Study to Develop a Reliable Nomogram That Incorporates Clinical and Genetic Information
In this research study, the investigators are trying to find a better way to set the dose of a common blood-thinning medication.
Patients with blood clots or a risk of blood clots (or stroke) sometimes have to take an approved medication called warfarin. Warfarin is a commonly prescribed, approved blood thinning medicine taken by mouth. There is a certain level of warfarin that is best for each patient at a particular time. It is hard for a doctor to choose and maintain the right dose of warfarin for each patient. Too much or too little warfarin in the blood can cause serious health problems.
A "nomogram" is a tool that helps doctors decide on the right dose of warfarin. The usual way for finding the right dose of warfarin is for doctors to take an educated guess and use a "trial and error" approach. Patients have frequent blood tests to help doctors keep track of how well the dose level is working.
Up until now, if a patient had good blood test results over half of the time, that was as well as doctors could do. The purpose of this study is to see whether the investigators can create a reliable new warfarin nomogram that will allow them to dose a patient correctly more often, perhaps about 3 times out of 4. The nomogram the investigators are studying uses information about a patient's health and genes to decide on the best dose of warfarin.
The investigators don't yet have a reliable, safe way to choose the correct dose. In this study, the investigators will use a genetic blood test to try to find a better way. Genes are the parts of each living cell that allow characteristics to be passed on from parents to children. The investigators know that people with certain genes seem to respond to warfarin in a certain way. From a blood sample, the investigators can look at patients' genes and try to predict the response to the blood-thinning medication.
There will be about 500 subjects taking part in this study. They will come from participating Partners' Hospitals, including Brigham and Women's Hospital, Massachusetts General Hospital, Faulkner Hospital, Newton-Wellesley Hospital, Spaulding Rehabilitation Hospital, and North Shore Medical Center. The U.S. Food and Drug Administration (FDA) has approved warfarin for use as a blood thinner.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||CReating an Optimal Warfarin Nomogram (CROWN) Trial|
- Mean Percentage of Time That INR Within Therapeutic Range Using Linear Interpolation (Rosendaal et al). [ Time Frame: 90 Days ] [ Designated as safety issue: No ]
Primary end point: mean percentage of time INR is within therapeutic range. Though target INR was 2.0-3.0, therapeutic INR is considered 1.8-3.2 (allows for INR measurement error and avoids problems inherent in overcorrection).
The international normalized ratio (INR) is one way of presenting prothrombin time test results for people taking the blood-thinning medication warfarin. The INR formula adjusts for variation in laboratory testing methods so that test results can be comparable.
- Time to the First Therapeutic INR. [ Time Frame: 90 Days ] [ Designated as safety issue: No ]The INR (international normalized ratio) is a derived measure of the prothrombin time. In this trial, a therapeutic INR was considered 1.8 to 3.2
- Per-patient Percentage of INRs Out of the Therapeutic Range [ Time Frame: 90 Days ] [ Designated as safety issue: No ]The INR (international normalized ratio) is a derived measure of the prothrombin time. In this trial, a therapeutic INR was considered 1.8 to 3.2
- Time to Stable Anticoagulation (in Days). [ Time Frame: 90 Days ] [ Designated as safety issue: No ]Defined as two consecutive INRs within the therapeutic range >7 days apart and with no dose change during this time.
- Proportion of Patients With Serious Adverse Clinical Events. [ Time Frame: 90 Days ] [ Designated as safety issue: No ]Defined as an INR>4.0, use of vitamin K, major bleeding events (as defined by the Thrombolysis in Myocardial Infarction [TIMI] criteria), thromboembolic events, stroke (all cause), myocardial infarction, and death (all cause).
|Study Start Date:||January 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
We will develop a nomogram for warfarin dosing that uses rapid turnaround genetic testing and monthly nomogram modification (if necessary) to achieve effective and safe warfarin induction and maintenance. More than 70% of the time, we will maintain warfarin naïve patients within the target therapeutic range. The percent of time in the therapeutic range will be analyzed beginning 2 weeks after initiation of warfarin. Analyses will be stratified by the indication for anticoagulation.
2 mg tablets take as directed by study staff (based on INR)
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|United States, Massachusetts|
|Brigham and Women's Hospital|
|Boston, Massachusetts, United States, 02115|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Mark A Creager, MD||Brigham and Women's Hospital|