Effect of CYP2C9 and VKORC1 genotype on inter-individual warfarin dose - A prospective study in Chinese population

ISRCTN	ISRCTN54178709
DOI	https://doi.org/10.1186/ISRCTN54178709
Protocol serial number	N/A
Sponsor	National Natural Science Foundation of China
Funder	National Natural Science Foundation of China (National Science Fund for Distinguished Young Scholars; ref: 30325037)

Submission date: 06/06/2007
Registration date: 26/07/2007
Last edited: 10/06/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Xiang-Min Xu
Scientific

Technology Centre of Prenatal Diagnosis and Genetic Testing
Nanfang Hospital
Tonghe
Guangzhou
Guangdong
510515
China

Phone	+86 20 61648293
Email	gzxuxm@pub.guangzhou.gd.cn

Study information

Primary study design	Interventional
Study design	Randomised controlled trial.
Secondary study design	Randomised controlled trial
Scientific title	Effect of CYP2C9 and VKORC1 genotype on inter-individual warfarin dose - A prospective study in Chinese population
Study objectives	The large inter-individual variation in the requirement for warfarin is mainly result from patients genetic background, especially polymorphisms in CYP2C9 and VKORC1 genes. Here we are going to use a computational algorithm, which is validated through retrospective data, to predict the stable dose to a given patient. Our algorithm is comprised of not only physical data of the patient, but also their genetic polymorphisms.
Ethics approval(s)	Approval received from the Nan Fang Hospital Medical Ethics Committee on the 25th April 2007 (ref: 200706)
Health condition(s) or problem(s) studied	Not applicable
Intervention	1. Retrospective study We enrolled 200 patients undergoing stable warfarin anticoagulation therapy. An algorithm has been established based on patients personal data including gender, age, height, weight and genotypes of CYP2C9 and VKORC1. 2. Prospective study Treatment group: Patients stable dose will be calculated using the algorithm before they use warfarin. The first three warfarin doses will be taken according to the calculated dose. Then the doses will be adjusted depending on INR values until target INR (2.0-3.0) is obtained. Control group: Patients use the current method to find warfarin stable dose.
Intervention type	Other
Primary outcome measure(s)	1. Difference in stable warfarin doses among patients with genotypes CYP2C9 and VKORC1 2. An algorithm of stable warfarin dose established using multiple linear-regression equation 3. To assess the feasibility of the algorithm for treatment group compared to control group on: 3.1. Days until a stable therapeutic INR (2.0-3.0) 3.2. Days until an adverse outcome
Key secondary outcome measure(s)	1. INR, measured every day during hospitalization and twice a week after discharge 2. Warfarin dose, recorded every day 3. Adverse outcome, recorded every day
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	400
Total final enrolment	422
Key inclusion criteria	1. Patients who will initiate warfarin administration 2. Aged 18 years or more 3. Written informed consent to participate in the study
Key exclusion criteria	1. Patients with previous and current liver disease 2. Renal failure (creatinine greater than 106 μmo/L) 3. Base coagulant response time (INR) is 1.4 or more 4. Patients using any other known drugs that related to CYP2C9 5. Use of warfarin in the past three months
Date of first enrolment	01/06/2006
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

China

Study participating centre

Technology Centre of Prenatal Diagnosis and Genetic Testing

Guangdong
510515
China

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/03/2009	10/06/2021	Yes	No

Editorial Notes

10/06/2021: Publication reference and total final enrolment added.