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|
- Primary end point: 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). Secondary end points: 1) time to first therapeutic INR, 2) per-patient percentage of INRs out of therapeutic range, 3) time to stable anticoagulation, and 4) proportion of patients with serious adverse clinical events, defined as INR > 4.0, use of vitamin K, major bleeding events 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)|
|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|