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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT01610141
Other study ID # NSFC-30971259
Secondary ID
Status Recruiting
Phase Phase 4
First received May 30, 2012
Last updated October 7, 2013
Start date June 2012
Est. completion date June 2015

Study information

Verified date October 2013
Source Chinese PLA General Hospital
Contact Tong Yin, Dr.
Phone 86-13693693085
Email yintong2000@yahoo.com
Is FDA regulated No
Health authority China: National Natural Science Foundation
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 500
Est. completion date June 2015
Est. primary completion date June 2014
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 80 Years
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

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.
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.

Locations

Country Name City State
China Institute of geriatric Cardiology, General Hospital of People's Liberation Army Beijing

Sponsors (1)

Lead Sponsor Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

Liu Y, Yang J, Xu Q, Xu B, Gao L, Zhang Y, Zhang Y, Wang H, Lu C, Zhao Y, Yin T. Comparative performance of warfarin pharmacogenetic algorithms in Chinese patients. Thromb Res. 2012 Sep;130(3):435-40. doi: 10.1016/j.thromres.2012.02.003. Epub 2012 Feb 27. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary A comparison between the pharmacogenetic and standard arms of the per-patient percentage of out-of-range INRs (<1.5, >3). 3 months Yes
Secondary Time to the first supratherapeutic INR 3 months Yes
Secondary The proportion of time within the therapeutic INR range 3 months No
Secondary The proportion of patients reaching therapeutic INR on days 5 and 8 3 months No
Secondary The total number of INR measurements and number of dose adjustments made 3 months No
Secondary Proportion of INRs > 4 3 months Yes
Secondary Major bleeding events 3 months Yes
Secondary Minor bleeding events 3 months Yes
Secondary Thromboembolic complications 3 months Yes
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