StrokePhase 3COAGNCT00839657
Clarification of Optimal Anticoagulation Through Genetics
A Phase 3 study testing Genotype-guided dosing algorithm for warfarin and Clinical-guided dosing algorithm for warfarin in people with Stroke and Venous Thrombosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 18 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Venous Thrombosis, Atrial Fibrillation
- What is being tested?
- Genotype-guided dosing algorithm for warfarin and Clinical-guided dosing algorithm for warfarin
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,015 participants
- Where
- 18 sitesUnited States
- Study dates
- Sep 2009to Nov 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Georgia Health Sciences University
Augusta, Georgia, 30912
University of Maryland School of Medicine
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Henry Ford Hospital
Detroit, Michigan, 48202
Duke University
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610-0486
University of Texas Medical Branch
Galveston, Texas, 77555
Marshfield Clinical Research Foundation
Marshfield, Wisconsin, 54449
Intermountain Medical Center
Murray, Utah, 84157-7000
Vanderbilt University
Nashville, Tennessee, 37232
Tulane University Health Science Center
New Orleans, Louisiana, 70112
Mount Sinai School of Medicine
New York, New York, 10029
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic College of Medicine
Rochester, Minnesota, 55905
University of Utah Health Care
Salt Lake City, Utah, 84132
University of California San Francisco
San Francisco, California, 04143-0131
Washington University School of Medicine
St Louis, Missouri, 63110
Montefiore Medical Center
The Bronx, New York, 10467
About this study
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
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.
Read the 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.
- Conditions
- Stroke, Venous Thrombosis, Atrial Fibrillation, Atrial Flutter
- Being tested
- Genotype-guided dosing algorithm for warfarin, Clinical-guided dosing algorithm for warfarin
- Keywords
- Embolism, Thrombosis
- Medical subject headings
- Stroke, Venous Thrombosis, Atrial Fibrillation, Atrial Flutter, Embolism, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genotype-guided dosing algorithm for warfarinBehavioural
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.
Clinical-guided dosing algorithm for warfarinBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Genotype-guided dosing algorithm for warfarin Receives: Behavioral: Genotype-guided dosing algorithm for warfarin |
| 2 | Active comparator | Clinical-guided dosing algorithm for warfarin Receives: Behavioral: Clinical-guided dosing algorithm for warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of time participants spend within the therapeutic INR range (PTTR)
Measured: Measured during the first 4 weeks of therapy
Secondary outcomes (1)
Occurrence of INR greater than 4 or serious clinical event
Measured: Measured during the first 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2009 (estimated)
- Study startSep 2009
- Primary completionApr 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1,015 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Stephen E Kimmel, MD, MSCE, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00839657
- Sponsor's protocol ID
- 623
- Other IDs
- N01 HV88210, HHSN268200800003C
- Acronym
- COAG
- Status last verified
- May 2013
- First submitted
- 6 Feb 2009
- Last updated
- 20 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20693186Kimmel 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.
PubMed 24016491Kimmel 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.
PubMed 24251361French 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.
PubMed 21083927
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00839657
- Acronym / sponsor ID
- COAG / 623
- Conditions
- Stroke, Venous Thrombosis, Atrial Fibrillation, Atrial Flutter
- Keywords
- Embolism, Thrombosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,015 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Collaborators
- Bristol-Myers Squibb
- Study start
- Sep 2009
- Primary completion
- Apr 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 9 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Behavioral: Genotype-guided dosing algorithm for warfarinGenotype-guided dosing algorithm for warfarin |
| 2 | Active comparator | Behavioral: Clinical-guided dosing algorithm for warfarinClinical-guided dosing algorithm for warfarin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genotype-guided dosing algorithm for warfarinInitial 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. | Behavioural | 1 |
| Clinical-guided dosing algorithm for warfarinInitial 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. | Behavioural | 2 |
Primary outcome
Percentage of time participants spend within the therapeutic INR range (PTTR)
Time frame: Measured during the first 4 weeks of therapy
1 secondary outcome
Occurrence of INR greater than 4 or serious clinical event
Time frame: Measured during the first 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2016.
- Background: PubMed 20693186Joo 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.
- Background: PubMed 24016491Kimmel 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.
- Results publication: PubMed 24251361Kimmel 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.
- Derived from this study: PubMed 21083927French 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen E Kimmel, MD, MSCE principal investigator
University of Pennsylvania
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Genotype-guided dosing algorithm for warfarin and Clinical-guided dosing algorithm for warfarin in people with Stroke and Venous Thrombosis, run by National Heart, Lung, and Blood Institute (NHLBI) at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of time participants spend within the therapeutic INR range (PTTR) (time frame: Measured during the first 4 weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00839657, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2016.