A Phase 3, Open-label, Randomized, Multi-center, Controlled Trial to Evaluate the Pharmacokinetics and Pharmacodynamics of Edoxaban and to Compare the Efficacy and Safety of Edoxaban With Standard of Care Anticoagulant Therapy in Pediatric Subjects From Birth to Less Than 18 Years of Age With Confirmed Venous Thromboembolism (VTE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 290
- 试验地点
- 140
- 主要终点
- Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
研究概览
简要总结
This is an event driven Phase 3, prospective, randomized, open-label, blinded endpoint evaluation (PROBE) parallel group study in subjects with confirmed VTE. This study is designed to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of edoxaban and to compare the efficacy and safety of edoxaban against standard of care in pediatric subjects with confirmed VTE.
详细描述
The objective is to demonstrate the non-inferiority of edoxaban to standard of care (SOC; including low molecular weight heparin (LMWH), vitamin K antagonist (VKA), or synthetic pentasaccharide (SP) Xa inhibitors) in the treatment and secondary prevention of VTE in pediatric subjects with regard to the composite efficacy endpoint (ie, symptomatic recurrent VTE, death as result of VTE, and no change or extension of thrombotic burden) during the first 3-month treatment period.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Day 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female pediatric subjects between birth (defined as 38 weeks gestational age) and less than 18 years of age at the time of consent.
- •Pediatric subjects with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 90 days.
- •Subjects must have received at least 5 days of heparin therapy prior to randomization to treat the newly identified index VTE. In addition, prior to being randomized to edoxaban or SOC, subjects initially treated with VKA are recommended to have an international normalized ratio (INR) < 2.
- •Subject and/or parent(s)/legal guardian(s) or legally acceptable representative is informed and provides signed consent for the child to participate in the study.
- •Female subjects who have menarche must test negative for pregnancy at Screening and must consent to avoid becoming pregnant by using an approved contraception method throughout the study.
排除标准
- •Subjects with active bleeding or high risk of bleeding contraindicating treatment with LMWH, SP Xa inhibitors, VKAs, or direct oral anticoagulants (DOACs; identified high risk of bleeding during prior experimental administration of DOACs).
- •Subjects who have been or are being treated with thrombolytic agents, thrombectomy or insertion of a caval filter for the newly identified index VTE.
- •Administration of antiplatelet therapy is contraindicated in both arms except for low dose aspirin defined as 1-5 mg/Kg/day with maximum of 100 mg/day.
- •Administration of rifampin is prohibited during the study and subjects on concomitant use of rifampin are excluded.
- •Subjects with hepatic disease associated with coagulopathy leading to a clinically relevant bleeding risk (aPTT > 50 seconds or international normalized ratio [INR] > 2.0 not related to anticoagulation therapy) or alanine aminotransferase (ALT) > 5 × the upper limit of normal (ULN) or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total at Screening Visit.
- •Subjects with glomerular filtration rate (GFR) < 30% of normal for age and size as determined by the Schwartz formula.
- •Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed > 99th percentile + 5 mmHg.
- •Subject with thrombocytopenia < 50 × 109/L at Screening Visit. Subjects with a history of heparin-induced thrombocytopenia may be enrolled in the study at the Investigator's discretion.
- •Life expectancy less than the expected study treatment duration (3 months).
- •Subjects who are known to be pregnant or breastfeeding.
- •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, including contraindicated medications.
- •Subjects who participated in another clinical study or treated with an experimental therapy with less than a 30 day washout period prior to identifying the qualifying index VTE.
研究组 & 干预措施
Edoxaban
Edoxaban treatment will be dispensed to the participant on a monthly visit schedule.
Edoxaban will be started orally at the age/weight/renal function appropriate dose, depending on the results of the ongoing U157 study (NCT02303431) for the Treatment Period.
干预措施: Edoxaban (Drug)
Standard of Care
Standard of Care (SOC) treatment will be dispensed to the participant on a monthly visit schedule.
干预措施: Standard of Care (Drug)
结局指标
主要结局
Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
时间窗: Randomization to Month 3
Diagnosis of recurrent venous thromboembolism (VTE) requires the confirmation by diagnostic imaging and at least one of the symptoms of VTE from such areas as lower or upper extremity, catheter related thrombosis, pulmonary embolism, or sinovenous thrombosis.
Number of Participants Who Died as a Result of VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
时间窗: Randomization to Month 3
Death from venous thromboembolism (VTE) is based on objective diagnostic testing, autopsy or death which cannot be attributed to documented cause for which VTE cannot be ruled out.
Number of Participants With No Change or Extension of Thrombotic Burden During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)
时间窗: Randomization to Month 3
No change or extension of thrombotic burden as assessed by quantitative diagnostic imaging of the index qualifying VTE thrombus at baseline and at Month 3. Imaging criteria for VTE included: - Abnormal compression ultrasonography where compression had been normal or, if non-compressible during screening, an increase in diameter of the thrombus during full compression; - An extension of the echogenic intra-luminal thrombus or absence of flow in the central venous system on Doppler ultrasonography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect, or an extension of non-visualization of veins in the presence of a sudden cut-off on venography. - An extension of an intraluminal filling defect, or a new intraluminal filling defect on computed tomography angiogram (CTA).
次要结局
- Number of Participants With Deep Vein Thrombosis, Catheter-related Thrombosis, Sino-venous Thrombosis, and Pulmonary Embolism During the Main, Extension, and Overall Treatment Periods Following Edoxaban or Standard of Care Treatment(From randomization up to Month 12)
- Number of Participants With Major and Clinically Relevant Non-Major Bleeding Events (On Treatment) During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)(Randomization to Month 3)
- Number of Participants With All Bleeding Events (On Treatment) During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)(From randomization up to Month 12)
- Number of Participants With Symptomatic Recurrent Venous Thromboembolism During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)(From randomization up to Month 12)
- Number of Participants With Symptomatic Recurrent VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Individual Component of Primary Efficacy Endpoint)(Randomization to Month 3)
- Number of Participants Who Died as a Result of VTE During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)(From randomization up to Month 12)
- Number of Participants Who Died as a Result of VTE During the Main Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Individual Component of Primary Efficacy Endpoint)(Randomization to Month 3)
- Number of Participants With No Change or Extension of Thrombotic Burden During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)(From randomization up to Month 12)
- Number of Participants With Adjudicated Individual Component of Primary Efficacy Endpoints During the Main Treatment Period Following Edoxaban or Standard of Care Treatment(Randomization to Month 3)
- Number of Participants Reporting Adjudicated All-Cause Mortality During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated)(From randomization up to Month 12)
- Number of Participants With Major and Clinically Relevant Non-Major Bleeding Events (On Treatment) During the Overall Treatment Period Following Edoxaban or Standard of Care Treatment (Adjudicated Composite)(From randomization up to Month 12)