Atrial Fibrillation, Deep Venous Thrombosis
Conditions
Keywords
AF or DVT, Age Over 18 Years, Acquired
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.
Interventions
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.
BEHAVIORALStandard 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.
Sponsors
The Third Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| %TTR | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the time to reach therapeutic INR | 12 weeks | 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 | 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 |
| 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 | The number of adjustment units in the dose of warfarin (with 0.375 mg (1/8 tablet) as a unit); Incidence of INR ≥ 4 |
Other
| Measure | Time frame | Description |
|---|---|---|
| the number of additional clinic visits | 12 weeks | the number of additional clinic visits |
Countries
China
Outcome results
None listed