An Open-Label, Multicenter, Randomized, Controlled Study in Spontaneously Breathing Preterm Neonates With Respiratory Distress Syndrome to Compare Two Procedures for Porcine Surfactant (Poractant Alfa, CUROSURF®) Administration: A Less Invasive Method (LISA) During Non-invasive Ventilation (NIV) and the Conventional Administration During Brief Invasive Ventilation.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 33
- 试验地点
- 26
- 主要终点
- Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion
研究概览
简要总结
This study compared the administration of porcine surfactant (poractant alfa, Curosurf®) through a less invasive method (LISA), using a thin catheter, CHF 6440 (LISACATH®), during non-invasive ventilation (CPAP, NIPPV, BiPAP) with an approved conventional surfactant administration during invasive ventilation followed by rapid extubation in terms of short term and mid-term safety and efficacy in spontaneously breathing preterm neonates who have clinical signs of respiratory distress syndrome (RDS).
详细描述
This study was an open-label, multicentre, randomized, controlled study of spontaneously breathing neonates with RDS. Neonates were evaluated according to the selection criteria and then randomized to surfactant treatment via LISA or standard administration procedure. The enrolment was staggered: the gestational age was restricted to 27+0 weeks up to 28+6 weeks for the first 15 neonates. Provided no safety concerns were raised, the enrolment was planned to be extended to the whole population (i.e. 25+0 weeks up to 28+6 weeks). Enrolled neonates were evaluated in a main phase of the trial until discharge or 40 weeks post-menstrual age (PMA), whichever came first. Their clinical status and neurodevelopment was to be assessed at 24-month corrected age as a separate stand-alone visit.
The Sponsor decided to terminate the study early, due to uncertain sufficient availability of the CHF 6440 catheter.
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
- None
入排标准
- 年龄范围
- 30 Minutes 至 24 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth
- •Preterm neonates of either sex aged ≥30 minutes and <24 hours, spontaneously breathing and stabilized on non-invasive ventilation (NIV).
- •Gestational age of 25+0 weeks up to 28+6 completed weeks, except for the first 15 enrolled neonates in which the gestational age will be restricted to 27+0 weeks up to 28+6 weeks.
- •Clinical course consistent with RDS.
- •Fraction of inspired oxygen (FiO2) ≥0.30 to maintain preductal oxygen saturation (SpO2) between 88-95%.
排除标准
- •Need for immediate endotracheal intubation for cardiopulmonary resuscitation or insufficient respiratory drive
- •Use of nasal high frequency oscillatory ventilation (nHFOV) prior to study entry
- •Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide)
- •Known genetic or chromosomal disorders, major congenital anomalies (congenital heart diseases, myelomeningocele etc)
- •Mothers with prolonged rupture of the membranes (> 21 days duration)
- •Presence of air leaks if identified and known prior to study entry
- •Evidence of severe birth asphyxia (e.g. continued need for resuscitation at 10 minutes after birth, altered neurological state, or neonatal encephalopathy)
- •Neonatal seizures prior to study entry
- •Any condition that, in the opinion of the Investigator, would place the neonate at undue risk
- •Participation in another clinical trial of any medicinal product, placebo, experimental medical device, or biological substance conducted under the provisions of a protocol on the same therapeutic target.
研究组 & 干预措施
Curosurf LISA
Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS.
A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed.
After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed.
干预措施: LISA combination product (Curosurf+catheter CHF6440) (Combination Product)
Curosurf Endotracheal Tube
Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS.
A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed.
After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed.
干预措施: Curosurf through conventional administration (endotracheal tube) (Drug)
结局指标
主要结局
Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion
时间窗: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Number of attempts required to achieve first successful insertion is presented by treatment group.
Safety: Study Treatment Administration: Duration of Surfactant Administration
时间窗: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Duration of surfactant administration is presented by treatment group.
Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment
时间窗: First 72 hours of life.
Extent of exposure to study treatment is summarized by treatment group. Number of participants who received 1, 2, or 3 doses of treatment. All neonates received the first administration of Curosurf® 200 mg/kg. In case of lack of efficacy or clinical deterioration, a second dose of Curosurf® 100 mg/kg was administered using the same technique as the first dose. Neonates could receive a third Curosurf® 100 mg/kg dose if needed, administered using a standard technique. Results are presented as the number of neonates who received 1, 2, or 3 doses of Curosurf®, administered.
Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube
时间窗: At first surfactant administration, up to Day 1.
Number of participants for whom the first attempt failed to insert the catheter/endotracheal tube and the percentage of neonates with first failed attempt, is presented by treatment group.
Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization
时间窗: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Number of manoeuvres (attempts) discontinued, due to neonate's severe destabilization is presented by treatment group.
Safety: Study Treatment Administration: Duration of the Whole Procedure
时间窗: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Duration of the whole procedure (starting from the insertion of laryngoscope up to the removal of the catheter/ETT), is presented by treatment group.
Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion)
时间窗: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Number of device misallocation for LISA administration group (esophageal insertion). Data was not collected from participants in the "Curosurf Endotracheal Tube" -- the control arm of the study, because it is not applicable.
次要结局
- Efficacy: Blood Gas Analysis Parameters -- pH(First 72 hours of life (1h, 6h, 24h, 48h, 72h))
- Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV)(First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks Post-Menstrual Age (PMA).)
- Efficacy: Neonates Needing Additional Surfactant Doses(First 72 hours of life.)
- Efficacy: Preductal Oxygen Saturation (SpO2)(Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.)
- Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study(Up to 28 days PNA, Up to 36 weeks PMA)
- Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study(First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks PMA)
- Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2)(First 72 hours of life (1h, 6h, 24h, 48h, 72h))
- Efficacy: Blood Analysis Parameter -- Lactate(First 72 hours of life (1h, 6h, 24h, 48h, 72h))
- Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant(First 72 hours of life.)
- Efficacy: Fraction of Inspired Oxygen (FiO2)(Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.)
- Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period(First 72 hours of life, up to 28 days post-natal age (PNA), Up to 36 weeks Post-menstrual age (PMA))
- Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-)(First 72 hours of life (1h, 6h, 24h, 48h, 72h))
- Efficacy: Blood Analysis Parameter -- Base Excess(First 72 hours of life (1h, 6h, 24h, 48h, 72h))
- Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio(Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.)
- Efficacy: Duration of Invasive Mechanical Ventilation During the Study(First 72 hours of life)
- Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2)(First 72 hours of life (1h, 6h, 24h, 48h, 72h))