Genotype-guided Versus Standard for Warfarin Dosing

Randomized Trial of Genotype-guided Versus Standard for Warfarin Dosing

To compare the efficiency and safety between gene-oriented group and standard care group during 90 days of initial warfarin-treatment for requiring anticoagulation patients with valve replacement or atrial fibrillation with or without valvular heart disease。

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Valvular Heart Disease
• Intervention / Treatment: Other: Gene-directed dosage of warfarin; Other: standard dosage of warfarin

Detailed Description

Due to narrow therapeutic window, and individual differences in dosage, inappropriate use of warfarin may lead to serious complications and ineffective. Based on the results of the research on the transformation of warfarin pharmacogenomics, this study investigates the clinical application of gene-directed warfarin dose prediction model through the preset dosage regimen of warfarin during the initial treatment phase. Compared with the conventional treatment, that is to say empirical medication, this study is to verify the feasibility and value of gene-oriented warfarin dose prediction model, in order to establish a practical guidance to optimize the rational use of warfarin treatment program, to enable patients to obtain effective, safe warfarin dose, and to achieve the established anticoagulant strength faster and safer, as the same time, to reduce the times of patients was blood and the incidence of bleeding/embolism, and to save costs and ensure the safety of warfarin clinical medication.

• Study Type: Interventional
• Enrollment (Actual): 560
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100037
      • Chinese Academy of Medical Sciences Fuwai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged from 18 to 70 years old, requiring anticoagulation because of valvular or non-valvular atrial fibrillation or after valvular replacement. Patients could visit to be followed up in our hospital clinic regularly and agree to participate in the clinical trial and sign a written informed consent.

Exclusion Criteria:

• Patients will be excluded from the trial if aged <18 years old or > 75 years old, pregnant and lactating, if treated tricuspid valve replacement, or coronary artery bypass grafting before, if diagnosed with congenital heart disease, if known their CYP2C9 or VKORC1 genotype, if taken dicoumarol drugs previously or taking them now, if not suitable for enrollment judged by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gene-directed group; the first day given model prediction dose * 1.5 times（<6mg）；the second day given model prediction dose；adjusted dose based on INR from the third day	Other: Gene-directed dosage of warfarin; the first day given model prediction dose * 1.5 times（<6mg）；the second day given model prediction dose；adjusted dose based on INR from the third day
Active Comparator: Standard care group; the first day given 4.5mg; adjusted dose based on INR from the second day	Other: standard dosage of warfarin; the first day given 4.5mg; adjusted dose based on INR from the second day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
therapeutic INR range (TTR) 90	The percentage of time in therapeutic INR range (TTR) using the number of INRs within the therapeutic range divided by the number of INRs collected, will be assessed at Day90, and the TTR of all patients will be reported.	at Day90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
therapeutic INR range (TTR) 28	The percentage of time in therapeutic INR range (TTR) using the number of INRs within the therapeutic range divided by the number of INRs collected, will be assessed at Day28, and the TTR of all patients will be reported.	at Day28
Time of the first time of the target INR	Time of the first time for participants to reach the target INR will be collected and reported during the study.	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
thrombus or embolism or bleeding complications	The number of thrombus or embolism or any hemorrhage events for participants through the study completion will be collected and assessed at Day90.	90 days

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Investigators: Principal Investigator: Lu Hua, MD. PhD, Thrombosis and Vascular Medicine Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: February 27, 2018
• First Submitted That Met QC Criteria: March 25, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: warfarin; gene
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Atrial Fibrillation; Heart Valve Diseases; Anticoagulants; Warfarin
• Other Study ID Numbers: Z171100001017216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Consent for sharing of non identifiable study data for regulatory authorities.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No