Clinical trial NCT02211326: Genotype-guided Warfarin Individualized Treatment
Official title: Pharmacogenetic Algorithm of Response to Warfarin During Initial Anticoagulation in Chinese Elderly Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Deep Venous Thrombosis
Keywords: AF or DVT
Age Over 18 Years, Acquired
Lead sponsor: The Third Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2014-08-07
Enrollment: 660
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: %TTR
timeFrame: 12 weeks
Secondary outcomes:
measure: the time to reach therapeutic INR
timeFrame: 12 weeks
measure: 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
timeFrame: 12 weeks
measure: The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4
timeFrame: 12 weeks
Other outcomes:
measure: the number of additional clinic visits
timeFrame: 12 weeks
Locations:
city: Changsha
country: China
facility: The People's Hospital of Hunan Province
state: Hunan
city: Changsha
country: China
facility: The Central Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The Fourth Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Hospital of Changsha
state: Hunan
city: Changsha
country: China
facility: The Xiangya Hospital of Central South University
state: Hunan
city: Chenzhou
country: China
facility: The First People's Hospital of Chenzhou
state: Hunan
city: Hengyang
country: China
facility: The First Affiliated Hospital of Nanhua university
state: Hunan
city: Hengyang
country: China
facility: The Second Affiliated Hospital of Nanhua university
state: Hunan
city: Loudi
country: China
facility: The Central Hospital of Loudi
state: Hunan
city: Shaoyang
country: China
facility: The Central Hospital of Shaoyang
state: Hunan
city: Shaoyang
country: China
facility: The First People's Hospital of Shaoyang
state: Hunan
city: Xiangtan
country: China
facility: The Central Hospital of Xiangtan
state: Hunan
city: Xiangtan
country: China
facility: The First People's Hospital of Xiangtan
state: Hunan
city: Yiyang
country: China
facility: The Central Hospital of Yiyang
state: Hunan
Study officials:
affiliation: The Third Xiangya Hospital of Central South University
name: GuoPing Yang, professor
role: PRINCIPAL_INVESTIGATOR
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