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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Preterm Infants
• Intervention / Treatment: Procedure: Intubate-Surfactant-Extubate(INSURE); Procedure: less invasive surfactant administration(LISA)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhang Lan, PhD; Phone Number: 18256935186; Email: moaana@163.com
• Study Contact Backup: Name: Pan Jiahua, PhD; Phone Number: 13866167758; Email: panjiahua1960@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: INSURE; Intubate-Surfactant-Extubate(INSURE) technique is a Important treatment in premature infants with RDS.	Procedure: Intubate-Surfactant-Extubate(INSURE); 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.
Experimental: LISA; Less invasive surfactant administration(LISA) technique is a Important treatment in premature infants with RDS.	Procedure: less invasive surfactant administration(LISA); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Collaborators: First Affiliated Hospital Bengbu Medical College; The First Affiliated Hospital of University of Science and Technology of China; Anqing Municipal Hospital; Second Affiliated Hospital of Bengbu Medical College; Fuyang people's hospital; lixin people's hospital; The third people's hospital of bengbu; Huaibei coal general hospital; Bozhou people's hospital; Luan people's hospital; Huaibei maternal and child health hospital; Huainan maternal and child health hospital; Chizhou people's hospital; Xuancheng people's hospital; The affiliated hospital of wannan medical college; Tongling People's Hospital; Maanshan maternity and child care; Wuhu first people's hospital
• Investigators: Study Director: Pan jiahua, PhD, Director of pediatric department of the First Affiliated Hospital of University of Science and Technology of China

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: October 4, 2019
• First Submitted That Met QC Criteria: October 13, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): October 15, 2019
• Last Update Submitted That Met QC Criteria: October 13, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: preterm infants; INSURE; NRDS; LISA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Premature Birth; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: LISA2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No