Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS InfantsNCT05137340
NIV-MISA-NRDS Trial: a Multicenter Study in China
A study testing Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation in people with Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS Infants, run by Peking University Third Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 minutes to 4 months
- Conditions the study is for
- Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS Infants
- What is being tested?
- Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 312 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2021to 10 Mar 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 minutes to 4 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the 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.
- Being tested
- Nasal continuous positive airway pressure, Non-invasive positive pressure ventilation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nasal continuous positive airway pressureOther
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.
Non-invasive positive pressure ventilationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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%. Receives: 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. Receives: Other: Non-invasive positive pressure ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From enrollment to the first 72 hours of life
Secondary outcomes (16)
NIV treatment failure within 7days after birth
The failure of non-invasive nasal respiratory support(NIPPV or NCPAP) within 7days after birth
Measured: From enrollment to 7days after birth
Rate of pneumothorax
Rate of pneumothorax
Measured: Through study completion and up to corrected three months
Rate of pulmonary hemorrhage
Rate of pulmonary hemorrhage
Measured: Through study completion and up to corrected three months
Rate of hemodynamically significant patent ductus arteriosus (hsPDA)
Rate of hemodynamically significant patent ductus arteriosus (hsPDA)
Measured: Through study completion and up to corrected three months
Rate of intraventricular hemorrhages (IVH, grade III or Ⅳ)
Rate of intraventricular hemorrhages (IVH, grade III or Ⅳ)
Measured: Through study completion and up to corrected three months
Rate of periventricular leukomalacia
Rate of periventricular leukomalacia
Measured: Through study completion and up to corrected three months
Rate of late-onset sepsis
Rate of late-onset sepsis
Measured: Through study completion and up to corrected three months
Rate of bronchopulmonary dysplasia (BPD)
Rate of bronchopulmonary dysplasia (BPD)
Measured: At 36 weeks PMA
Rate of necrotizing enterocolitis (NEC)
Rate of necrotizing enterocolitis (NEC)
Measured: Through study completion and up to corrected three months
Rate of retinopathy of prematurity (ROP)
Rate of retinopathy of prematurity (ROP)
Measured: Through study completion and up to corrected three months
Duration of non-invasive ventilation, IMV, and supplemental oxygen
Duration of non-invasive ventilation, duration of IMV, and days on supplemental oxygen
Measured: Through study completion and up to corrected three months
Length of hospital stay
Length of hospital stay
Measured: From enrollment to the end of treatment at an average of 8 weeks
Required>1 doses of surfactant
rate of required>1 doses of surfactant
Measured: From enrollment to 5 days after birth
In-hospital mortality
In-hospital mortality
Measured: Through study completion and up to corrected three months
Pneumonia
rate of pneumonia
Measured: Through study completion and up to corrected three months
Persistent pulmonary hypertension of newborn
rate of persistent pulmonary hypertension of newborn
Measured: Through study completion and up to corrected three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2021
- Study start1 Dec 2021
- Primary completion1 Feb 2025
- Study completion10 Mar 2025
Why it stopped: The trial was terminated early based on interim analysis results indicating futility. The decision was approved by the Data Safety Monitoring Committee (DSMC).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS InfantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, clinical, parallel-group study
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 312 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xiaomei Tong, Tong,, Principal investigator, Peking University Third Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05137340
- Sponsor's protocol ID
- M2021378
- Status last verified
- May 2025
- First submitted
- 28 Nov 2021
- Last updated
- 9 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhang H, Zhang Y, Zeng L, Tong X, Piao M, He H, Zhao C, Xie H, Zheng Z, Cui Q, Lai Y, Wang H, Wang L, Liu H, Tian X, Wu H, Kang L, Han T. Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation in Preterm Infants With Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA Netw Open. 2026 Jun 1;9(6):e2619785. doi: 10.1001/jamanetworkopen.2026.19785.
PubMed 42377961Zhang 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.
PubMed 35967549
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05137340
- Acronym / sponsor ID
- M2021378
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was terminated early based on interim analysis results indicating futility. The decision was approved by the Data Safety Monitoring Committee (DSMC).
- Enrolment
- 312 participants (actual)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 1 Feb 2025 (actual)
- Study completion
- 10 Mar 2025 (actual)
- First posted
- 30 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, clinical, parallel-group study
| Arm | Type | Receives |
|---|---|---|
| NCPAP group | Experimental | Other: Nasal continuous positive airway pressureThe 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 | Active comparator | Other: Non-invasive positive pressure ventilationNIPPV 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. |
Who may qualify
- Ages
- 30 minutes to 4 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nasal continuous positive airway pressurePreterm 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. | Other | NCPAP group |
| Non-invasive positive pressure ventilationPreterm 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. | Other | NIPPV group |
Primary outcome
NIV treatment failure within the first 72 hours of life
Time frame: From enrollment to the first 72 hours of life
The failure of non-invasive nasal respiratory support(NIPPV or NCPAP) within the first 72 hours of life
16 secondary outcomes
NIV treatment failure within 7days after birth
Time frame: From enrollment to 7days after birth
Rate of pneumothorax
Time frame: Through study completion and up to corrected three months
Rate of pulmonary hemorrhage
Time frame: Through study completion and up to corrected three months
Rate of hemodynamically significant patent ductus arteriosus (hsPDA)
Time frame: Through study completion and up to corrected three months
Rate of intraventricular hemorrhages (IVH, grade III or Ⅳ)
Time frame: Through study completion and up to corrected three months
Rate of periventricular leukomalacia
Time frame: Through study completion and up to corrected three months
Rate of late-onset sepsis
Time frame: Through study completion and up to corrected three months
Rate of bronchopulmonary dysplasia (BPD)
Time frame: At 36 weeks PMA
Rate of necrotizing enterocolitis (NEC)
Time frame: Through study completion and up to corrected three months
Rate of retinopathy of prematurity (ROP)
Time frame: Through study completion and up to corrected three months
Duration of non-invasive ventilation, IMV, and supplemental oxygen
Time frame: Through study completion and up to corrected three months
Length of hospital stay
Time frame: From enrollment to the end of treatment at an average of 8 weeks
Required>1 doses of surfactant
Time frame: From enrollment to 5 days after birth
In-hospital mortality
Time frame: Through study completion and up to corrected three months
Pneumonia
Time frame: Through study completion and up to corrected three months
Persistent pulmonary hypertension of newborn
Time frame: Through study completion and up to corrected three months
Results and safety
The study was stopped early (reason given: The trial was terminated early based on interim analysis results indicating futility. The decision was approved by the Data Safety Monitoring Committee (DSMC).). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2025.
- Derived from this study: PubMed 42377961Zhang H, Zhang Y, Zeng L, Tong X, Piao M, He H, Zhao C, Xie H, Zheng Z, Cui Q, Lai Y, Wang H, Wang L, Liu H, Tian X, Wu H, Kang L, Han T. Nasal Continuous Positive Airway Pressure vs Nasal Intermittent Positive Pressure Ventilation in Preterm Infants With Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA Netw Open. 2026 Jun 1;9(6):e2619785. doi: 10.1001/jamanetworkopen.2026.19785.
- Derived from this study: PubMed 35967549Zhang 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaomei Tong, Tong, principal investigator
Peking University Third Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nasal continuous positive airway pressure and Non-invasive positive pressure ventilation in people with Minimal Invasive Surfactant Administration in Two Different Non-invasive Ventilation Modes to NRDS Infants, run by Peking University Third Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The trial was terminated early based on interim analysis results indicating futility. The decision was approved by the Data Safety Monitoring Committee (DSMC).). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NIV treatment failure within the first 72 hours of life (time frame: From enrollment to the first 72 hours of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05137340, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.