Clinical trial NCT05137340: NIV-MISA-NRDS Trial: a Multicenter Study in China
Official title: Nasal Continuous Positive Airway Pressure Versus Non-invasive Positive Pressure Ventilation as Primary Support Before Minimally Invasive Surfactant Administration for Preterm Infants With NRDS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS Infants
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
First posted: 2021-11-30
Enrollment: 312
Sex: ALL
Minimum age (years): 30
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, clinical, parallel-group study
Primary purpose: TREATMENT

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 14 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).

Detailed description: 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%.

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.

Eligibility criteria: Inclusion Criteria

Infants who meet all of the following criteria will be included:

1. Infants of 24 to 29+6 weeks GA.
2. 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.
3. 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.
4. Parental consent will be obtained for all participants.

Exclusion Criteria

Infants who meet any of the following criteria will be excluded:

1. Infants who have been intubated prior to pulmonary surfactant administration due to postnatal resuscitation or other reasons.
2. Infants with obvious malformations affecting respiratory function.
3. Infants who have been transferred out to other hospitals for surgery or died for other complications with uncompleted data.
4. Infants who have participated in other interventional researches.

Primary outcomes:
measure: NIV treatment failure within the first 72 hours of life
timeFrame: From enrollment to the first 72 hours of life
Secondary outcomes:
measure: NIV treatment failure within 7days after birth
timeFrame: From enrollment to 7days after birth
measure: Rate of pneumothorax
timeFrame: Through study completion and up to corrected three months
measure: Rate of pulmonary hemorrhage
timeFrame: Through study completion and up to corrected three months
measure: Rate of hemodynamically significant patent ductus arteriosus (hsPDA)
timeFrame: Through study completion and up to corrected three months
measure: Rate of intraventricular hemorrhages (IVH, grade III or Ⅳ)
timeFrame: Through study completion and up to corrected three months
measure: Rate of periventricular leukomalacia
timeFrame: Through study completion and up to corrected three months
measure: Rate of late-onset sepsis
timeFrame: Through study completion and up to corrected three months
measure: Rate of bronchopulmonary dysplasia (BPD)
timeFrame: At 36 weeks PMA
measure: Rate of necrotizing enterocolitis (NEC)
timeFrame: Through study completion and up to corrected three months
measure: Rate of retinopathy of prematurity (ROP)
timeFrame: Through study completion and up to corrected three months
measure: Duration of non-invasive ventilation, IMV, and supplemental oxygen
timeFrame: Through study completion and up to corrected three months
measure: Length of hospital stay
timeFrame: From enrollment to the end of treatment at an average of 8 weeks
measure: Required>1 doses of surfactant
timeFrame: From enrollment to 5 days after birth
measure: In-hospital mortality
timeFrame: Through study completion and up to corrected three months
measure: Pneumonia
timeFrame: Through study completion and up to corrected three months
measure: Persistent pulmonary hypertension of newborn
timeFrame: Through study completion and up to corrected three months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Third Hospital
Study officials:
affiliation: Peking University Third Hospital
name: Xiaomei Tong, Tong,
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.