials. 2010 Nov 17;11:108. doi: 10.1186/1745-6215-11-108.
PMID: 21083927DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen E Kimmel, MD, MSCE
University of Pennsylvania
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 6, 2009
First Posted
February 9, 2009
Study Start
September 1, 2009
Primary Completion
April 1, 2013
Study Completion
November 1, 2013
Last Updated
April 20, 2016
Record last verified: 2013-05