A Randomized, Multi-Center, Double-Blind Clinical Trial to Evaluate the Use of Clinical Plus Genetic Information to Guide Warfarin Therapy Initiation and Improve Anticoagulation Control for Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,015
- 试验地点
- 35
- 主要终点
- Percentage of time participants spend within the therapeutic INR range (PTTR)
研究概览
简要总结
Individuals taking warfarin often need frequent dose changes as the international normalized ratio (INR) gets too high or too low which could result in a higher risk of thromboembolism, bleeding and early discontinuation of a highly useful therapy. This study will compare two approaches to warfarin dosing to examine the utility of using genetic information for warfarin dosing.
详细描述
The objective of the Clarification of Optimal Anticoagulation through Genetics (COAG) trial is to conduct a 1,022 participant, multicenter, double-blind, randomized trial comparing two approaches to guiding warfarin therapy initiation: 1) initiation of warfarin therapy based on algorithms using clinical information and an individual's genotype using genes known to influence warfarin response ("genotype-guided dosing"), and 2) initiation of warfarin therapy based on algorithms using only clinical information ("clinical-guided dosing"). The study hypothesis is that the use of genetic and clinical information for selecting the dose of warfarin during the initial dosing period will lead to improvement in stability of anticoagulation(AC) relative to a strategy that incorporates only clinical information (without genetics) for initial dosing. Each study arm will include a baseline dose initiation algorithm and a dose revision algorithm applied over the first 4 to 5 doses of warfarin therapy. By comparing the two strategies in this trial, the study will be able to determine if genetic information provides added benefit above and beyond what can be gleaned simply with clinical information. This study is a proof-of-concept efficacy trial. Efficacy is defined as a measure of whether, under optimal application, dosing algorithms will lead to improvement in care. The trial will thus answer the question: "can the use of clinical plus genetic information lead to an improvement in anticoagulation control above and beyond the use of only clinical information during the initiation of warfarin, when applied in a uniform and optimal manner to all patients?" Because efficacy has not yet been established for genotype-guided dosing of warfarin, it is important to first test whether this approach can, indeed, improve anticoagulation outcomes under controlled conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness and ability to sign informed consent
- •Able to be followed in outpatient AC clinic
- •Expected duration of warfarin therapy of at least 1 month
- •AC management for the patient will be performed in-hospital and as an outpatient by clinicians that will adhere to the study dosing algorithms and dose titration plans
- •Target INR 2-3
排除标准
- •Currently taking warfarin
- •Prior warfarin therapy with known required stable dose
- •Clinician opinion that warfarin dosing needs to be adjusted for reasons not accounted for by dosing algorithm
- •Abnormal baseline INR (off warfarin) (e.g., due to liver disease, antiphospholipid antibody)
- •Contraindication to warfarin treatment for at least 3 months
- •Life expectancy of less than 1 year
- •Pregnant women or child-bearing women not using medically approved method of birth control (requires negative pregnancy test to exclude pregnancy in child-bearing women)
- •Inability to follow-up on a regular basis with anticoagulation practitioners participating in the trial
- •Any factors likely to limit adherence to warfarin
- •Cognitive or other causes of inability to provide informed consent or follow study procedures
- •Participating in another trial that prohibits participation in the COAG trial or planned enrollment in such a trial within the first 6 months of warfarin therapy
- •Estimated blood loss of more than 1,000 cc requiring blood transfusions within 48 hours prior to randomization
- •Genotype (CYP2C9 or VKORC1) known to participant from prior testing
结局指标
主要结局
Percentage of time participants spend within the therapeutic INR range (PTTR)
时间窗: Measured during the first 4 weeks of therapy
次要结局
- Occurrence of INR greater than 4 or serious clinical event(Measured during the first 4 weeks)