Therapeutic Equivalence Between Branded and Generic Warfarin Sodium Tablets in Adult Patients With Atrial Fibrillation in Brazil - Crossover Randomized Controlled Equivalence Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Difference between Delta INR
研究概览
简要总结
The purpose of this study is to assess whether the switch from branded to generic warfarin or between different generic warfarin tablets may cause fluctuation in the results of coagulation tests (International Normalized Rate, acronym INR) in patients, thus predisposing them to unnecessary risks.
详细描述
[Changes to the protocol made until the stage of the statistical analysis plan, before data analysis and also before unblinding.]
- Objective
1.1 Main Objective
We aim to determine, through mean INR difference between formulations, whether there is therapeutic equivalency between the branded warfarin sodium (Marevan®) and the generic formulations in atrial fibrillation patients in Brazil.
1.2 Specific Objective
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
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
- •diagnosis of nonvalvular atrial fibrillation atrial flutter by electrocardiogram and echocardiography;
- •CHA2DS2VASc score equal to or greater than 1;
- •already in use of warfarin for at least 2 months;
- •during the run-in, at least one of the three (including the baseline) INR results within 2.0 and 3.0 and a difference of INR results at the 3th and 4th week ≤ ±0.8
- •signing of Informed Consent Form.
排除标准
- •patients with serious contraindications to the use of anticoagulants (significant bleeding, known sensitivity to warfarin);
- •women of childbearing age, pregnant or breastfeeding;
- •patients with thrombocytopenia;
- •patients with hepatic or renal impairment;
- •patients with a history of bleeding episodes due to congenital deficiency of coagulation factors;
- •patients enrolled in another trial;
- •patients initiating treatment with drugs with major interactions or which are contraindicated when used concomitantly with warfarin, according to our list (Annex I).
研究组 & 干预措施
Sequence A
Phase 1 (run-in): Marevan®
Phase 2: Marevan®
Phase 3: generic warfarin #1
Phase 4: generic warfarin #2
干预措施: Marevan® (Drug)
Sequence A
Phase 1 (run-in): Marevan®
Phase 2: Marevan®
Phase 3: generic warfarin #1
Phase 4: generic warfarin #2
干预措施: generic warfarin #1 (Drug)
Sequence A
Phase 1 (run-in): Marevan®
Phase 2: Marevan®
Phase 3: generic warfarin #1
Phase 4: generic warfarin #2
干预措施: generic warfarin #2 (Drug)
Sequence B
Phase 1 (run-in): generic warfarin #1
Phase 2: generic warfarin #1
Phase 3: Marevan®
Phase 4: generic warfarin #2
干预措施: Marevan® (Drug)
Sequence B
Phase 1 (run-in): generic warfarin #1
Phase 2: generic warfarin #1
Phase 3: Marevan®
Phase 4: generic warfarin #2
干预措施: generic warfarin #1 (Drug)
Sequence B
Phase 1 (run-in): generic warfarin #1
Phase 2: generic warfarin #1
Phase 3: Marevan®
Phase 4: generic warfarin #2
干预措施: generic warfarin #2 (Drug)
Sequence C
Phase 1 (run-in): generic warfarin #1
Phase 2: generic warfarin #1
Phase 3: generic warfarin #2
Phase 4: Marevan®
干预措施: Marevan® (Drug)
Sequence C
Phase 1 (run-in): generic warfarin #1
Phase 2: generic warfarin #1
Phase 3: generic warfarin #2
Phase 4: Marevan®
干预措施: generic warfarin #1 (Drug)
Sequence C
Phase 1 (run-in): generic warfarin #1
Phase 2: generic warfarin #1
Phase 3: generic warfarin #2
Phase 4: Marevan®
干预措施: generic warfarin #2 (Drug)
Sequence D
Phase 1 (run-in): Marevan®
Phase 2: Marevan®
Phase 3: generic warfarin #2
Phase 4: generic warfarin #1
干预措施: Marevan® (Drug)
Sequence D
Phase 1 (run-in): Marevan®
Phase 2: Marevan®
Phase 3: generic warfarin #2
Phase 4: generic warfarin #1
干预措施: generic warfarin #1 (Drug)
Sequence D
Phase 1 (run-in): Marevan®
Phase 2: Marevan®
Phase 3: generic warfarin #2
Phase 4: generic warfarin #1
干预措施: generic warfarin #2 (Drug)
Sequence E
Phase 1 (run-in): generic warfarin #2
Phase 2: generic warfarin #2
Phase 3: Marevan®
Phase 4: generic warfarin #1
干预措施: Marevan® (Drug)
Sequence E
Phase 1 (run-in): generic warfarin #2
Phase 2: generic warfarin #2
Phase 3: Marevan®
Phase 4: generic warfarin #1
干预措施: generic warfarin #1 (Drug)
Sequence E
Phase 1 (run-in): generic warfarin #2
Phase 2: generic warfarin #2
Phase 3: Marevan®
Phase 4: generic warfarin #1
干预措施: generic warfarin #2 (Drug)
Sequence F
Phase 1 (run-in): generic warfarin #2
Phase 2: generic warfarin #2
Phase 3: generic warfarin #1
Phase 4: Marevan®
干预措施: generic warfarin #2 (Drug)
Sequence F
Phase 1 (run-in): generic warfarin #2
Phase 2: generic warfarin #2
Phase 3: generic warfarin #1
Phase 4: Marevan®
干预措施: Marevan® (Drug)
Sequence F
Phase 1 (run-in): generic warfarin #2
Phase 2: generic warfarin #2
Phase 3: generic warfarin #1
Phase 4: Marevan®
干预措施: generic warfarin #1 (Drug)
结局指标
主要结局
Difference between Delta INR
时间窗: At the fourth week of each period
INR: International normalized ratio. INR will be assessed twice a month during the 16 weeks of study. Delta INR will be calculated by the difference, in absolute numbers (i.e. in module), between the two valid INR measurements due for each patient with each formulation at each period. Difference between the delta INRs will be the outcome. We will compare generic to branded warfarin (Marevan®) and the generic formulations to each other.
次要结局
- Difference in warfarin dosage needed(At the fourth week of each period)
- Time in therapeutic range (TTR)(At the fourth week of each period)
- Difference between mean INR(At the fourth week of each period)
- Incidence of thromboembolic events(At the fourth week of each period)
- Incidence of bleeding events(At the fourth week of each period)
研究者
Carolina Gomes Freitas
Graduate student (PhD)
Federal University of São Paulo