Comparison of "IN-REC-SUR-E" and LISA in Preterm Neonates With Respiratory Distress Syndrome: a Randomized Controlled Trial (IN-REC-LISA Trial)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 381
- 试验地点
- 2
- 主要终点
- A composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age
研究概览
简要总结
The primary hypothesis of this study is that surfactant administration by INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E), via a high frequency oscillatory ventilation recruitment maneuver increases survival without BPD at 36 weeks' gestational age in spontaneously breathing infants born at 24+0-27+6 weeks' gestation affected by Respiratory Distress Syndrome (RDS) and failing nasal CPAP or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 hours of life compared to less invasive surfactant administration (LISA).
详细描述
BACKGROUND: RDS represents the main cause of respiratory failure in preterm infants and one of the major causes of perinatal morbidity and mortality. Surfactant is a well-established therapy in neonatology, but its optimal administration method remains unresolved, especially with the focus on avoiding MV in preterm infants born before 28 weeks' gestational age (i.e. extremely low gestational age newborns - ELGAN). Duration of MV is a key determinant of the se-verity of bronchopulmo-nary dysplasia (BPD). Although attractive and beneficial in clinical practice, the INtubate, SURfac-tant, Extubate (IN-SUR-E) method cannot be universally applied to all pre-term neonates due to non-homogeneous surfactant distribution and lung derecruitment during intu-bation, resulting in failure rate in preterm infants ranging from 19 % to 69 %. A recent randomized clinical trial showed that the application of a recruitment manoeuvre just before surfactant admin-istration, followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate [IN-REC-SUR-E]), decreased the need for MV during the first 72 h of life compared with IN-SUR-E technique in ELGAN, without in-creasing the risk of adverse neonatal outcomes. Recent-ly, a less invasive surfactant administration (LISA) method was developed with surfactant intro-duced into the trachea of infants breathing spontaneously using a small catheter instead of an endo-tracheal tube. The LISA technique poten-tially combines the benefits of early surfactant treatment CPAP avoiding MV. The last network me-ta-analyses on the comparative efficacy of methods for surfactant administration found that among preterm infants, LISA technique was associated with lower likelihood of mortality, need for MV and BPD compared with IN-SUR-E, but these findings did not include comparison to IN-REC-SUR-E method. More importantly, data for ELGAN are not as robust as for the higher gestation age groups. The same Authors of meta-analysis agree that data for ELGAN are not as ro-bust as for higher gestation age group and that lung recruitment before sur-factant administration (IN-REC-SUR-E) represents a promising novel alternative. The investigators therefore de-signed this study to compare the IN-REC-SUR-E technique with LISA for evaluating the compara-tive effectiveness of these techniques in increasing the survival without BPD of ELGANs.
METHODS: The primary hypothesis of this study is that IN-REC-SUR-E via a HFOV recruitment maneuver increases survival without BPD at 36 weeks' gestational age in spontaneously breathing ELGAN and failing nCPAP or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 hours of life compared to LISA treatment.
Study design: this study is an unblinded multi-center randomized trial of IN-REC-SUR-E vs. LISA in ELGANs.
Randomisation and Masking: infants will be allocated to one of the two treatment groups (1:1) ac-cording to a restricted randomization procedure. Stratification factors will include centre and gesta-tional age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). The table of allocation will not be disclosed to ensure concealment and the randomization will be provided through Research Electron-ic Data Capture (RedCap) web application. The assignment to intervention will be unmasked to all trial par-ticipants: parents, research staff, and medical team will be only aware of study group as-signment af-ter randomization procedures.
Management in the Delivery Room: Neonates will be stabilized after birth with positive pressure us-ing a neonatal mask and a T-piece system (i.e. Neopuff Infant Resuscitator ®, Fisher and Paykel, Auckland, New Zealand). All neonates will be started on nCPAP of at least 6 cm H2O via mask or nasal prongs. Newborns who do not breathe or who are persistently bradycardic within the first 60 seconds after birth will receive positive-pressure ventilation with initial FiO2 of 0.30. Infants that will be transitioned successfully to spontaneous breathing will be transferred to NICU on nCPAP (6-7 cm H2O) or NIPPV. The decision to intubate and start MV in the delivery room will be in ac-cordance with the American Heart Association Guidelines. Method and timing of umbilical cord clamping will be as per standard practice at each site.
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
- Single (Participant)
入排标准
- 年龄范围
- 24 Weeks 至 27 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Infants satisfying the following inclusion criteria will be eligible to participate:
- •Born at 24+0-27+6 in a tertiary neonatal intensive care unit participating in the trial (and)
- •Breathing independently and sufficiently with only nasal CPAP or NIPPV for respiratory support (and)
- •Written parental consent has been obtained (and)
- •Failing nasal CPAP or NIPPV during the first 24 hours of life
排除标准
- •Severe birth asphyxia or a 5-minute Apgar score less than 3
- •Prior endotracheal intubation for resuscitation or insufficient respiratory drive
- •Prolonged (>21 days) premature rupture of membranes
- •Presence of major congenital abnormalities
- •Hydrops fetalis
- •Inherited disorders of metabolism
结局指标
主要结局
A composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age
时间窗: 36 weeks' postmenstrual age or death
A composite outcome of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age is the primary outcome because BPD represents the most severe respiratory morbidity of preterm infants and death is a competing risk. The diagnosis of BPD will be ascertained by a standardized test. Infants remaining on mechanical ventilation or CPAP at 36 weeks postmenstrual age, or those with a supplemental oxygen concentration ≥0.30 to obtain SpO2 between 90% to 94% will receive a BPD diagnosis without additional testing. Infants with a supplemental oxygen concentration \< 0.30 to obtain SpO2 between 90% to 94% or those receiving high-flow nasal cannula therapy will undergo a timed stepwise reduction to room air without any flow. Those in whom the reduction will not be tolerated will receive a BPD diagnosis.
次要结局
- BPD at 36 weeks' s postmenstrual age(36 weeks' s postmenstrual age)
- Duration of invasive respiratory support(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Incidence of a grade 3 or above retinopathy of prematurity (ROP)(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Incidence of any necrotizing enterocolitis (NEC)(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- SpO2/FiO2 at 3 days, 7 days, and thereafter every 7 days until 36 weeks postmenstrual age(36 weeks postmenstrual age)
- Severe intraventricular hemorrhage (grade 3 or 4 based on the Papile criteria)(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Percentage of infants receiving two or more doses of surfactant(First 72 hours of life)
- Death at 36 weeks' s postmenstrual age or before discharge(36 weeks' s postmenstrual age or hospital stay)
- Occurrence of air leaks including pneumothorax or pulmonary interstitial emphysema before discharge(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Rate of patent ductus arteriosus; haemodynamically significant (PDAhs) (i.e.requiring pharmacological treatment with ibuprofen/indomethacin/acetaminophen).(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Duration of non-invasive respiratory support(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Duration of oxygen therapy(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Rate of pulmonary Hemorrhage(First 72 hours of life)
- Incidence of periventricular leukomalacia (PVL)(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Rate of use of systemic postnatal steroids(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Incidence of sepsis defined as a positive blood culture or suggestive clinical and laboratory findings leading to treatment with antibiotics for at least 7 days despite absence of a positive blood culture(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Total in-hospital stay(Participants will be followed for the duration of hospital stay, an expected average of 12 weeks)
- Neurodevelopmental outcomes via Bayley scales of infant development-III and respiratory function testing at 24 months of age.(24 months of age)
研究者
VENTO GIOVANNI
Prof.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS