- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00377143
PRospective Evaluation Comparing Initiation of Warfarin StrategiEs (PRECISE): Pharmacogenetic-guided Versus Usual Care
February 14, 2012 updated by: University of Florida
Warfarin (also called Coumadin®) is an anticoagulant drug (blood thinner) given to patients to help prevent blood clots from forming or to help prevent the growth of an existing blood clot.
The purpose of this study is to collect information on a possible method used to determine the best warfarin dose for people before they start warfarin.
This study will focus on finding out if a person's stable dose can be better predicted by using a new approach (called "pharmacogenetic-guided dosing") compared to the current warfarin dosing method.
The pharmacogenetic-guided dosing method (the new warfarin dosing method) will use a person's specific health and genetic information to calculate a patient's warfarin dose at the beginning of warfarin treatment.
The hope is that through this research, we may someday be able to use an individual's genetic information to guide the selection of their specific warfarin dose at the beginning of treatment, leading to precise warfarin dosing and less need for the current trial and error process.
Study Overview
Status
Withdrawn
Conditions
Intervention / Treatment
Detailed Description
Warfarin is the mainstay of therapy in preventing venous thromboembolism (VTE), pulmonary embolism (PE), and subsequent morbidity and mortality.
Despite its proven efficacy in reducing the advent of clot formation, patient-specific warfarin dosing is difficult to predict, with the initial dose regimen often resulting in supra- and subtherapeutic anticoagulation, and subsequently increasing patients' risk of bleeding or embolism.
It has been shown that interpatient warfarin dosing variability is due in part to genetic variations found in the cytochrome P450 2C9 metabolism pathway (CYP2C9), as well as proteins involved in the coagulation cascade, most importantly vitamin K epoxide reductase complex subunit 1 (VKORC1).
A recent retrospective study has shown that these two genes in addition to several clinical/demographic factors account for greater than 58% of the variation in patient-specific warfarin doses.
However, there have been no studies documenting prospective use of this information in selecting an initial warfarin dose.
Hypothesis: Stable therapeutic management of warfarin therapy can be more precisely achieved when patients are prospectively dosed based on a pharmacogenetic-guided dosing equation compared to usual care.
Aim a: To determine if pharmacogenetic-guided dosing of warfarin is superior to usual care, when defined as the accuracy of the initial versus the stable warfarin dose.
This will be assessed as the mean absolute difference in initial versus stable dose.
Aim b: To determine if a stable warfarin dose is more quickly achieved using the pharmacogenetic-guided dosing equation compared to usual care.
This will be assessed as time to stable dose.
Aim c: To determine if pharmacogenetic-guided dosing is superior to usual care in terms of overdosing and underdosing patients.
This will be assessed as the fraction of the population overdosed and the fraction of population underdosed by the two methods.
We propose to evaluate a pharmacogenetic-guided dosing approach compared to usual care in the initiation of warfarin management.
The selected pharmacogenetic-guided equation is a validated equation that includes both genetic and clinical factors and is relatively easy to incorporate into current clinical practice.
Patients newly initiating warfarin therapy in a hospital setting will be randomized to receive either pharmacogenetic-guided or usual care, with follow-up anticoagulation management services provided by the University of Florida Health System Anticoagulation Clinic.
Prospectively determining patients' stable dose has important clinical implications in today's management of warfarin therapy.
Being able to predetermine a patient's stable dose upon initiation of therapy has the potential to decrease the time spent in supra- and subtherapeutic anticoagulation and reduce the number of clinic visits required to achieve a stable dose.
Therefore we propose this study to test if using genotype data in determining the initial warfarin dose is more effective than usual care in predicting stable dose.
If we can document the value of such an approach, this will provide the level of evidence needed to translate pharmacogenetic-guided dosing of warfarin into clinical practice.
Study Type
Interventional
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Gainesville, Florida, United States, 32610
- Shands at the University of Florida
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Newly initiating warfarin
Exclusion Criteria:
- Previous use of warfarin
- Cancer
- Hepatic Disease
- History of alcoholism
- Diarrheal illness
- Febrile Illness
- Blood dyscrasias
- Pregnancy
- Medical plan to hold warfarin administration before stable dose is achieved (ie. for surgical intervention)
- Dementia
- Active bleed
- Aneurysm
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Accuracy of the initial versus the stable warfarin dose, measured as mean absolute difference in initial versus stable dose
|
Secondary Outcome Measures
Outcome Measure |
---|
Time to stable dose
|
The frequency of subtherapeutic and supratherapeutic international normalized ratio (INR) measurements
|
The fraction of population overdosed and underdosed at warfarin initiation
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Julie A Johnson, Pharm.D., University of Florida
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2006
Primary Completion (Actual)
August 1, 2006
Study Registration Dates
First Submitted
September 13, 2006
First Submitted That Met QC Criteria
September 13, 2006
First Posted (Estimate)
September 15, 2006
Study Record Updates
Last Update Posted (Estimate)
February 16, 2012
Last Update Submitted That Met QC Criteria
February 14, 2012
Last Verified
September 1, 2011
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 131-2006
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Blood Coagulation Disorders
-
VarmX B.V.RecruitingCoagulation DisorderNetherlands
-
Groupe Hospitalier Paris Saint JosephCompletedCoagulation DisorderFrance
-
Cairo UniversityRecruitingCoagulation DisorderEgypt
-
Stony Brook UniversityCompletedCoagulation DisorderUnited States
-
HemoSonics LLCCompleted
-
Kyowa Kirin Co., Ltd.CompletedDisseminated Intravascular Coagulation (DIC)Japan
-
TakedaTakeda Development Center Americas, Inc.RecruitingCoagulation DisorderBelgium, Spain, United States, Canada, Germany, France, Austria, Netherlands
-
Fondazione Policlinico Universitario Agostino Gemelli...Completed
-
VarmX B.V.Completed
Clinical Trials on Warfarin Dosing
-
Chinese PLA General HospitalUnknownAtrial Fibrillation | Deep Vein Thrombosis | Pulmonary Embolism | Heart Valve DiseaseChina
-
Gwen McMillinCompletedBleeding | Venous ThromboembolismUnited States
-
National Heart, Lung, and Blood Institute (NHLBI)Bristol-Myers SquibbCompletedStroke | Venous Thrombosis | Atrial Fibrillation | Atrial FlutterUnited States
-
Intermountain Health Care, Inc.Deseret Foundation; LDS Hospital Cardiovascular ResearchCompletedAtrial Fibrillation | Deep Vein Thrombosis | Pulmonary EmbolismUnited States
-
Academia Sinica, TaiwanChina Medical University Hospital; Chang Gung Memorial Hospital; Kaohsiung Medical...CompletedStroke | Venous Thrombosis | Atrial Fibrillation | Atrial FlutterTaiwan
-
Robert PendletonUniversity of LouisvilleCompleted
-
De Montfort UniversityUniversity Hospitals, LeicesterUnknownCongenital Heart Defects
-
Intermountain Health Care, Inc.CompletedThromboembolismUnited States
-
Aalborg University HospitalCompletedAnticoagulation
-
McMaster UniversityEpitome PharmaceuticalsTerminatedHypoprothrombinemiaCanada