Surfactant Therapy Via Supraglottic Airway Device Versus Endotracheal Intubation to Prevent Mechanical Ventilation in Preterm Neonates With Respiratory Distress Syndrome: An Open-label, Non-inferiority, Randomized Controlled Trial at a Level-III Neonatal Intensive Care Unit in Vietnam
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 440
- 试验地点
- 2
- 主要终点
- Failure of surfactant therapy to prevent invasive mechanical ventilation
研究概览
简要总结
Preterm babies often have trouble breathing because their lungs are not fully developed. This condition is called respiratory distress syndrome (RDS). A medicine called surfactant helps their lungs open up and work better. It is usually given through a procedure called INSURE, where a breathing tube is placed into the baby's trachea (via an endotracheal tube) to deliver the medicine. While effective, this method is invasive and can be uncomfortable and risky for the baby.
A newer, less invasive method called SALSA uses a soft mask placed in the throat (a laryngeal mask airway) instead of an endotracheal tube to give the surfactant. This randomized controlled trial will compare SALSA to the traditional INSURE method to see if it works just as well in preventing the need for invasive breathing support within three days of treatment.
The study will include preterm babies born before 34 weeks of pregnancy and weighing at least 750 grams, at Phu San Hanoi Hospital in Vietnam. If SALSA is found to be safe and effective, it may offer a gentler, less invasive, and easier-to-perform option for treating respiratory distress syndrome in premature babies.
详细描述
BACKGROUND
Respiratory distress syndrome (RDS) remains a leading cause of morbidity and mortality among preterm infants worldwide. Surfactant replacement therapy has significantly improved outcomes; however, standard techniques such as INSURE (Intubation-Surfactant-Extubation), while effective in avoiding mechanical ventilation, require endotracheal intubation-a procedure associated with potential complications and demanding considerable clinical expertise. Less invasive methods, such as surfactant administration via a laryngeal mask airway (SALSA), have shown promising results in reducing the need for mechanical ventilation in moderately preterm infants in smaller studies. This approach may be particularly beneficial in low- and middle-income countries (LMICs), where high birth volumes and limited availability of skilled personnel and advanced respiratory support highlight the need for simpler, safer interventions.
Evidence for SALSA in more immature preterm populations and from large randomized controlled trials remains limited. One key barrier to broader adoption has been the lack of appropriately sized supraglottic airway devices for very small infants. A recent feasibility study by this research team, using newly available preterm-sized devices, demonstrated that SALSA is feasible for surfactant delivery in infants weighing between 750 and 1500 grams (NCT06606444). A randomized controlled trial is now warranted to assess the effectiveness and safety of SALSA, particularly in lower-middle-income settings and among extremely low birth weight infants.
AIM AND HYPOTHESIS
This trial primarily aims to evaluate whether surfactant administration via the SALSA method is non-inferior to the current standard INSURE method in preventing IMV in preterm neonates with RDS admitted to a tertiary-level neonatal unit in South-Easia. It also seeks to compare the two methods in terms of safety, ease of use, infant comfort during the procedure, and morbidity during hospital admission.
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
盲法说明
The trial statistician conducting the final analysis will be masked to intervention arm
入排标准
- 年龄范围
- — 至 48 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inborn neonate (=born in the hospital), AND
- •Gestational age <34+0 weeks, AND
- •Birth weight ≥750g, AND
- •Age <48 hours, AND
- •Diagnosis of RDS, confirmed with a chest x-ray or lung ultrasound, except in cases where immediate treatment is necessary and imaging would cause a delay AND
- •Indication for surfactant treatment: Infant on non-invasive support (CPAP/NIPPV) and FiO2 >0.30 to maintain oxygen saturation (SpO2) between 90% and 95%
排除标准
- •Severe respiratory insufficiency in need of intubation at delivery room
- •Severe respiratory insufficiency in need of intubation and invasive mechanical ventilation after arrival to NICU
- •Previous surfactant administration
- •Previous invasive mechanical ventilation
- •Known pneumothorax
- •Major malformations
- •Physician not confident with study intervention
- •The physician decided not to include the patient due to a preference for performing INSURE
- •Excluded due to time constraints preventing completion of informed consent and trial procedures
研究组 & 干预措施
Surfactant therapy administered via supraglottic airway device (SALSA)
Study participants will receive surfactant therapy via a preterm size supraglottic airway device (SALSA).
干预措施: Surfactant Administration Through Laryngeal or Supraglottic Airways (SALSA) (Procedure)
Endotracheal intubation - surfactant administration - and extubation (INSURE)
Study participants will receive surfactant therapy administered via brief endotracheal intubation - surfactant administration - and extubation (INSURE).
干预措施: Intubation - Surfactant administration - Extubation (INSURE) (Procedure)
结局指标
主要结局
Failure of surfactant therapy to prevent invasive mechanical ventilation
时间窗: Within 72 hours after first surfactant administration
Categorical variable (Yes/No). Failure in terms of the need for endotracheal intubation and invasive mechanical ventilation. Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records. Analysis considerations: * If an infant deteriorates after randomization and requires intubation with mechanical ventilation before the allocated intervention can be performed, the case will be classified as failure in the intention-to-treat (ITT) analysis, but excluded from the per-protocol (PP) analysis. * If an infant improves after randomization and the allocated intervention is not required, the case will be included and not considered a failure in the ITT analysis, but excluded from the PP analysis.
Failure of surfactant therapy to prevent invasive mechanical ventilation
时间窗: Within 72 hours after first surfactant administration
Categorical variable (Yes/No). Failure in terms of the need for endotracheal intubation and invasive mechanical ventilation. Decision to initiate mechanical ventilation via intubation will be made at the discretion of the treating physician, guided by the local NICU criteria for mechanical ventilation. Data is extracted from medical records. Analysis considerations: * If an infant deteriorates after randomization and requires intubation with mechanical ventilation before the allocated intervention can be performed, the case will be classified as failure in the intention-to-treat (ITT) analysis, but excluded from the per-protocol (PP) analysis. * If an infant improves after randomization and the allocated intervention is not required, the case will be included and not considered a failure in the ITT analysis, but excluded from the PP analysis.
次要结局
- Time to death(Before discharge (about 6-15 weeks))
- Duration of invasive mechanical ventilation(Before discharge (about 6-15 weeks))
- Duration of Continuous Positive Airway Pressure (CPAP) or Non-invasive Positive Pressure Ventilation (NIPPV)(Before discharge (about 6-15 weeks))
- Duration of any respiratory support (IMV, CPAP, NIPPV or oxygen by nasal cannula)(Before discharge (about 6-15 weeks))
- Duration of hospital admission(Before discharge (about 6-15 weeks))
- Incidence of mortality prior to discharge(Before discharge (about 6-15 weeks))
- Reflux of surfactant during procedure(Directly after first surfactant administration)
- Number of surfactant doses given during admission(Before discharge (about 6-15 weeks))
- Administration of a second surfactant dose within 6 hours of the first dose(6 hours after initial dose)
- Method of subsequent surfactant doses(Before discharge (about 6-15 weeks))
- Time to initiation of invasive mechanical ventilation after the procedure(Before discharge (about 6-15 weeks))
- Invasive mechanical ventilation at any time during admission(Before discharge (about 6-15 weeks))
- Incidence of severe bradycardia(During the procedure, an average of 5-10 minutes)
- Number of placement attempts needed to place LMA or ETT(During the procedure, an average of 5-10 minutes)
- Failure to place supraglottic airway device (SAD) or endotracheal tube (ETT) at first attempt(During the procedure, an average of 5-10 minutes)
- Volume of postintervention surfactant-resembling gastric residuals(Directly after first surfactant administration)
- Proportion (%) of postintervention gastric surfactant aspirated of total surfactant dose(Directly after first surfactant administration)
- Postintervention gastric surfactant aspirated greater than 10% of surfactant dose(Directly after first surfactant administration)
- Incidence of mortality within 7 days after birth(Seven days of age)
- Incidence of bronchopulmonary dysplasia(36 weeks post menstrual age)
- Postnatal steroid treatment before discharge(Before discharge (about 6-15 weeks))
- Incidence of IVH grade III or IV(Before discharge (about 6-15 weeks))
- Incidence of cystic periventricular leukomalacia(Before discharge (about 6-15 weeks))
- Incidence of persistent ductus arteriosus requiring treatment(Before discharge (about 6-15 weeks))
- Incidence of early-onset sepsis(Within 72 hours after birth.)
- Incidence of late-onset sepsis(>72 hours after birth to discharge (about 6-15 weeks))
- Incidence of retinopathy of prematurity, ≥ grade 3(Before discharge (about 6-15 weeks))
- Incidence of transfer due to need of intestinal surgery(Before discharge (about 6-15 weeks))
- Incidence of transfer to higher-level care(Before discharge (about 6-15 weeks))
- Incidence of major morbidity before discharge(Before discharge (about 6-15 weeks))
- Early failure of surfactant therapy(Within 1 hour after first surfactant administration)
- Late failure of surfactant therapy(Between 1 hour and 72 hours after first surfactant administration)
- Time to initiation of invasive mechanical ventilation after the procedure(Before discharge (about 6-15 weeks))
- Invasive mechanical ventilation at any time during admission(Before discharge (about 6-15 weeks))
- Administration of a second surfactant dose within 6 hours of the first dose(6 hours after initial dose)
- Incidence of mortality prior to discharge(Before discharge (about 6-15 weeks))
- Time to death(Before discharge (about 6-15 weeks))
- Duration of invasive mechanical ventilation(Before discharge (about 6-15 weeks))
- Duration of Continuous Positive Airway Pressure (CPAP) or Non-invasive Positive Pressure Ventilation (NIPPV)(Before discharge (about 6-15 weeks))
- Duration of any respiratory support (IMV, CPAP, NIPPV or oxygen by nasal cannula)(Before discharge (about 6-15 weeks))
- Incidence of bronchopulmonary dysplasia(36 weeks post menstrual age)
- Incidence of severe bradycardia(During the procedure, an average of 5-10 minutes)
- Incidence of severe desaturation(During the procedure, an average of 5-10 minutes)
- Number of placement attempts needed to place LMA or ETT(During the procedure, an average of 5-10 minutes)
- Failure to place supraglottic airway device (SAD) or endotracheal tube (ETT) at first attempt(During the procedure, an average of 5-10 minutes)
- Volume of postintervention surfactant-resembling gastric residuals(Directly after first surfactant administration)
- Change in FiO₂ (%) from before the procedure to 3 hours after surfactant administration(Within 10 minutes before the procedure to 3 hours after first surfactant administration)
- Proportion (%) of postintervention gastric surfactant aspirated of total surfactant dose(Directly after first surfactant administration)
- Postintervention gastric surfactant aspirated greater than 10% of surfactant dose(Directly after first surfactant administration)
- Reflux of surfactant during procedure(Directly after first surfactant administration)
- Number of surfactant doses given during admission(Before discharge (about 6-15 weeks))
- Duration of hospital admission(Before discharge (about 6-15 weeks))
- Method of subsequent surfactant doses(Before discharge (about 6-15 weeks))
- Incidence of mortality within 7 days after birth(Seven days of age)
- Postnatal steroid treatment before discharge(Before discharge (about 6-15 weeks))
- Incidence of IVH grade III or IV(Before discharge (about 6-15 weeks))
- Incidence of cystic periventricular leukomalacia(Before discharge (about 6-15 weeks))
- Incidence of pneumothorax, requiring drainage(Before discharge (about 6-15 weeks))
- Incidence of pulmonary haemorrhage, requiring circulatory support(Before discharge (about 6-15 weeks))
- Incidence of persistent ductus arteriosus requiring treatment(Before discharge (about 6-15 weeks))
- Incidence of early-onset sepsis(Within 72 hours after birth.)
- Incidence of retinopathy of prematurity, ≥ grade 3(Before discharge (about 6-15 weeks))
- Incidence of transfer due to need of intestinal surgery(Before discharge (about 6-15 weeks))
- Incidence of late-onset sepsis(>72 hours after birth to discharge (about 6-15 weeks))
- Incidence of major morbidity before discharge(Before discharge (about 6-15 weeks))
- Incidence of transfer to higher-level care(Before discharge (about 6-15 weeks))
研究者
Tobias Alfvén
Professor of Global Child Health
Karolinska Institutet