Genotype-guided Warfarin Individualized Treatment

November 1, 2017 updated by: The Third Xiangya Hospital of Central South University

Pharmacogenetic Algorithm of Response to Warfarin During Initial Anticoagulation in Chinese Elderly Patients

The purpose of this study is to determine whether the international pharmacogenetic algorithm is better than the standard initiation dosing and whether the two algorithms are suitable for Chinese elderly patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study protocol is a multicenter, randomized, patient-blinded and controlled trial, comparing two approaches among 864 enrolled AF(atrial fibrillation) or DVT(deep venous thrombosis) patients for guiding warfarin initial anticoagulation in Chinese elderly patients: the intervention group using the algorithm of International Warfarin Pharmacogenetic Consortium and its dose revision, and the control group using a standard initiation dose (2.25 mg).The study hypothesis is that the intervention group relative to the control group will increase the percentage of time in therapeutic INR (international normalized ratio) range during the first 3 months.This trial is the first prospective large-scale randomized controlled trial for elders in China. It is of great significance for promoting special crowd individualization of anticoagulants at home and abroad.

Study Type

Interventional

Enrollment (Actual)

660

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
    • Hunan
      • Changsha, Hunan, China, 410013
        • The Third Xiangya Hospital of Central South University
      • Changsha, Hunan, China, 410002
        • The People's Hospital of Hunan Province
      • Changsha, Hunan, China, 410004
        • the central hospital of Changsha
      • Changsha, Hunan, China, 410006
        • The Fourth Hospital of Changsha
      • Changsha, Hunan, China
        • The Third Hospital of Changsha
      • Changsha, Hunan, China
        • The Xiangya Hospital of Central South University
      • Chenzhou, Hunan, China, 423000
        • The First People's Hospital of Chenzhou
      • Hengyang, Hunan, China
        • The First Affiliated Hospital of Nanhua University
      • Hengyang, Hunan, China
        • The Second Affiliated Hospital of Nanhua University
      • Loudi, Hunan, China, 417000
        • The Central Hospital of Loudi
      • Shaoyang, Hunan, China, 422000
        • The Central Hospital of Shaoyang
      • Shaoyang, Hunan, China, 422001
        • The First People's Hospital of Shaoyang
      • Xiangtan, Hunan, China, 411100
        • The Central Hospital of Xiangtan
      • Xiangtan, Hunan, China, 411101
        • The First People's Hospital of Xiangtan
      • Yiyang, Hunan, China, 413000
        • The Central Hospital of Yiyang

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria：1) Chinese male or female aged ≥18 years; 2) Requiring at least 12-week warfarin therapy as judged by clinicians; 3) Subjects with DVT/AF and a post-therapy target INR of 1.5-2.5; 4) Capable of providing written informed consent; 5) Capable of maintaining excellent communications with investigators and completing trial in accordance with trial stipulations.

Exclusion criteria：1) Subjects previously taking warfarin; 2) Known genotypes of CYP2C9 or/and VKORC1; 3) Subjects receiving or expecting to receive other therapies or other anticoagulants; 4) Subjects with contraindications for warfarin; 5) Subjects with severe cognitive dysfunctions; 6) Baseline INR ≥1.5; 7) Subjects with drug or alcohol dependence within the last 12 months; 8) Subjects receiving blood transfusion or bone marrow transplantation within the last 2 weeks; 9) Planning to receive invasive examinations (except for standard endoscopy) with a hemorrhagic tendency or undergoing surgery during trial.10) Prior to randomization, subjects receiving any trial drug or device within the last 3 months or planning to receive such an investigational therapy during trial; 11) Subjects with the following diagnoses or conditions: active malignant carcinomas (diagnosed within the last 5 years), but excluding adequately-treated non-melanoma skin cancer or other non-invasive or in situ cancer (e.g. cervical cancer in situ); anti-neoplastic therapy within the last 5 years (medication, radiotherapy or/and surgery); overt active disease or infection; life expectancy <6 months; 12）Other clinical reasons for unsuitable recruitment as judged by clinicians.

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: genotype-guided group
Interventions：on day1~day3, patients received dose according to IWPC formula (PGx-1) included clinical variables and genotype data for VKORC1, CYP2C9*1, CYP2C9*2, and CYP2C9*3; on day4~day7, patients received dose according to Lenzini formula consisted of clinical variables, VKORC1, CYP2C9*2, CYP2C9*3 and previous INR and dosing information (PGx-2); and on day8, the clinicians adjusted the dose according to observed INR.The overall follow-up period is 12 weeks.
Behavioral: Genotype-guided dosing algorithm for warfarin
Intervention：initial dosing of warfarin for the first 3 days of treatment will be determined by IWPC( International Warfarin Pharmacogenetics Consortium) algorithm (PG-1),a second dose adjustment will be made after 3 doses of warfarin using a dose revision algorithm (PG-2) that combined INR values,the dose will be adjusted depending on the measurements of INR values after 7 days.The overall follow-up period is 12 weeks.
Active Comparator: control group
Interventions：on day1~day3, patients were given initial dose (2.25mg); and starting from day4, the clinicians began to adjust the dose for patients according to observed INR.The overall follow-up period is 12 weeks.
Behavioral: Standard initiation dose for warfarin
Intervention：initial dosing of warfarin for the first 3 days of treatment will be determined by standard initiation dose. Following this initiation dose of warfarin,the dose will be adjusted depending on the measurements of INR values after 3 days.The overall follow-up period is 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
%TTR
Time Frame: 12 weeks
percentage of time in the therapeutic INR (%TTR) of INR 2-3 (<60 years old) or 1.5-2.5 (≥ 60 years old) within 12 weeks
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the time to reach therapeutic INR
Time Frame: 12 weeks
the time to reach therapeutic INR
12 weeks
the time to reach stable warfarin dose which defined as the dose to achieve INR within ±0.1 of therapeutic range at Day 8 post-dose
Time Frame: 12 weeks
the time to reach stable warfarin dose which defined as the dose to achieve INR within ±0.1 of therapeutic range at Day 8 post-dose
12 weeks
The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
Time Frame: 12 weeks
The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
the number of additional clinic visits
Time Frame: 12 weeks
the number of additional clinic visits
12 weeks

Collaborators and Investigators

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

Sponsor

The Third Xiangya Hospital of Central South University

Investigators

  • Principal Investigator: GuoPing Yang, professor, The Third Xiangya Hospital of Central South 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 (Actual)

September 1, 2014

Primary Completion (Actual)

January 16, 2017

Study Completion (Actual)

May 1, 2017

Study Registration Dates

First Submitted

August 6, 2014

First Submitted That Met QC Criteria

August 6, 2014

First Posted (Estimate)

August 7, 2014

Study Record Updates

Last Update Posted (Actual)

November 6, 2017

Last Update Submitted That Met QC Criteria

November 1, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XY3-WARF1405A01
  • ChiCTR-TRC-14004757 (Registry Identifier: Chinese Clinical Trial Registry)

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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