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Genotype-guided Warfarin Individualized Treatment

Primary Purpose

Atrial Fibrillation, Deep Venous Thrombosis

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Genotype-guided dosing algorithm for warfarin
Standard initiation dose for warfarin
Sponsored by
The Third Xiangya Hospital of Central South University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring AF or DVT, Age Over 18 Years, Acquired

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The People's Hospital of Hunan Province
  • The Central Hospital of Changsha
  • The Fourth Hospital of Changsha
  • The Third Xiangya Hospital of Central South University
  • The Third Hospital of Changsha
  • The Xiangya Hospital of Central South University
  • The First People's Hospital of Chenzhou
  • The First Affiliated Hospital of Nanhua university
  • The Second Affiliated Hospital of Nanhua university
  • The Central Hospital of Loudi
  • The Central Hospital of Shaoyang
  • The First People's Hospital of Shaoyang
  • The Central Hospital of Xiangtan
  • The First People's Hospital of Xiangtan
  • The Central Hospital of Yiyang

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

genotype-guided group

control group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

%TTR
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

Secondary Outcome Measures

the time to reach therapeutic INR
the time to reach therapeutic INR
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
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
The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4

Full Information

First Posted
August 6, 2014
Last Updated
November 1, 2017
Sponsor
The Third Xiangya Hospital of Central South University
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1. Study Identification

Unique Protocol Identification Number
NCT02211326
Brief Title
Genotype-guided Warfarin Individualized Treatment
Official Title
Pharmacogenetic Algorithm of Response to Warfarin During Initial Anticoagulation in Chinese Elderly Patients
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 1, 2014 (Actual)
Primary Completion Date
January 16, 2017 (Actual)
Study Completion Date
May 1, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Third Xiangya Hospital of Central South University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Deep Venous Thrombosis
Keywords
AF or DVT, Age Over 18 Years, Acquired

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
660 (Actual)

8. Arms, Groups, and Interventions

Arm Title
genotype-guided group
Arm Type
Experimental
Arm Description
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.
Arm Title
control group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Genotype-guided dosing algorithm for warfarin
Intervention Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Standard initiation dose for warfarin
Intervention Description
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.
Primary Outcome Measure Information:
Title
%TTR
Description
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
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
the time to reach therapeutic INR
Description
the time to reach therapeutic INR
Time Frame
12 weeks
Title
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
Description
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
Title
The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
Description
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
Other Pre-specified Outcome Measures:
Title
the number of additional clinic visits
Description
the number of additional clinic visits
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GuoPing Yang, professor
Organizational Affiliation
The Third Xiangya Hospital of Central South University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The People's Hospital of Hunan Province
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410002
Country
China
Facility Name
The Central Hospital of Changsha
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410004
Country
China
Facility Name
The Fourth Hospital of Changsha
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410006
Country
China
Facility Name
The Third Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
The Third Hospital of Changsha
City
Changsha
State/Province
Hunan
Country
China
Facility Name
The Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
Country
China
Facility Name
The First People's Hospital of Chenzhou
City
Chenzhou
State/Province
Hunan
ZIP/Postal Code
423000
Country
China
Facility Name
The First Affiliated Hospital of Nanhua university
City
Hengyang
State/Province
Hunan
Country
China
Facility Name
The Second Affiliated Hospital of Nanhua university
City
Hengyang
State/Province
Hunan
Country
China
Facility Name
The Central Hospital of Loudi
City
Loudi
State/Province
Hunan
ZIP/Postal Code
417000
Country
China
Facility Name
The Central Hospital of Shaoyang
City
Shaoyang
State/Province
Hunan
ZIP/Postal Code
422000
Country
China
Facility Name
The First People's Hospital of Shaoyang
City
Shaoyang
State/Province
Hunan
ZIP/Postal Code
422001
Country
China
Facility Name
The Central Hospital of Xiangtan
City
Xiangtan
State/Province
Hunan
ZIP/Postal Code
411100
Country
China
Facility Name
The First People's Hospital of Xiangtan
City
Xiangtan
State/Province
Hunan
ZIP/Postal Code
411101
Country
China
Facility Name
The Central Hospital of Yiyang
City
Yiyang
State/Province
Hunan
ZIP/Postal Code
413000
Country
China

12. IPD Sharing Statement

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Genotype-guided Warfarin Individualized Treatment

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