Study to Develop a Reliable Nomogram That Incorporates Clinical and Genetic Information

This study has been completed.
Sponsor:
Collaborators:
Massachusetts General Hospital
Newton-Wellesley Hospital
Spaulding Rehabilitation Hospital
Information provided by (Responsible Party):
Mark Alan Creager, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00401414
First received: November 16, 2006
Last updated: July 30, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Pulmonary Embolism
Deep Vein Thrombosis
Atrial Fibrillation
Drug: Warfarin

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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).


Enrollment: 344
Study Start Date: January 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Warfarin
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.
Drug: Warfarin
2 mg tablets take as directed by study staff (based on INR)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years old
  2. Any newly diagnosed condition that will require treatment with therapeutic doses of warfarin for at least 4-6 weeks, e.g. deep venous thrombosis (DVT), pulmonary embolism (PE), atrial fibrillation (AF), orthopedic surgery, etc.
  3. Written informed consent

Exclusion Criteria:

  1. Current treatment with warfarin
  2. Contraindication to therapeutic anticoagulation:

    • Active major bleeding
    • History of intracranial bleeding
    • Surgery, delivery, organ biopsy within 3 days
    • Gastrointestinal bleeding within 10 days
    • Major trauma within 3 days
    • Head injury requiring hospitalization within 3 months
    • Intracranial tumor
    • Neurosurgery or ophthalmologic surgery within the past month
  3. Life expectancy < 3 months
  4. Pregnancy
  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: NCT00401414

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Brigham and Women's Hospital
Massachusetts General Hospital
Newton-Wellesley Hospital
Spaulding Rehabilitation Hospital
Investigators
Principal Investigator: Mark A Creager, MD Brigham and Women's Hospital
  More Information

Additional Information:
Publications:

Responsible Party: Mark Alan Creager, MD, Director, Vascular Center, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00401414     History of Changes
Other Study ID Numbers: 2006-P-001896
Study First Received: November 16, 2006
Results First Received: March 20, 2013
Last Updated: July 30, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Warfarin
Thrombosis
Genetics
Nomogram
Pulmonary Embolism
Deep Vein Thrombosis
Dosing
INR
Anticoagulation
Therapy
Orthopedic Surgery

Additional relevant MeSH terms:
Atrial Fibrillation
Thrombosis
Pulmonary Embolism
Venous Thrombosis
Embolism
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Lung Diseases
Respiratory Tract Diseases
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014