NCPAP+MISA vs. NIPPV+MISA to NRDS：a Multicenter Randomized Study

Minimally Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes for the Treatment of Respiratory Distress Syndrome in Premature Infants: a Multicenter Prospective Randomized Controlled Study

BACKGROUND Treatment of neonatal respiratory distress syndrome(NRDS) with exogenous surfactant and mechanical ventilation made millions of preterm infants survived in neonatal intensive care unit (NICU). Endotracheal intubation surfactant administration is related to invasive intubation and short periods of positive pressure ventilation and implies the risk of lung injury.Recent studies have shown that minimally invasive surfactant administration(MISA) has more advantages than endotracheal intubation in premature infants with NRDS with spontaneous breathing (especially those with gestational age less than 30 weeks). It can reduce the time of invasive mechanical ventilation and reduce the incidence of bronchopulmonary dysplasia.The purpose of this study was to compare the efficacy of MISA in the treatment of NRDS in premature infants under the initial respiratory support mode of nasal continuous positive airway pressure(NCPAP) and Non-invasive positive pressure ventilation (NIPPV).

DESIGN, SETTING, AND PARTICIPANTS The study was a multicenter, randomized, clinical, parallel-group study conducted between December 1st, 2021, and August 30,2023, in 16 level III neonatal intensive care units in China.Participants enrolled spontaneously breathing preterm infants born between 24 and 29.9 weeks' gestational age with signs of respiratory distress syndrome. After transfer to NICU ward, infants were randomly assigned to NCPAP group and NIPPV group.Patients diagnosed with NRDS on non-invasive respiratory support (NIPPV or NCPAP) were given a therapeutic dose of pulmonary surfactant via MISA within 120 minutes after birth.

Study Overview

• Status: Recruiting
• Conditions: Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS Infants
• Intervention / Treatment: Other: Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation

Detailed Description

NCPAP group ventilator parameter setting: PEEP 6cmH2O (adjustment range 6-8cmH2O), FiO2 adjustment range 0.21-0.40, in order to achieve postnatal target oxygen saturation. The initial ventilator parameters of NIPPV group were as follows: PEEP 6cmH2O (adjustment range 6-8cmH2O), PIP15cmH2O (regulation range 15-20cmH2O), inspiratory time 0.3s (regulation range 0.3-0.4s), respiratory rate 30 beats/min (regulation range 20-40 beats/min), and FiO2 regulation range 0.21-0.40 in order to achieve postnatal target oxygen saturation.

• Study Type: Interventional
• Enrollment (Anticipated): 960
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tongyan Han, MD; Phone Number: 13520695016; Email: tongyanhan@qq.com
• Study Contact Backup: Name: Hui Zhang, MD; Phone Number: 15201304304; Email: zhanghui19880224@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Tongyan Han, MD; Phone Number: 13520695016; Email: tongyanhan@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 4 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Participants enrolled spontaneously breathing preterm infants born between 24 and 29.9 weeks' gestational age with signs of respiratory distress syndrome.Preterm infants were receiving nasal continuous positive airway pressure(NCPAP) or non-invasive positive pressure ventilation (NIPPV) without intubation before surfactant administration. Patients diagnosed with NRDS on non-invasive respiratory support (NIPPV or NCPAP) were given a therapeutic dose of pulmonary surfactant via MISA within 120 minutes after birth. Parental consent was obtained for all participants before birth.

Exclusion Criteria:(1) Preterm infants who had been intubated prior to pulmonary surfactant administration due to postnatal resuscitation or other reasons; (2) preterm infants with obvious malformations; (3)Newborns who died or were transferred to other hospitals for surgery or whose information was incomplete;(4)Infants who participated in other interventional research projects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NCPAP group; Participants enrolled spontaneously breathing preterm infants born between 24 and 29.9 weeks' gestational age with signs of respiratory distress syndrome. The initial respiratory support mode of premature infants assigned to NCPAP group was NCPAP. Patients diagnosed with NRDS on NCPAP were given a therapeutic dose of pulmonary surfactant via MISA within 120 minutes after birth. NCPAP group ventilator parameter setting: PEEP 6cmH2O (adjustment range 6-8cmH2O), FiO2 adjustment range 0.21-0.40, in order to achieve postnatal target oxygen saturation.	Other: Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation; After transfer to NICU ward, infants were randomly assigned to NCPAP group and NIPPV group. Patients diagnosed with NRDS on non-invasive respiratory support (NIPPV or NCPAP) were given a therapeutic dose of pulmonary surfactant via MISA within 120 minutes after birth.
ACTIVE_COMPARATOR: NIPPV group; Participants enrolled spontaneously breathing preterm infants born between 24 and 29.9 weeks' gestational age with signs of respiratory distress syndrome. The initial respiratory support mode of premature infants assigned to NIPPV group was NIPPV. Patients diagnosed with NRDS on NIPPV were given a therapeutic dose of pulmonary surfactant via MISA within 120 minutes after birth. The initial ventilator parameters of NIPPV group were as follows: PEEP 6cmH2O (adjustment range 6-8cmH2O), PIP15cmH2O (regulation range 15-20cmH2O), inspiratory time 0.3s (regulation range 0.3-0.4s), respiratory rate 30 beats/min (regulation range 20-40 beats/min), and FiO2 regulation range 0.21-0.40 in order to achieve postnatal target oxygen saturation.	Other: Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation; After transfer to NICU ward, infants were randomly assigned to NCPAP group and NIPPV group. Patients diagnosed with NRDS on non-invasive respiratory support (NIPPV or NCPAP) were given a therapeutic dose of pulmonary surfactant via MISA within 120 minutes after birth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The need for intubation within the first 72 hours of life	The failure of non-invasive nasal respiratory support(NIPPV or NCPAP)	Within the first 72 hours of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decreased morbidity of bronchopulmonary dysplasia (BPD)	Preterm infants were survived without BPD at 36 weeks' gestational age	At 36 weeks'gestational age

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Investigators: Principal Investigator: Xiaomei Tong, Tong,, Peking University Third Hospital

Publications and helpful links

General Publications

• Zhang H, Li J, Zeng L, Gao Y, Zhao W, Han T, Tong X. A multicenter, randomized controlled, non-inferiority trial, comparing nasal continuous positive airway pressure with nasal intermittent positive pressure ventilation as primary support before minimally invasive surfactant administration for preterm infants with respiratory distress syndrome (the NIV-MISA-RDS trial): Study protocol. Front Pediatr. 2022 Jul 29;10:968462. doi: 10.3389/fped.2022.968462. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2021
• Primary Completion (ANTICIPATED): June 30, 2023
• Study Completion (ANTICIPATED): August 31, 2023

Study Registration Dates

• First Submitted: November 28, 2021
• First Submitted That Met QC Criteria: November 28, 2021
• First Posted (ACTUAL): November 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 30, 2021
• Last Update Submitted That Met QC Criteria: November 28, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: M2021378

Drug and device information, study documents

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