LISA vs INSURE in the Treatment of Respiratory Distress Syndrome in Preterm Infants

Study Overview
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Brief Summary
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To evaluate the efficacy of less invasive surfactant administration（LISA ）technique in the treatment of neonatal respiratory distress syndrome（NRDS） by comparing with the traditional Intubate-Surfactant-Extubate（INSURE） technique.

Detailed Description
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Background: Neonatal Respiratory distress syndrome (NRDS) is the most common cause of respiratory problems in premature babies. Surfactant administration involved with endotracheal intubation and mechanical ventilation has proven to be a effective treatment, however, it is associated with a risk of barotrauma, volutrauma and bronchopulmonary dysplasia(BPD). In recent years, some studies have demonstrated that prophylactic INSURE did not lead to a higher survival without BPD, and LISA technique is recommended. However there is no multicenter and Large sample research about it. The aim of this multicenter trial is to compare the efficacy between LISA-treated and INSURE-treated premature Preterm babies with respiratory distress syndrome(RDS). Methods/Design：In this multicenter, randomized, cohort, prospective trial, 200 preterm infants from 18 neonatal intensive care units in AnHui province whose gestational age (GA) less than 32 weeks with a diagnosis of RDS will be randomized to LISA-treated group and INSURE-treated group. The primary outcomes include rate of intubation,incidence of bronchopulmonary dysplasia(BPD).The secondary outcomes include arterial blood gas analysis,severity of RDS,the incidence of Patent ductus arteriosus(PDA),Pneumothorax,Abdominal Distention,Neonatal Necrotizing Enterocolitis(NEC,>Stage II), Retinopathy of Prematurity( ROP,≥ Stage II), Intraventricular Hemorrhage (IVH, ≥ Grade Ⅲ), Periventricular Leukomalacia(PVL) , mortality, days on noninvasive respiratory support,days on supplemental oxygen and days of hospitalization.Other secondary outcomes include scores of Gesell development Scales of infant development at 3 years of corrected age.

Official Title
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The Efficacy of LISA Technology With Noninvasive Ventilation in the Treatment of Respiratory Distress Syndrome in Preterm Neonates

Conditions
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Preterm Infants

Intervention / Treatment
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* Procedure: Intubate-Surfactant-Extubate(INSURE)
* Procedure: less invasive surfactant administration(LISA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age (GA) less than 32 weeks diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (Progressive dyspnea, nasal flaring and or grunting), chest X-ray findings and need for noninvasive ventilation support(fraction of inspired oxygen>40％) in 6 hours after birth informed parental consent has been obtained Exclusion Criteria: severe RDS have been treated with endotracheal intubation,surfactant and mechanical ventilation major congenital malformations or complex congenital heart disease Pulmonary hemorrhage Cardiopulmonary failure septicemia, Intraventricular Hemorrhage (IVH, ≥ Grade Ⅲ), and Congenital genetic metabolic disease transferred out of the NICUs(neonatal intensive care units) with surgical treatment or other intervention

Ages Eligible for Study
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Minimum Age: 25 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: INSURE<br>Intubate-Surfactant-Extubate(INSURE) technique is a Important treatment in premature infants with RDS. | Procedure: Intubate-Surfactant-Extubate(INSURE)<br>* Infants are given an endotracheal intubation, with manual lung inflation in order to keep the oxygen supply，and the surfactant(kelisu,China Resources Shuanghe Pharmaceutical) was slowly instilled into the airway through the tracheal tube, and the tracheal tube was removed for non-invasive NCPAP(nasal continuous positive airway pressure)-assisted breathing.<br>|
| Experimental: LISA<br>Less invasive surfactant administration(LISA) technique is a Important treatment in premature infants with RDS. | Procedure: less invasive surfactant administration(LISA)<br>* Infants are spontaneously breathing with nasal CPAP(continuous positive airway pressure) support without manual lung inflation and surfactant(kelisu,China Resources Shuanghe Pharmaceutical) is administered through vocal cords via a smaller catheter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of intubation | The criteria for endotracheal mechanical ventilation were as follows: severe apnea and bradycardia (defined as recurrent apnea with > 3 episodes per hour associated with heart rate < 100/min, a single episode of apnea that required bag and mask ventilation), hypoxia (FiO2>0.6 with PaO2<50mmHg or TcSO<0.85), severe respiratory acidosis (PaCO2 > 60 mmHg with pH<7.20). | during the first 3 days after birth | 
| The incidence of bronchopulmonary dysplasia | BPD was diagnosed and classified based on the Practical neonatology 4th edition:Need for O2 supplementation(FiO2>0.21) for at least 28 days after birth. | at a post-menstrual age of 36 weeks or at discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on of arterial blood gas analysis | The improvement of PaO2 and PaCO2 in two groups children with LISA technique | during the whole procedure of surfactant replacement,up to 3 days after birth | 
| The Incidence of Patent ductus arteriosus | PDA was diagnosed based on echocardiography | during hospitalization, up to 60 days | 
| The Incidence of Pneumothorax | Pneumothorax was diagnosed based on clinical manifestations and features of chest x-ray | during non-invasive ventilation, up to 30 days | 
| The Incidence of Abdominal Distention | Abdominal circumference was measured 3 times a day during non-invasive ventilation | during non-invasive ventilation, up to 30 days | 
| The Incidence of Neonatal Necrotizing Enterocolitis(>Stage II) | Neonatal Necrotizing Enterocolitis was diagnosed by clinical manifestations and features of abdominal x-Ray based on the Practical neonatology 4th edition | during hospitalization, up to 60 days | 
| The Incidence of Retinopathy of Prematurity( ≥ Stage II) | The criteria for Retinopathy of prematurity (>Stage II); extraretinal fibrovascular proliferation neovascularization extends from ridge into the vitreous. | at a post-menstrual age of 36 weeks or at discharge | 
| The Incidence of Intraventricular Hemorrhage (IVH, ≥ Grade Ⅲ) | The criteria for intraventricular hemorrhage (IVH, ≥ grade Ⅲ): intraventricular hemorrhage with ventricular dilatation and intraventricular hemorrhage with paren-ehymal hemorrhage. | during hospitalization, up to 60 days | 
| The Incidence of Periventricular Leukomalacia | Periventricular Leukomalacia was diagnosed based on cranial MRI | during hospitalization, up to 36 months | 
| Predischarge Mortality |  | during hospitalization, up to 60 days | 
| The Time of Non-invasive Ventilation | Hours | during hospitalization, up to 60 days | 
| Days on supplemental oxygen | Days | during hospitalization, up to 60 days | 
| Length of Hospitalization | Days | during hospitalization, up to 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NRDS, preterm infants, LISA, INSURE