Intravenous Remodulin (Treprostinil) as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn: A Randomized, Placebo-Controlled, Safety and Efficacy Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 42
- 试验地点
- 14
- 主要终点
- Number of Subjects Experiencing Clinical Worsening
研究概览
简要总结
This study assessed the safety and treatment effect of intravenous (IV) Remodulin as an add-on therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN).
详细描述
This study was designed to investigate if the addition of Remodulin reduced the rate of clinical worsening (defined as the need for additional treatment targeting PPHN, need for extracorporeal mechanical oxygenation [ECMO], or death) in neonatal subjects with PPHN who did not show an adequate response to inhaled nitric oxide (iNO). This study was part of a pediatric investigation plan agreed upon by the EMA (EMEA 000207-PIP01-08-M08).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Hour 至 14 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parent(s) or legal guardian provided consent for the subject to participate
- •Weight at least 2 kg at Screening
- •Gestational age of ≥34 weeks and ≤14 days old at Screening
- •Diagnosis of PPHN, which was either idiopathic in nature or associated with the following: meconium aspiration syndrome, pneumonia, respiratory distress syndrome, sepsis, birth hypoxia, perinatal encephalopathy, or unilateral congenital diaphragmatic hernia
- •Currently requiring ventilator support
- •Two consecutive oxygenation index (OI) of 15 or greater separated by at least 30 minutes, after receiving iNO for at least 3 hours
- •Echocardiographic (ECHO) evidence of pulmonary hypertension with elevated right ventricle pressure
- •Dedicated venous access for the administration of study drug (central line or peripherally inserted central venous catheter)
排除标准
- •Previous or concurrent use of a phosphodiesterase-5 inhibitor, endothelin receptor antagonist, or prostanoid
- •Significant congenital heart disease as detected by ECHO, minor valvular abnormalities, or expected transitional findings such as a patent foramen ovale, or patent ductus arteriosus.
- •Clinically significant, untreated active pneumothorax at Screening
- •Evidence of clinically significant bleeding at Screening
- •Necrotizing enterocolitis (≥Bells stage II at Screening)
- •Uncontrolled hypotension (mean systemic pressures ≤35 mmHg at Screening)
- •Uncontrolled coagulopathy and / or untreated thrombocytopenia (<50,000 platelets/µL at Screening)
- •History of severe (Grade 3 or 4) intracranial hemorrhage at Screening
- •Currently receiving extracorporeal mechanical oxygenation (ECMO) or had immediate plans to initiate ECMO
- •Expected duration on mechanical ventilation of <48 hours
- •Life expectancy was less than 2 months or had a lethal chromosomal anomaly
- •Contraindication to ECMO
- •Bilateral congenital diaphragmatic hernia
- •Active seizures at Screening
- •Currently participating in another clinical drug study
研究组 & 干预措施
IV Remodulin
The starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose.
干预措施: IV Remodulin (Drug)
Placebo
The starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Subjects Experiencing Clinical Worsening
时间窗: From Baseline to Day 14
Clinical worsening was a composite endpoint defined by the occurrence of 1 of the following: death, initiation of ECMO per institutional policies, or need for additional treatment (initiation of additional targeted pulmonary vasodilator therapy).
次要结局
- Change in Pre- and Post-ductal Oxygen Saturation (SpO2)(From Baseline to Hours 6, 12, 24, and 72)
- Change in Oxygenation Index (OI)(From Baseline to Hours 12, 24, and 72; Days 7 and 14; and/or prior to study drug discontinuation/weaning)
- Time to Initiation of ECMO(From Baseline to Day 56)
- Change in P/F Ratio(From Baseline to Hours 12, 24, and 72)
- Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)(From Baseline to Days 1, 2, 3, 7, and 14 (or prior to hospital discharge))
- Time to Clinical Worsening(From Baseline to Day 56)
- Time to Discontinuation of Inhaled Nitric Oxide (iNO)(From Baseline to Day 56)