A phase 3, randomized, double-blind, double-dummy, parallel-group, multi-center, multi-national study for the evaluation of efficacy and safety of (LMW) heparin/edoxaban versus (LMW) heparin/warfarin in subjects with symptomatic deep-vein thrombosis and/or pulmonary embolism.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 7,500
- 试验地点
- 36
- 主要终点
- - Symptomatic recurrent VTE, i.e., the composite of DVT, non-fatal PE, and fatal PE
研究概览
简要总结
This is a Phase 3, multi-national, multi-center, randomized, double-blind, matching placebo, parallel-group (2 treatment groups), non-inferiority study for efficacy. The maximum treatment period for any individual subject after randomization will be 12 months. While 12 months of treatment are planned, mitigating factors related to the subject?s clinical status will likely influence the total duration of treatment a given subject actually receives. Nevertheless, it is planned that all subjects will be administered a minimum of three months treatment consistent with current American College of Chest Physicians (ACCP) Guidelines. It is anticipated that approximately 10% of subjects will discontinue treatment after 3 months, an additional 40% will discontinue after 6 months, and 50% will complete the entire 12 months of treatment. Treatment durations will be monitored during the study, and the Steering Management Coordinating Committee (SMCC) will take appropriate action to ensure that an approximate proportion of subjects complete the treatment durations as indicated. Regardless of the total duration of study drug treatment actually received, efficacy and safety data will be collected on all subjects, including those who temporarily interrupt or permanently discontinue study drug, during the entire 12-month period following randomization. For all subjects, contacts (visits or phone calls) are scheduled at regular time points. During these contacts, the treatment and clinical course of the subject will be evaluated. Subjects with suspected efficacy or safety endpoints will undergo confirmatory testing. All subjects, including those who temporarily interrupt or permanently discontinue study drug, will be expected to have the following: - A Month 12 visit which is critical for the modified intent to treat (mITT) analysis of efficacy, - A safety follow-up visit approximately 1 month after the last dose of study drug. In this context, last dose means last dose before permanent study drug discontinuation (premature or at the scheduled end of treatment). Globally approximately 7,500 subjects will be randomized and in India 1000 subjects are targeted to be enrolled. The date of first patient enrollment in India is May 15, 2010.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified block randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
入选标准
- •Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Accepts Healthy Volunteers: No 1)Male or female subjects older than the minimum legal adult age (country specific); 2)Acute symptomatic proximal DVT and/or symptomatic PE confirmed at the site by appropriate diagnostic imaging; 3)Able to provide written informed consent.
排除标准
- •Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current episode of DVT and/or PE; 2)More than 48 hours pre-treatment with anticoagulant therapy prior to randomization; 3)Calculated CrCL < 30 mL/min; 4)significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis) or alanine transaminase (ALT) >= 2 times the upper limit of normal (ULN), or total bilirubin (TBL) x 1.5 times the ULN; 5)patients with active cancer for whom long term treatment with (LMW) heparin is anticipated; 6)active bleeding or high risk for bleeding contraindicating treatment with (LMW) heparin or warfarin; 7)chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs); 8)treatment with aspirin in a dosage of more than 100 mg/per day or dual antiplatelet therapy; 9)concurrent treatment with potent P-gp inhibitors; 10)subjects with any condition that, as judged by the investigator, would place the subject at increased risk of harm if he/she participated in the study.
结局指标
主要结局
- Symptomatic recurrent VTE, i.e., the composite of DVT, non-fatal PE, and fatal PE
时间窗: Time Frame: 12 months from time of randomization
次要结局
- - The composite clinical outcome of symptomatic recurrent DVT, non-fatal symptomatic recurrent PE, and all-cause mortality(- Clinically relevant bleeding (i.e., major or clinically relevant non-major bleeding) occurring during treatment)