A Phase 3 Randomized, Double-Blind, Parallel-group, Multi-center Study of the Safety and Efficacy of Apixaban for Prophylaxis of Venous Thromboembolism in Acutely Ill Medical Subjects During and Following Hospitalization.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6,758
- 试验地点
- 48
- 主要终点
- Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population
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 within patients hospitalized for acute medical illness, 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
- 40 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
- •40 years or older
- •hospitalized with congestive heart failure or acute respiratory failure
- •infection (without septic shock)
- •acute rheumatic disorder
- •inflammatory bowel disease
排除标准
- •patients with venous thromboembolism (VTE)
- •active bleeding or at high risk of bleeding
- •unable to take oral medication
- •with diseases requiring ongoing treatment with anticoagulants or antiplatelets other than aspirin at a dose ≤ 165 mg/day.
研究组 & 干预措施
Arm 1
While hospitalized, Apixaban plus Placebo
Apixaban (Tablets, Oral, 2.5 mg), Placebo (Syringes, SC)
After hospital discharge, Apixaban
Apixaban (Tablets, Oral, 2.5 mg)
干预措施: Apixaban (Drug)
Arm 2
While hospitalized, Enoxaparin plus Placebo
Enoxaparin (Syringes, SC, 40 mg), Placebo (Tablets, Oral)
After hospital discharge: Placebo
Placebo (Tablets, Oral)
干预措施: Enoxaparin (Drug)
结局指标
主要结局
Incidence of Composite of Adjudicated Total Venous Thromboembolism (VTE) and VTE-related Death During the Intended Treatment Period - Primary Efficacy Population
时间窗: Intended Treatment Period
VTE: nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death: fatal PE or sudden death for which VTE could not be excluded as a cause. Intended Treatment Period=period that started on day of randomization: period ended (for treated) at latter of a) 2 days after last dose of study drug and b) 32 days after first dose of study drug; period ended (for not treated) 32 days after randomization. A bilateral compression ultrasound (CUS) was performed between Days 5 and 14 for detection of asymptomatic proximal DVT unless a symptomatic VTE was confirmed prior. CUS was also performed on Day 30 ± 2 except for those participants who had a confirmed symptomatic VTE or proximal asymptomatic DVT prior to that time. All efficacy events were adjudicated by the Independent Central Adjudication Committee (ICAC). Event rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Incidence of Major Bleeding During the Treatment Period in Treated Participants
时间窗: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Major bleeding was adjudicated by an ICAC using criteria from the International Society on Thrombosis and Hemostasis (ISTH) and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or bleeding in a critical site or bleeding which is fatal. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Incidence of Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants
时间窗: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Bleeding was adjudicated by an ICAC using criteria from the ISTH. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis, if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Incidence of Composite of Major or Clinically Relevant Non-Major (CRNM) Bleeding During the Treatment Period in Treated Participants
时间窗: Day 1, first dose of study drug, to last dose of study drug plus 2 days
Bleeding was adjudicated by an ICAC using criteria from the ISTH. Major bleeding: acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or bleeding in a critical site or bleeding which is fatal. CRNM bleeding: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding; spontaneous hematuria; macroscopic gastrointestinal hemorrhage; rectal blood loss. Treatment Period=onset from first dose of study drug through 2 days after last dose of study drugs. Incidence: Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
Incidence of All Bleeding During the Treatment Period in Treated Participants
时间窗: Day 1, first dose of drug to last dose of drug plus 2 days
Bleeding was adjudicated by an ICAC using criteria from the ISTH. Treatment Period=includes measurements or events with onset from first dose of study drug through 2 days after the last dose of study drugs, for bleeding endpoints. Incidence determined by Event Rate (%): n/N\*100 (n=number with observation; N=total efficacy evaluable participants).
次要结局
- Incidence of Adjudicated VTE-Related Death With Onset During the Intended Treatment Period in Randomized Participants(Intended Treatment Period)
- Incidence of Adjudicated Symptomatic VTE or All-Cause Death With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Key Secondary Efficacy Evaluable Participants(Day 1 to last dose of parenteral study drug plus 1 day)
- Incidence of Adjudicated Total VTE and VTE-Related Death During Parenteral Treatment in Secondary Efficacy Evaluable Participants(Day 1 to last dose of parenteral study drug plus 1 day)
- Incidence of Adjudicated Total VTE or All-Cause Death With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Proximal DVT, Non-Fatal PE or All-Cause Death With Onset During the Intended Treatment Period(Intended Treatment Period)
- Mean Change From Baseline in Systolic Blood Pressure in Treated Participants During Treatment Period(Day 1 to last dose of study drug plus 2 days)
- Mean Change From Baseline in Heart Rate in Treated Participants(Day 1 to last dose of study drug plus 2 days)
- Number of Participants With Marked Abnormalities in Hematology Laboratory Tests During Treatment Period in Treated Participants(Day 1 to last dose of study drug plus 2 days)
- Number of Participants With Marked Abnormalities in Electrolyte Laboratory Tests During Treatment Period in Treated Participants(Day 1 to last dose of study drug plus 2 days)
- Number of Participants With Marked Abnormalities in Kidney and Liver Function Laboratory Tests During the Treatment Period in Treated Participants(Day 1 to last dose of study drug plus 2 days)
- Incidence of Adjudicated Proximal DVT, Non-Fatal PE or VTE-Related Death, With Onset During the Intended Treatment Period(Intended Treatment Period)
- Symptomatic Adjudicated VTE or VTE-Related Death With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of All VTE or Major Bleeding or All-Cause Death During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated PE With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Non-Fatal PE With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Symptomatic DVT With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Proximal DVT With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Symptomatic Distal DVT With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Symptomatic Proximal DVT With Onset During the Intended Treatment Period(Intended Treatment Period)
- Incidence of Adjudicated Asymptomatic Proximal DVT With Onset During the Intended Treatment Period(Intended Treatment Period)
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Bleeding AEs, Deaths, and Discontinuations Due to AEs During the Treatment Period in Treated Participants(Day 1, first dose of study drug, to last dose of study drug plus 2 days (AEs), plus 30 days (SAEs, Deaths))
- Mean Change From Baseline in Diastolic Blood Pressure in Treated Participants During Treatment Period(Day 1 to last dose of study drug plus 2 days)
- Number of Participants With Marked Abnormalities in Glucose, Creatine Kinase, Uric Acid, and Total Protein Laboratory Tests During the Treatment Period in Treated Participants(Day 1 to last dose of study drug plus 2 days)
- Incidence of Events of Special Interest of Adjudicated Myocardial Infarction, Stroke, and Thrombocytopenia During the Treatment Period in Treated Participants(Day 1 to last dose of study drug plus 2 days)
- Number of Participants With Events of Special Interest for Liver Function and Neurology During Treatment Period in Treated Participants With Available Measurements(Day 1 to last dose of study drug plus 2 days (AEs) and plus 30 days (SAEs))
- Number of Participants With Liver-Related Elevations During the Treatment Period in Treated Participants(Day 1 to last dose of study drug plus 2 days)