Multicentre Randomised Controlled Trial of Minimally-invasive Surfactant Therapy in Preterm Infants 25-28 Weeks Gestation on Continuous Positive Airways Pressure
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 486
- 试验地点
- 32
- 主要终点
- Death or physiological bronchopulmonary dysplasia
研究概览
简要总结
Trial question: Does administration of exogenous surfactant using a minimally-invasive technique improve outcome in preterm infants 25-28 weeks gestation treated with continuous positive airway pressure (CPAP)? Trial hypothesis: That early surfactant administration via a minimally-invasive technique to preterm infants on CPAP will result in a lesser duration of mechanical respiratory support, and a higher incidence of survival without bronchopulmonary dysplasia. Trial design: Multicentre, randomised, masked, controlled trial in inborn preterm infants 25-28 weeks gestation, aged less than 6 hours, requiring CPAP because of respiratory distress, with an FiO2 of >=0.3 and CPAP pressure 5-8. Infants randomised to surfactant treatment receive 200 mg/kg of poractant alfa (Curosurf) administered under direct laryngoscopy using a surfactant instillation catheter, followed by reinstitution of CPAP. Controls continue on CPAP. The intervention is masked from the clinical team. Care thereafter is as per usual in both groups, other than the requirement to adhere to intubation criteria. The primary outcome is incidence of death or BPD. Secondary outcomes include incidence of death, major neonatal morbidities (BPD, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotising enterocolitis), pneumothorax and patent ductus arteriosus; need for intubation and surfactant therapy; durations of mechanical respiratory support, intubation, CPAP, intubation and CPAP, high flow nasal cannula (HFNC), oxygen therapy, intensive care stay and hospitalisation; hospitalisation cost; applicability and safety of the MIST procedure; and outcome at 2 years. The sample size is 303/group, allowing detection of a 33% difference in the primary outcome with 90% power. The trial commenced at Royal Hobart Hospital December 2011 and Royal Women's Hospital during 2012, and will ultimately be conducted over 5 years in multiple centres internationally.
详细描述
- OPTIMIST-A TRIAL SUMMARY RESEARCH QUESTION Does administration of exogenous surfactant using a minimally-invasive technique improve outcome in preterm infants 25-28 weeks gestation treated with continuous positive airway pressure (CPAP)?
BACKGROUND Nasal CPAP is often very effective in preterm infants as the initial means of respiratory support, but a sub-group of infants, most with features of respiratory distress syndrome, fail on CPAP and require intubation and ventilation in the first 72 hours. When compared to those in whom CPAP is successful, infants failing CPAP have a substantially longer duration of respiratory support, and a higher risk of adverse outcomes. Decreasing the risk of CPAP failure would thus seem advantageous, and may be achievable with minimally invasive surfactant therapy (MIST), in which surfactant is administered to a spontaneously breathing infant who then remains on CPAP. A technique of MIST (the "Hobart method") using a semi-rigid surfactant instillation catheter has been shown to be feasible in preterm infants on CPAP, and appears to have the potential to alter respiratory course and outcome. This method of MIST now requires evaluation in randomised controlled trials.
RESEARCH DESIGN Multicentre, randomised, masked, controlled trial.
RECRUITMENT Entry criteria Inborn preterm infants 25-28 weeks gestation, aged less than 6 hours, who were not intubated at birth but require CPAP or NIPPV because of respiratory distress, with a CPAP pressure of 5-8 cm H2O and FiO2 ≥0.30.
Exclusion criteria Infants will be excluded if in imminent need of intubation, or if there is a congenital anomaly or alternative cause for respiratory distress.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Minute 至 6 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age 25-28 completed weeks
- •Requiring CPAP or non-invasive positive pressure ventilation with signs of early respiratory distress.
- •CPAP pressure of 5-8 cm H2O and FiO2 >=0.
- •Less than 6 hours of age.
- •Agreement of the Treating Physician in charge of the infant's care.
- •Signed parental consent.
排除标准
- •Previously intubated, or in imminent need of intubation
- •Congenital anomaly or condition that might adversely affect breathing.
- •Identifiable alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia).
- •Lack of availability of an OPTIMIST treatment team.
结局指标
主要结局
Death or physiological bronchopulmonary dysplasia
时间窗: 36 weeks post menstrual age
Composite outcome of death by 36 weeks or physiological bronchopulmonary dysplasia (BPD). Physiological BPD is assessed at 36 weeks post-menstrual age, and is defined as either need for respiratory support (intubation / CPAP / high flow nasal cannula \> 2 L/min) or need for FiO2 \>=0.3 or failure of a room air trial conducted at 36 weeks post-menstrual age. This will be assessed by the research nurse at each centre.
次要结局
- Mortality(36 weeks post menstrual age)
- Major morbidity(36 weeks post menstrual age)
- Pneumothorax(36 weeks post menstrual age)
- Duration of respiratory support(During first hospitalisation (average assessment period 14 weeks))
- Bronchopulmonary dysplasia(36 weeks post menstrual age)
- Duration of bradycardia and hypoxaemia during intervention(During intervention)
- Discomfort during intervention(During intervention)
研究者
Professor Peter Dargaville
Consultant Neonatologist, Paediatric and Neonatal Intensive Care Unit, Royal Hobart Hospital
Menzies Institute for Medical Research