Trial record 7 of 755 for:    pharmacogenomics OR pharmacogenetics

Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients

This study is currently recruiting participants.
Verified October 2013 by Chinese PLA General Hospital
Sponsor:
Information provided by (Responsible Party):
Tong Yin, Chinese PLA General Hospital
ClinicalTrials.gov Identifier:
NCT01610141
First received: May 30, 2012
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine whether pharmacogenetic guided dosing of warfarin is promising for the improvement of efficiency, therapeutic efficacy, and, especially, safety of warfarin therapy than a dosing regimen without the pharmacogenetic information in Chinese patients initiated on warfarin anticoagulation.


Condition Intervention Phase
Atrial Fibrillation
Deep Vein Thrombosis
Pulmonary Embolism
Heart Valve Disease
Other: Genotype-guided warfarin dosing
Other: Non-genotype guided warfarin dosing
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients

Resource links provided by NLM:


Further study details as provided by Chinese PLA General Hospital:

Primary Outcome Measures:
  • A comparison between the pharmacogenetic and standard arms of the per-patient percentage of out-of-range INRs (<1.5, >3). [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to the first supratherapeutic INR [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • The proportion of time within the therapeutic INR range [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • The proportion of patients reaching therapeutic INR on days 5 and 8 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • The total number of INR measurements and number of dose adjustments made [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Proportion of INRs > 4 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Major bleeding events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Minor bleeding events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Thromboembolic complications [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 500
Study Start Date: June 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Genotype-guided warfarin dosing
A pharmacogenetic dosing algorithm including clinical factors and genotype information (VKORC1, CYP2C9 and CYP4F2) will be used to determine warfarin doses.
Other: Genotype-guided warfarin dosing
Applying a Pharmacogenetic-guided warfarin dosing algorithm derived from Chinese to determine the daily maintenance dose of warfarin, based on clinical factors (age, sex, body surface area, etc.), and VKORC1, CYP2C9 and CYP4F2 genotypes, to individualize the dosing of warfarin.
Active Comparator: Non-genotype guided warfarin dosing
A fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement.
Other: Non-genotype guided warfarin dosing
A Empiric fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement.

Detailed Description:

Warfarin is the most widely used oral anticoagulation drug for preventing and treating thromboembolic events, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. In 2007, the US Food and Drug Administration updated the label of warfarin, recommending consideration of pharmacogenetic information which has been confirmed to contribute significantly to the variability in warfarin dose requirements. Thereafter, multiple pharmacogenetic dosing algorithms were constructed to predict warfarin dose by integrating clinical and genetic factors. Taken together, approximately between one-third and one- half of the variability in warfarin dose could be explained by the proposed algorithms. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomised settings in Chinese patients.

Study objectives:

  1. To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice in Chinese patients.
  2. To compare the percentage out-of-range (%OOR) International Normalized Ratios (INRs) during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
  3. To compare the cost effectiveness, number of thromboembolic and bleeding events, time within therapeutic INR range, time to reach stable dose and number of supratherapeutic INR peaks during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.

Study design:

This is a prospective, randomized study of Chinese patients who are to initiate chronic warfarin anticoagulation for specific, qualifying clinical reasons (i.e., atrial fibrillation, Deep vein thrombosis/pulmonary embolism, or Prosthetic valve replacement). Qualifying patients will be consented and randomized to an individualized, pharmacogenetic guided warfarin-dosing regimen (PG group) or to standard care (without knowledge of genotype)(STD group). All patients will receive a baseline INR. For patients in PG group, a maintenance dose for each patient will be predicted by the pharmacogenetic algorithm derived previously in Chinese. A maintenance dose of 3 mg/day will designed to each patients in STD group. The starting dose of warfarin that is twice the assigned daily maintenance dose will be prescribed on the first and second days, and then the dose will revert to the assigned maintenance dose.

Study duration:

Each patient will participate for at least 3 months.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients ≥18 years old
  • Patients initiated on warfarin for venous thromboembolism, pulmonary embolism, atrial fibrillation or heart valve replacement that require long- term oral anticoagulation with target INR ranged 1.5-3.0 for at least 3 months
  • Ability to attend scheduled visits
  • Signed informed consent

Exclusion Criteria:

  • Non-eligible subject
  • Pregnant,lactating or of child-bearing potential women
  • Patients with severe co-morbidities (e.g., renal insufficiency/creatinine > 2.5 mg/dL,hepatic insufficiency, active malignancy, terminal disease)
  • Known genotype CYP2C9 or VKORC1 at start of the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01610141

Contacts
Contact: Tong Yin, Dr. 86-13693693085 yintong2000@yahoo.com
Contact: Xiaoqi Li, Dr. 86-15901075996 xiaoqili_2012@126.com

Locations
China
Institute of geriatric Cardiology, General Hospital of People's Liberation Army Recruiting
Beijing, China, 100853
Contact: Tong Yin, Dr.    86-13693693085    yintong2000@yahoo.com   
Contact: Xiaoqi Li, Dr.    86-15901075996    xiaoqili_2012@126.com   
Principal Investigator: Tong Yin, Dr.         
Sponsors and Collaborators
Chinese PLA General Hospital
Investigators
Principal Investigator: Tong Yin, Dr. Institute of Geriatric Cardiology, General Hospital of People's Liberation Army, Beijing China
  More Information

Publications:
Responsible Party: Tong Yin, Institute of Geriatric Cardiology, Chinese PLA General Hospital
ClinicalTrials.gov Identifier: NCT01610141     History of Changes
Other Study ID Numbers: NSFC-30971259
Study First Received: May 30, 2012
Last Updated: October 7, 2013
Health Authority: China: National Natural Science Foundation

Keywords provided by Chinese PLA General Hospital:
pharmacogenetics
warfarin metabolism
CYP2C9
genotyping
VKORC1
CYP4F2
anticoagulation
atrial fibrillation
deep vein thrombosis
pulmonary embolism
Artificial Heart Valve

Additional relevant MeSH terms:
Atrial Fibrillation
Embolism
Heart Valve Diseases
Pulmonary Embolism
Thrombosis
Venous Thrombosis
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 April 17, 2014