30-day, Single-arm Study of the Safety, Efficacy and the Pharmacokinetic and Pharmacodynamic Properties of Oral Rivaroxaban in Children With Various Manifestations of Venous Thrombosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 64
- 主要终点
- Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events
研究概览
简要总结
The purpose of this study is to find out whether rivaroxaban is safe to use in children and how long it stays in the body. There will also be a check for bleeding and worsening of blood clots.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 6 to < 18 years with documented symptomatic or asymptomatic venous thrombosis treated for at least 2 months or, in case of catheter related thrombosis, treated for at least 6 weeks with LMWH (low molecular weight heparin), , fondaparinux and/or VKA (vitamin K antagonist).
- •Informed consent provided and, if applicable, child assent provided
排除标准
- •Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
- •Symptomatic progression of venous thrombosis during preceding anticoagulant treatment
- •Planned invasive procedures, including lumbar puncture and removal of non peripherally placed central lines during study treatment
- •An estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2
- •Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk or ALT > 5x upper level of normal (ULN) or total bilirubin > 2x ULN with direct bilirubin > 20% of the total
- •Platelet count < 50 x 10^9/L
- •Hypertension defined as > 95th age percentile
- •Life expectancy < 3 months
- •Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e. all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically
- •Concomitant use of strong inducers of CYP3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine
研究组 & 干预措施
Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18
Subjects aged from 12 - <18 years were administered with age and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR (immediate-release) tablet once daily (OD) under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kilogram (kg) received a dose (equivalent to 20 milligram [mg] in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg.
干预措施: Rivaroxaban (Xarelto, BAY59-7939) (Drug)
Comparator, Age: 12 - <18 years
Subjects aged from 12 - <18 years received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or international normalized ratio (INR) adjusted (vitamin K antagonist).
干预措施: Active comparator (Drug)
Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years
Subjects aged from 6 - <12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kg received a dose (equivalent to 20 mg in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg.
干预措施: Rivaroxaban (Xarelto, BAY59-7939) (Drug)
Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years
Subjects aged from 6 - <12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily (BID). Subjects with a body weight of 9 to less than 50 kg received a total daily dose (equivalent to 20 mg in adults) ranging from 6.4 to 15 mg and subjects with a body weight of greater than or equal to 50 kg received a total daily dose of 20 mg.
干预措施: Rivaroxaban (BAY59-7939) suspension (Drug)
Comparator, Age: 6 - <12 years
Subjects aged from 6 - <12 years received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or INR-adjusted (vitamin K antagonist).
干预措施: Active comparator (Drug)
结局指标
主要结局
Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events
时间窗: From start of study drug administration until end of the 30-day treatment period
Central independent adjudication committee (CIAC) classified bleeding as follows: Major bleeding is defined as overt bleeding and: * associated with a fall in hemoglobin of 2 gram/decilitre (g/dL) or more, or * leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or * occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or * contributing to death. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding, but associated with: * medical intervention, or * unscheduled contact (visit or telephone call) with a physician, or * cessation (temporary) of study treatment, or * discomfort for the child such as pain or * impairment of activities of daily life (such as loss of school days or hospitalization).
次要结局
- Number of Subjects With Symptomatic Recurrent Venous Thromboembolism(From start of study drug administration until end of the 30-day treatment period)
- Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Specified Time Points(0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31)
- Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden(Repeat imaging at the end of the 30 day treatment period)
- Change From Baseline in Prothrombin Time at Specified Time Points(0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31)
- Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points(0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31)
- Anti-factor Xa Values at Specified Time Points(0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31)