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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS Infants

Intervention / Treatment
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* Other: Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 4 Months

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
Interventional Model Description: A randomized, clinical, parallel-group study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NCPAP group<br>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<br>* 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.<br>|
| Active Comparator: NIPPV group<br>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<br>* 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.<br>|

What is the study measuring?
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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 |