MISA to NRDS：a Multicenter Study in China

Study Overview
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Brief Summary
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BACKGROUND Treatment of neonatal respiratory distress syndrome 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. Continuous positive airway pressure (CPAP) or NIPPV (Non-invasive positive pressure ventilation) with surfactant but without intubation may work synergistically. This randomized trial investigated a minimal invasive surfactant administration (MISA). To test the hypothesis that MISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks' gestational age in very low birth weight infants. DESIGN, SETTING, AND PARTICIPANTS The Minimal Invasive Surfactant Administration (MISA) was a multicenter, randomized, clinical, parallel-group study conducted between July 1st, 2017, and November 30, 2018, in 8 level III neonatal intensive care units in Beijing, Tianjin, and Hebei province, China. The final follow-up date was March 30, 2019. Participants enrolled spontaneously breathing preterm infants born between 26.1 and 31.9 weeks' gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant (Calf pulmonary surfactant, Double-Crane Pharmaceutical Co., China) either via a 5Fr nasogastric tube during CPAP/NIPPV-assisted spontaneous breathing (minimal invasive surfactant administration group, MISA group) or after conventional endotracheal intubation during mechanical ventilation (endotracheal intubation surfactant administration group, EISA group). INTERVENTION MISA via a 5Fr nasogastric tube with an ophthalmic surgery straight forceps.

Official Title
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Minimal Invasive Surfactant Administration to Treat Neonatal Respiratory Distress Syndrome: a Multicenter Clinical Study in China

Conditions
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Bronchopulmonary Dysplasia, Patent Ductus Arteriosus, Intraventricular Hemorrhage, Necrotizing Enterocolitis, Periventricular Leukomalacia

Intervention / Treatment
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* Procedure: Minimal Invasive surfactant administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: preterm infants born before 32 weeks gestational age spontaneously breathing receiving continuous positive airway pressure (CPAP) or NIPPV (Non-invasive positive pressure ventilation) without intubation clinical diagnosis of respiratory distress syndrome. Exclusion Criteria: with obvious malformations with asphyxia requiring intubation during resuscitation need endotracheal intubation or mechanical ventilation before surfactant administration.

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: MISA group<br>minimal invasive surfactant administration group | Procedure: Minimal Invasive surfactant administration<br>* Participants enrolled spontaneously breathing preterm infants born between 26.1 and 31.9 weeks' gestational age with signs of respiratory distress syndrome. Preterm infants of the MISA (Minimal invasive surfactant administration) group were assigned to receive surfactant (Calf pulmonary surfactant, Double-Crane Pharmaceutical Co., China) via a 5Fr nasogastric tube with an ophthalmic surgery straight forceps during CPAP/NIPPV-assisted spontaneous breathing.<br>|
| No Intervention: EISA group<br>conventional treatment: endotracheal intubation surfactant administration group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bronchopulmonary dysplasia (BPD) | Number of very low birth weight preterm infants with BPD | At 36 weeks'gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of major complications | Number of very low birth weight preterm infants diagnosed with major complications (i.e.patent ductus arteriosus,pulmonary hemorrhage, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, and retinopathy of prematurity） | Through study completion and up to corrected three months |