Positive End-Expiratory Pressure (PEEP) Levels During Resuscitation of Preterm Infants at Birth (The POLAR Trial).
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 906
- 试验地点
- 53
- 主要终点
- The prevalence of the composite outcome of either death or bronchopulmonary dysplasia (BPD), as assessed by standard oxygen reduction test.
研究概览
简要总结
Premature babies often need help immediately after birth to open their lungs to air, start breathing and keep their hearts beating. Opening their lungs can be difficult, and once open the under-developed lungs of premature babies will often collapse again between each breath. To prevent this nearly all premature babies receive some form of mechanical respiratory support to aid breathing. Common to all types of respiratory support is the delivery of a treatment called positive end-expiratory pressure, or PEEP. PEEP gives air, or a mixture of air and oxygen, to the lung between each breath to keep the lungs open and stop them collapsing.
Currently, clinicians do not have enough evidence on the right amount, or level, of PEEP to give at birth. As a result, doctors around the world give different amounts (or levels) of PEEP to premature babies at birth.
In this study, the Investigators will look at 2 different approaches to PEEP to help premature babies during their first breaths at birth. At the moment, the Investigators do not know if one is better than the other. One is to give the same PEEP level to the lungs. The others is to give a high PEEP level at birth when the lungs are hardest to open and then decrease the PEEP later once the lungs are opened and the baby is breathing.
Very premature babies have a risk of long-term lung disease (chronic lung disease). The more breathing support a premature baby needs, the more likely the risk of developing chronic lung disease. The Investigators want to find out whether one method of opening the baby's lungs at birth results in them needing less breathing support.
This research has been initiated by a group of doctors from Australia, the Netherlands and the USA, all who look after premature babies.
详细描述
All infants born <29 weeks' postmenstrual age (PMA) require positive end-expiratory pressure (PEEP) at birth. PEEP is a simple, feasible and cost-effective therapy to support extremely preterm infants that is used globally. The effective and safe level of PEEP to use after preterm birth remains the most important unanswered question in neonatal respiratory medicine.
The Investigators will undertake an international multi-centre randomised controlled trial to address in extremely preterm infants, whether the use of a high, dynamic PEEP level strategy to support the lung during stabilisation ('resuscitation') at birth, compared to the current practice of a static PEEP level, will reduce the rate of death or bronchopulmonary dysplasia (BPD).
This trial will address the following four key knowledge gaps:
- Assessing whether individualising (dynamic) PEEP is superior to static PEEP
- The uncertainty regarding applied pressure strategies to support the lung during stabilisation at birth arising from the lack of a properly powered, well-designed randomised trial specifically addressing important outcomes for respiratory support in the Delivery Room
- The optimal PEEP strategy to use
- Determining the differential effects of PEEP at different gestational ages.
For this study, the term PEEP refers to the delivery of positive pressure (via a bias flow of gas) to the lungs during expiration by any method of assisted respiratory support, this includes:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
The clinical team within the Delivery Room managing enrolled and randomised infants will not be masked/blinded to the intervention.
Members of the Research Team at participating sites will also not be masked/blinded to the intervention.
Research staff based at the central Trial Coordinating Centre (TCC), the Data Coordinating Centre (DCCe) and the Trial Statistician will be blinded to assigned treatment.
入排标准
- 年龄范围
- 23 Weeks 至 28 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants born between 23 weeks 0 days and 28 weeks 6 days PMA (by best obstetric estimate).
- •Receives respiratory intervention (resuscitation) at birth with CPAP and/or positive pressure ventilation in the Delivery Room, to support transition and/or respiratory failure related to prematurity.
- •Has a parent or other legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf either prospectively or after birth and randomisation if prenatal consent was not possible (at sites where the Ethics Committee permits waiver of prospective consent).
排除标准
- •Not for active care based on assessment of the attending clinician or family decision
- •Anticipated severe pulmonary hypoplasia due to rupture of membranes <22 weeks with anhydramnios or fetal hydrops
- •Major congenital anomaly or anticipated alternative cause for respiratory failure
- •Refusal of informed consent by their legally acceptable representative
- •Does not have a guardian who can provide informed consent.
研究组 & 干预措施
Static PEEP Group
Delivery of PEEP at 5-6 cmH2O via a T-piece resuscitator using an initial fraction of inspired oxygen (FiO2) of 0.30 via local standard interface (facemask, nasopharyngeal tube or nasal prong). FiO2 and other aspects of respiratory care are then titrated using a standardised resuscitation algorithm.
干预措施: Positive End-Expiratory Pressure (PEEP) (Procedure)
Dynamic PEEP Group
Dynamic delivery of PEEP at 8 cmH2O via a T-piece resuscitator using an initial fraction of inspired oxygen (FiO2) of 0.30 via local standard interface (facemask, nasopharyngeal tube or nasal prong). PEEP levels increased step-wise to 10 and/or 12 cmH2O if FiO2/respiratory care needs to be escalated as per a standardised resuscitation algorithm.
If an infant shows evidence of respiratory improvement during resuscitative care, PEEP will be reduced in a stepwise method by 2 cmH2O each reduction, but to no lower than 8 cmH2O.
干预措施: Positive End-Expiratory Pressure (PEEP) (Procedure)
结局指标
主要结局
The prevalence of the composite outcome of either death or bronchopulmonary dysplasia (BPD), as assessed by standard oxygen reduction test.
时间窗: At 36 weeks post menstrual age.
This is defined as the proportion of participants in the analysis set with a confirmed death date or a diagnosis of bronchopulmonary dysplasia (BPD), at 36 weeks post menstrual age.
次要结局
- The rate/incidence of grade 3 and 4 intraventricular haemorrhage within the first 72 hours of life, as defined via imaging.(From the time of birth until 72 hours post birth.)
- Length of stay in hospital(Up to 44 weeks PMA)
- The rate/incidence of failure of non-invasive ventilation in first 72 hours, as assessed by intubation status.(From the time of birth until 72 hours post birth.)
- The rate/incidence of surfactant therapy requirement within the first 72 hours of life, as assessed by surfactant therapy status.(From the time of birth until 72 hours post birth.)
- Significant brain injury (IVH grade 3 or 4, periventricular leukomalacia)(36-week corrected PMA.)
- Highest PEEP used during non-invasive ventilation(Birth to 10 days of age.)
- Postnatal steroid use(36 week PMA.)
- The grade of bronchopulmonary dysplasia (BPD), based on the results of an oxygen reduction test.(At 36 weeks post menstrual age.)
- Incidence of air leak and/or pulmonary interstitial emphysema (defined on chest radiograph; CXR) in the first 10 days after birth(Birth to 10 days of age.)
- Airleak(During hospital stay, on average until 36 weeks PMA.)
- Retinopathy of prematurity (stage 3 or higher or requiring treatment)(36-week corrected PMA.)
- Oxygen requirement at discharge to home(Up to 44 weeks PMA)
- Patent ductus arteriosus requiring medical or surgical therapy in first 72 hours(72 hours of age.)
- Oxygen requirement ≥50% for 3 or more consecutive hours in first 72 hours(From the time of birth until 72 hours post birth.)
- Supplementary oxygen use(From the time of birth until 10 days of age.)
- Incidence of Death at 36 week PMA(At 36 weeks post menstrual age.)
- Incidence of Bronchopulmonary dysplasia (BPD) at 36 week PMA(At 36 weeks post menstrual age.)
- Meeting the protocol criteria for failure of non-invasive ventilation during the intervention period(Up to the first 20 minutes after commencing respiratory support following birth.)
- Inotrope use(36 week PMA.)
- The rate/incidence of death within the first 10 days of life, as assessed by date of death.(From the time of birth until 10 days post birth.)
- The rate/incidence of treatment failure within the delivery room, as assessed by intubation status.(From the time of birth through transfer to NICU (within two hours from birth))
- Invasive ventilation at day 10 of age(First 10 days after birth.)
- Duration of respiratory support(36 week PMA.)