Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes

January 13, 2019 updated by: Liang-Wan Chen MD, Fujian Medical University

Individualized Administration of Warfarin by Polymorphisms of VKORC1 and CYP2C9 Genes:A Randomized Controlled Trial, Multi-center Trial

The purpose of this study is to explore the individualized administration model of warfarin suitable for Chinese people, and provide a scientific reference for the use of warfarin to Chinese people.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

About 600 patients with VKORC1 and CYP2C9 gene mutations were included in the treatment of warfarin anticoagulant therapy. The main indications include valve replacement, atrial fibrillation, pulmonary embolism, etc., randomly divided into 2 groups, respectively, the control group (that is, the use of fixed-dose group), Bayesian-model group, the use of single-blind treatment method, to evaluate the number of major adverse events, TTR and INR adjustments in patients between different groups after three months of taking warfarin, and then to explore the individualized drug use model of warfarin suitable for Chinese population.

In the Bayesian group, according to the genotype of VKORC1 and CYP2C9, the stable dose was calculated by the dose prediction model of Bayesian, and the first three drugs were taken at this dose, and then adjusted to the actual stable dose according to the change of INR. Meanwhile, the control group was administered according to the traditional way, that is, the initial dose is 2.5 or 3mg/d and is gradually adjusted to a stable dose according to changes of INR. The monitoring frequency of INR is: once a day from the beginning of the drug to the time of discharge, once a week after discharge, and once a month after the stable dose is obtained. Detailed records of the number of days to reach a stable dose, the INR value and the occurrence of side effects and time are documented. The concrete steps are as follows:

  1. clinicians to judge the standard of the selection criteria;
  2. to obtain the consent of the patient and sign an informed consent certificate;
  3. to collect 2ml anticoagulant blood before the drug, fill in the application form for individualized drug use in warfarin, and indicate the experimental group and control group;
  4. the specimen assigned to the laboratory for Genotyping;
  5. lab to calculate the predicted stable warfarin dose and the results fed back to the clinician within one working day after receiving the specimen;
  6. in the control group, the drug retained at the regular dose, and the first 3 days of the experimental group administered at the predicted dose;
  7. the dosage of warfarin in the two groups of cases adjusted to the stable dose according to the value, and the adjustment amplitude of the experimental group also referred to the predicted stable dose.
  8. to monitor INR once a day during hospitalization, and to those who do not receive a stable dose of discharge, follow up and monitor INR once a week until a stable dose or medication is obtained for 90 days;
  9. to document clinical trial records, including the daily use of warfarin, each detection of the appearance of the situation like INR value, bleeding, venous embolism and other side effects.

Finally，according to the outcome parameters,statistical analysis were performed with SPSS 11.5 software. A value of P < 0.05 was considered statistically significant.

Study Type

Interventional

Enrollment (Anticipated)

600

Phase

  • Not Applicable

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

  • China
    • Fujian
      • FuZhou, Fujian, China, 350001
        • Recruiting
        • the Department of Cardiovascular Surgery
        • Contact:
        • Contact:

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

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age > 14 years old；
  2. Warfarin anticoagulant therapy is required for at least 3 months；
  3. The genotype of patient VKORC1 is non-AA, CYP2C9 genotype is non*1/*1； the patients who are followed up, regularly monitored for INR and willing to provide peripheral blood for DNA extraction and genetic testing；
  4. The patient or family members can understand the research plan and will participate in this study and provide a written informed consent；

Exclusion Criteria:

  1. Severe liver dysfunction (ChildPugh ≥ 10);
  2. Severe infection, respiratory failure;
  3. Severe heart failure ( NYHA ≥ IV);
  4. Severe renal insufficiency (Ccr ≤ 20ml / min);
  5. Cancer;
  6. Diseases of the blood system;
  7. Severe pulmonary hypertension (PAPm ≥ 45mmHg);
  8. Abnormal thyroid function;
  9. Patients with a history of venous thromboembolism, or serious events such as severe bleeding or embolism;
  10. Women who are pregnant or breastfeeding;
  11. Taking or planning to take other oral anticoagulants;
  12. The base INR value is >1.4;
  13. VKORC1, CYP2C9 genotypes are AA, *1/*1;
  14. Secondary valve replacement surgery;
  15. Emergency hospital admission for valve surgery;
  16. Diagnosis of coronary atherosclerotic heart disease;
  17. Severe mental illness, mental disorder ; -

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: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard anticoagulant group
Experimental: Bayesian model group
Other: dose regime
The initial dose of the experimental group will be calculated by the Bayesian model.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
excessive anticoagulant time ratio
Time Frame: 3 months postoperatively
INR>3，INR>4
3 months postoperatively
The occurrence of primary bleeding events
Time Frame: 3 months postoperatively
gastrointestinal hemorrhage, intracerebral hemorrhage,etc
3 months postoperatively
The occurance of secondary bleeding events
Time Frame: 3 months postoperatively
nasal bleeding, skin stasis,etc
3 months postoperatively
The occurrence of thrombosis events
Time Frame: 3 months postoperatively
ischemic stroke, deep vein thrombosis,etc
3 months postoperatively

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of time in therapeutic range
Time Frame: 3 months, 6 months, 12 months postoperatively
3 months, 6 months, 12 months postoperatively
The time required to reach the treatment target INR for the first time;
Time Frame: 3 months postoperatively
3 months postoperatively
The time required from the beginning of treatment to the stable dose;
Time Frame: 3 months postoperatively
3 months postoperatively
The percentage of time below the target INR range;
Time Frame: 3 months postoperatively
3 months postoperatively
The percentage of time above the target INR range;
Time Frame: 3 months postoperatively
3 months postoperatively
The number of dose adjustments and the number of INR measured during the first month of treatment;
Time Frame: 3 months postoperatively
3 months postoperatively
The proportion of patients in each group receiving a stable dose after follow-up;
Time Frame: 3 months postoperatively
3 months postoperatively
The proportion of patients in each group having side effects after follow-up
Time Frame: 3 months postoperatively
3 months postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fujian Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Anticipated)

February 1, 2019

Primary Completion (Anticipated)

January 1, 2022

Study Completion (Anticipated)

January 1, 2023

Study Registration Dates

First Submitted

January 6, 2019

First Submitted That Met QC Criteria

January 6, 2019

First Posted (Actual)

January 9, 2019

Study Record Updates

Last Update Posted (Actual)

January 15, 2019

Last Update Submitted That Met QC Criteria

January 13, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CLW2018WA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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