NIV-MISA-NRDS Trial: a Multicenter Study in China

NCT05137340 | Terminated DMC

• 1 other identifier: M2021378
• Study Type: interventional
• Target: 312
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND Non-invasive ventilation (NIV) treatment have been developed to minimize lung damage and to avoid invasive mechanical ventilation (IMV) in preterm infants, especially in those with gestational age less than 30 weeks. Our hypothesis is that for preterm infants less than 30 weeks with potential to develop neonatal respiratory distress syndrome (NRDS), nasal continuous positive airway pressure (NCPAP) is non-inferior to the nasal intermittent positive pressure ventilation (NIPPV) as primary respiratory support before minimal invasive surfactant administration (MISA). DESIGN, SETTING, AND PARTICIPANTS The NIV-MISA-NRDS trial is planned as an unblinded, multicenter, randomized, non-inferiority trial at 11 tertiary care neonatal intensive care units in China. Eligible infants are preterm infants of 24 to 29+6 weeks' gestational age who have spontaneous breaths at birth and require primary NIV support for NRDS in the first 2 h of life. Infants are randomized 1:1 to treatment with either NCPAP or NIPPV once admitted into neonatal intensive care unit (NICU). If the patient with progressively aggravates respiratory distress and clinically diagnose as NRDS, pulmonary surfactant will be supplemented by minimal invasive surfactant administration (MISA) in the first 2 hours . MAIN OUTCOMES AND MEASURES The primary outcome is NIV treatment failure within 72 hours after birth, as determined by objective oxygenation, blood gas, and apnea criteria, or the need for intubation and mechanical ventilation. Secondary outcomes mainly include the incidence of complications during hospitalization . With a specified noninferiority margin of 10%, using a two-sided 95% CI and 80% power, the study requires 480 infants per group (total 960 infants in the study).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• NIV treatment failure 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

  From enrollment to the first 72 hours of life

Secondary Outcomes (16)

• NIV treatment failure within 7days after birth

  From enrollment to 7days after birth

• Rate of pneumothorax

  Through study completion and up to corrected three months

• Rate of pulmonary hemorrhage

  Through study completion and up to corrected three months

• Rate of hemodynamically significant patent ductus arteriosus (hsPDA)

  Through study completion and up to corrected three months

• Rate of intraventricular hemorrhages (IVH, grade III or Ⅳ)

  Through study completion and up to corrected three months

Study Arms (2)

NCPAP group

EXPERIMENTAL

The ventilator parameter of NCPAP group are set with positive end expiratory pressure \[PEEP\] of 6cmH2O (adjustment range 6-8cmH2O) and FiO2 of 0.21-0.40, in order to maintain an oxygen saturation level of 90%-95%.

Other: Nasal continuous positive airway pressure

NIPPV group

ACTIVE COMPARATOR

NIPPV group are set with PEEP of 6cmH2O (adjustment range 6-8cmH2O), peak inspiratory pressure \[PIP\] of 15cmH2O (regulation range 15-20cmH2O), inspiratory time of 0.3s (regulation range 0.3-0.4s), respiratory rate of 30 times/min (regulation range 20-40 times/min) and FiO2 of 0.21-0.40.

Other: Non-invasive positive pressure ventilation

Interventions

Nasal continuous positive airway pressure OTHER

Preterm infants with spontaneous breathing are stabilized on non-invasive respiratory support (PEEP of 6 cmH2O and FiO2≤0.40) in the delivery room and during admission to NICU, and then randomly selected to start NCPAP within 30 minutes of birth. Under NCPAP, the calf pulmonary surfactant will be administered via MISA method within 120 minutes after birth if infants are clinically diagnosed with RDS.

NCPAP group

Non-invasive positive pressure ventilation OTHER

Preterm infants with spontaneous breathing are stabilized on non-invasive respiratory support (PEEP of 6 cmH2O and FiO2≤0.40) in the delivery room and during admission to NICU, and then randomly selected to start NIPPV within 30 minutes of birth. Under NIPPV, the calf pulmonary surfactant will be administered via MISA method within 120 minutes after birth if infants are clinically diagnosed with RDS.

NIPPV group

Eligibility Criteria

• Age: 30 Minutes - 4 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants who meet all of the following criteria will be included:
• Infants of 24 to 29+6 weeks GA.
• Infants with spontaneous breathing and signs of respiratory distress will receive non-invasive respiratory support (PEEP of 6 cmH2O and fraction of inspired oxygen\[FiO2\]≤0.40) immediately after birth in the delivery room and during transfer to NICU. Once the infant is settled down in the incubator, and the ventilation support of NCPAP or NIPPV by ventilator in NICU will by started according to the randomization of protocol.
• Under NCPAP or NIPPV, the surfactant will be administered via MISA approach within 120 minutes after birth if the infant required FiO2\>0.3 for transcutaneous oxygen saturation \[SpO2\]\>85%, or Silverman Anderson Score \[SAS\] \>5 points or SAS increasing \>2 points per hour.
• Parental consent will be obtained for all participants.

You may not qualify if:

• Infants who meet any of the following criteria will be excluded:
• Infants who have been intubated prior to pulmonary surfactant administration due to postnatal resuscitation or other reasons.
• Infants with obvious malformations affecting respiratory function.
• Infants who have been transferred out to other hospitals for surgery or died for other complications with uncompleted data.
• Infants who have participated in other interventional researches.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, China

Location

Related Publications (1)

• 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.

  PMID: 35967549 DERIVED

MeSH Terms

Interventions

Continuous Positive Airway Pressure

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Xiaomei Tong, Tong,

  Peking University Third Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized, clinical, parallel-group study

Study Record Dates

• First Submitted: November 28, 2021
• First Posted: November 30, 2021
• Study Start: December 1, 2021
• Primary Completion: February 1, 2025
• Study Completion: March 10, 2025
• Last Updated: July 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)