A Phase 3 Randomized, Double-Blind Active-Controlled (Enoxaparin), Parallel-Group, Multi-Center Study to Evaluate the Safety and Efficacy of Oral Apixaban in Subjects Undergoing Elective Total Knee Replacement Surgery
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3,608
- 试验地点
- 25
- 主要终点
- Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects
研究概览
简要总结
The purpose of this study is to learn if apixaban can prevent blood clots in the leg (deep vein Thrombosis [DVT]) and lung (pulmonary embolism [PE]) that sometimes occur after knee replacement surgery and to learn how apixaban compares to enoxaparin (Lovenox®) for preventing these clots. The safety of apixaban will also be studied.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, 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
- •Men and non-pregnant, non-breastfeeding women
- •18 years or older
- •Scheduled for knee replacement surgery
排除标准
- •hereditary or acquired bleeding disorders
- •clotting disorders
- •bleeding or high risk for bleeding
- •drugs that affect bleeding or coagulation
- •need for ongoing parenteral or oral anticoagulation
研究组 & 干预措施
A1
- placebo
干预措施: Enoxaparin + Placebo (Drug)
A2
- placebo
干预措施: Apixaban + Placebo (Drug)
结局指标
主要结局
Event Rate of the Composite of Adjudicated Venous Thromboembolism (VTE) Events and All-Cause Death With Onset During the Intended Treatment Period - Primary Subjects
时间窗: From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization
An Independent Central Adjudication Committee (ICAC) adjudicated all venograms, suspected symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), acute clinically overt bleeding events, suspected thrombocytopenia, suspected acute MI, suspected acute stroke, and cause of death. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed and reported as percentage (%). Surgery=Day 1; Randomization/Treatment started on Day of Surgery or the next day (Day 1 or Day 2). A mandatory bilateral ascending contrast venogram was performed on all participants after 12 days (±2 days) of study treatment. Intended Treatment Period=starts on the day of randomization; for treated participants, the period ends at the latter of 2 days after last dose of study drug or 14 days after the first dose of study drug; for randomized participants who were not treated, the period ends 14 days after randomization.
Event Rate for Participants With Major Bleeding, Clinically Relevant Non-Major Bleeding, Major or Clinically Relevant Non-Major Bleeding, Any Bleeding With Onset During the Treatment Period - Treated Population
时间窗: First dose of study drug to last dose, plus 2 days post last dose
ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Clinically relevant (CR); Non-Major (N-M) Bleeding. Day 1=Day of surgery. Treatment started (first dose) day of surgery or next day. Treatment continued for 12 days.
Event Rate for Participants With Major Bleeding, Clinically Relevant (CR) Non-Major (N-M) Bleeding , Major or Clinically Relevant (CR) Non-Major (N-M) Bleeding, Any Bleeding With Onset During the Follow-Up Period
时间窗: Last dose of study drug to Day 72 (60 days)
ICAC adjudicated acute clinically overt bleeding events as per International Society on Thrombosis and Hemostasis (ISTH) guidelines modified for surgical patients. Event rate was number of participants with the composite endpoint divided by the number of participants analyzed (%). Follow up Period was from the end of the treatment period (last dose) up to 60 days post last dose, Day 72.
次要结局
- Event Rate of Composite of Adjudicated Proximal DVT, Non-Fatal PE and All-Cause Death With Onset During the Intended Treatment Period PE and All-cause Death During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate of Adjudicated VTE / VTE-related Death With Onset During the Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With Proximal DVT/Non-Fatal PE/ VTE-Related Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Total Participants With Adjudicated VTE/All-Cause Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Total Participants With VTE/ VTE-Related Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With All-Cause Death During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With VTE-Related Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With Symptomatic VTE/ All-Cause Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With Symptomatic VTE/ VTE-Related Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With VTE/Major Bleeding/All-Cause Death With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With PE (Fatal or Non-Fatal), DVT (All, Symptomatic Proximal, and Distal, Asymptomatic) With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With Proximal DVT, Distal DVT, Asymptomatic Proximal DVT, Asymptomatic Distal DVT With Onset During the Intended Treatment Period(From Day 1 or Day 2 to last dose, plus 2 days or 14 days post randomization)
- Event Rate for Participants With Adjudicated Myocardial Infarction (MI) Acute Ischemic Stroke and Thromboembolic Events With Onset During the Treatment Period(From first dose to last dose, plus 2 days (12 days, plus 2))
- Event Rate of Adjudicated MI, Stroke, and Thrombocytopenia Events During the Follow-Up Period(Post last dose of study drug to Day 72 (60 days))
- Number of Participants With Serious Adverse Events (SAEs), Bleeding Adverse Events (AEs), AEs Leading to Discontinuation, and Deaths - Treated Population(First dose to last dose, plus 2 days for AEs (12 + 2 days) or plus 30 days for SAEs (12 + 30 days))
- Mean Change From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period(Baseline to last dose of study drug, plus 2 days)
- Mean Change From Baseline in Heart Rate During the Treatment Period(Baseline to last dose of study drug, plus 2 days)
- Number of Participants With Hematology Laboratory Marked Abnormality During the Treatment Period(First dose to last dose of study drug (12 days), plus 2 days)
- Number of Participants With Other Chemistry Laboratory Marked Abnormalities During the Treatment Period(First dose to last dose of study drug (12 days), plus 2 days)
- Number of Participants With Liver and Kidney Function Chemistry Laboratory Marked Abnormalities During the Treatment Period(First dose to last dose of study drug (12 days), plus 2 days)
- Number of Participants With Electrolyte Chemistry Laboratory Marked Abnormalities During the Treatment Period(First dose to last dose of study drug (12 days), plus 2 days)