MISA to NRDS：a Multicenter Study in China

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

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.

Study Overview

• Status: Completed
• Conditions: Necrotizing Enterocolitis; Intraventricular Hemorrhage; Bronchopulmonary Dysplasia; Patent Ductus Arteriosus; Periventricular Leukomalacia
• Intervention / Treatment: Procedure: Minimal Invasive surfactant administration

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital

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:

1. preterm infants born before 32 weeks gestational age
2. spontaneously breathing receiving continuous positive airway pressure (CPAP) or NIPPV (Non-invasive positive pressure ventilation) without intubation
3. clinical diagnosis of respiratory distress syndrome.

Exclusion Criteria:

1. with obvious malformations
2. with asphyxia requiring intubation during resuscitation
3. need endotracheal intubation or mechanical ventilation before surfactant administration.

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: MISA group; minimal invasive surfactant administration group	Procedure: Minimal Invasive surfactant administration; 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.
NO_INTERVENTION: EISA group; conventional treatment: endotracheal intubation surfactant administration group

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ACTUAL): November 30, 2018
• Study Completion (ACTUAL): March 30, 2019

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: August 31, 2019
• First Posted (ACTUAL): September 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 4, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Lung Diseases; Congenital Abnormalities; Gastrointestinal Diseases; Infant, Newborn, Diseases; Gastroenteritis; Intestinal Diseases; Lung Injury; Heart Defects, Congenital; Cardiovascular Abnormalities; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Encephalomalacia; Hemorrhage; Enterocolitis; Enterocolitis, Necrotizing; Bronchopulmonary Dysplasia; Ductus Arteriosus, Patent; Leukomalacia, Periventricular; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: M2017160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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