to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm NeonatesNCT05141435
NHFOV as Primary Support in Very Preterm Infants With RDS
A study testing infants receive primary non-invasive respiratory support by mean of nCPAP and infants receive primary non-invasive respiratory support by mean of NHFOV in people with to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm Neonates, run by Jiulongpo No.1 People's Hospital at 3 sites in China.
Trial summary
This will be a prospective, multi-center, two-arms,parallel, randomized, controlled trial with a superiority design,conducted in China. The investigators conduct this multi-centre, randomized, controlled trial to test the hypothesis that NHFOV is more effective than nCPAP in the treatment of respiratory distress… Read more about this study
- Who is it for?
- Ages 0 to 2 hours
- Conditions the study is for
- to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm Neonates
- What is being tested?
- infants receive primary non-invasive respiratory support by mean of nCPAP and infants receive primary non-invasive respiratory support by mean of NHFOV
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 3 sitesChina
- Study dates
- 1 Aug 2022to 5 Aug 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 0 to 2 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age between 240/7 and 286/7 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and a fraction of inspired oxygen (FiO2) greater than 0.25 for target saturation of peripheral oxygen (SpO2) 89% to 94%；（3） Age less than 2 hours
Who cannot join
- Intubated forany reasons at birth
- Major congenital malformations or known complex congenital heart disease
- No parental consent
Trial locations and contacts
3 sites in 1 country.
China3 sites
Hunan Provincial Maternal and Child Health Care Hospital
Changsha, Hunan
The Second Hospital of Shandong University
Jinan, Shandong
Qujing Maternity and cChild Healthcare Hospital
Qujing, Yunnan
About this study
Official title: NHFOV vs nCPAP in Very Preterm Infants With Respiratory Distress Syndrome: A Multi-center, Prospective, Randomized, Controlled Clinical Superior Trial
This will be a prospective, multi-center, two-arms,parallel, randomized, controlled trial with a superiority design,conducted in China. The investigators conduct this multi-centre, randomized, controlled trial to test the hypothesis that NHFOV is more effective than nCPAP in the treatment of respiratory distress syndrome (RDS) in infants with a gestational age of less than 28 weeks when used as a primary noninvasive ventilation (NIV) mode.
Read the detailed description
Preterm infants are eligible to the study if they they match the following inclusion criteria: (1) Gestational age between 240/7 and 286/7 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and a fraction of inspired oxygen (FiO2) greater than 0.25 for target saturation of peripheral oxygen (SpO2) 89% to 94%;; (3) Age less than 2 hours; (4)Informed parental consent has been obtained.
Neonates will be randomized and assigned either to nCPAP or NHFOV arms with a 1:1ratio, when patients fulfill all inclusion criteria. Randomization cannot be done earlier. Simple randomization will be done according to a computer-generated random number table and will be posted in a specific secured website 24/7 available. Twins will be allocated in the same treatment group. Infants randomized to one arm cannot crossover to the other or vice- versa during the study. For all the groups, if the fraction of inspired oxygen (FiO2) requirement is persistently higher than 0.30 per target SpO2 89-94% after starting the respiratory support, newborns receive Surfactant by "LISA" technique, administration of surfactant (Curosurf,Chiesi Pharmaceutics, Parma, Italy) 200 mg/kg.
After the administration of surfactant, if FiO2 requirement is persistently >0.4 to keep SpO2 89-94% or severe apnea episodes are present (defined as recurrent apnea with >3 episodes/h associated with heart rate <100/min or a single episode of apnea requiring bag and mask ventilation within a 24-hour period ) or at the blood gas (arterial or free-flowing capillary blood) PaCO2>60 mmHg and potential of hydrogen (pH)<7.20 obtained at least 1 hour after commencement of the assigned treatment, newborns are intubated and mechanically ventilated.
For all the newborns enrolled in the study, arterial or free-flowing capillary blood gas is checked every 6-12 hours, a cerebral and cardiac ultrasound screening is performed within 24 hrs. Further controls follow the routine of the ward.
- Being tested
- infants receive primary non-invasive respiratory support by mean of nCPAP, infants receive primary non-invasive respiratory support by mean of NHFOV
- Keywords
- nasal high frequency oscillation ventilation(NHFOV); nasal continuous positive airway pressure(NCPAP); preterm infants
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
infants receive primary non-invasive respiratory support by mean of nCPAPProcedure or surgery
neonates assigned to the nCPAP group will be started on a pressure of 6 cmH2O( adjust range:6-10 cmH2O) , with FiO2 (0.21-0.40)adjusted to target SpO2 from 89% to 94%. CPAP will be provided by either variable flow or continuous flow devices, as there is no clear evidence that one type of CPAP generator would be better than any other by pure CPAP system.
infants receive primary non-invasive respiratory support by mean of NHFOVProcedure or surgery
neonates assigned to NHFOV will be started with the following boundaries: a) Paw of 6 cmH2O (the range 6-10 cmH2O); b) frequency of 10 Hz (the range 8-12 Hz). c) Inspiratory time 50% (1:1). d) amplitude 15 cmH2O(the range 15-25 cmH2O) NHFOV will only be provided with piston/ membrane oscillators able to provide an active expiratory phase (that is, Acutronic FABIAN-III, SLE 5000, Loweinstein Med LEONI+, Sensormedics 3100A).
| Study group | Role | What they receive |
|---|---|---|
| NCPAP | Active comparator | Not described Receives: Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP; Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV |
| NHFOV | Active comparator | Not described Receives: Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP; Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Failure Within 72 Hours After Randomization 72 Hours After Randomization Need for Invasive Mechanical Ventilation
The respiratory support failure will be considered if one of the following occurs: (1) severe respiratory acidosis (defined as PaCO2 >60mm Hg with pH<7.2) for at least 1hour; (2) hypoxia refractory to study intervention (defined as SpO2 <90%, with FiO2=0.4 and maximal pressures allowed in the study arm) for at least 1 hour after the administration of surfactant; (3) severe apnoea (defined as recurrent apnoea with >3 episodes/hour associated with heart rate <100/min or a single episode of apnoea requiring bag and mask ventilation) and (4) attending physician determined that urgent intubation is necessary.
Measured: within 72 hrs from the beginning of the study mode
Secondary outcomes (1)
Rate of Airleaks(Pneumothorax and/or Pneumomediastinum) Occurred During Noninvasive Respiratory Support
the diagnosis a Chest XR
Measured: the first 4weeks of life or until NICU discharge, whichever comes first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2021
- Study start1 Aug 2022
- Primary completion5 Aug 2024
- Study completion5 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm NeonatesStudies 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
- Masking
- None (open label)
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiulongpo No.1 People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Jiangxi Maternal and Child Health Hospital, Children's Hospital of Chongqing Medical University, Guiyang Maternity and Child Health Care Hospital, The Second Hospital of Shandong University, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Hunan Provincial Maternal and Child Health Care Hospital, Zhangzhou Affiliated Hospital of Fujian Medical University, Women and Children's Health Hospital of Yulin, Chongqing Three Gorges Central Hospital, Gansu Provincial Maternal and Child Health Care Hospital, The First People's Hospital of Yunnan, Chengdu Women's and Children's Central Hospital, Maternal and Children's Healthcare Hospital of Taian, People's Hospital of Xinjiang Uygur Autonomous Region, Quanzhou Children's Hospital, Chongqing West Hospital, Chongqing Medical Center for Women and Children, Xiamen Maternity & Child Care Hospital, Qujing Maternal and Child Health Hospital, Liuzhou Maternity and Child Healthcare Hospital, International Peace Maternity and Child Health Hospital
- Responsible party
- Principal investigator, Xingwang Zhu, Children's Hospital of Chongqing Medical University
- Investigators
- Yuan Shi, PhD, Study chair, Children's Hospital of Chongqing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05141435
- Sponsor's protocol ID
- NHFOV prevent intubation
- Status last verified
- Jul 2025
- First submitted
- 19 Nov 2021
- Last updated
- 24 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Li Y, Zhu X, Li LJ, Chen L, Yang Q, Xu L, Liang W, Lin X, Li C, Xue J, Liu L, Pan X, Ju R, Peng X, Tang W, Shi Y; NHFOV study group. Non-invasive high frequency oscillatory ventilation for primary respiratory support in extremely preterm infants: multicentre randomised controlled trial. BMJ. 2025 Oct 6;391:e085569. doi: 10.1136/bmj-2025-085569.
PubMed 41052898Li Y, Zhu X, Shi Y; Noninvasive High-Frequency Oscillatory Ventilation Study Group. Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in extremely preterm infants with respiratory distress syndrome: study protocol for a multicentre randomised controlled, superiority trial. BMJ Open. 2023 Mar 3;13(3):e068450. doi: 10.1136/bmjopen-2022-068450.
PubMed 36868587
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NHFOV vs nCPAP in Very Preterm Infants With Respiratory Distress Syndrome: A Multi-center, Prospective, Randomized, Controlled Clinical Superior Trial
- ClinicalTrials.gov ID
- NCT05141435
- Acronym / sponsor ID
- NHFOV prevent intubation
- Keywords
- nasal high frequency oscillation ventilation(NHFOV); nasal continuous positive airway pressure(NCPAP); preterm infants
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 360 participants (actual)
- Lead sponsor
- Jiulongpo No.1 People's HospitalUniversity, hospital or other
- Collaborators
- Jiangxi Maternal and Child Health Hospital, Children's Hospital of Chongqing Medical University, Guiyang Maternity and Child Health Care Hospital, The Second Hospital of Shandong University, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Hunan Provincial Maternal and Child Health Care Hospital, Zhangzhou Affiliated Hospital of Fujian Medical University, Women and Children's Health Hospital of Yulin, Chongqing Three Gorges Central Hospital, Gansu Provincial Maternal and Child Health Care Hospital, The First People's Hospital of Yunnan, Chengdu Women's and Children's Central Hospital, Maternal and Children's Healthcare Hospital of Taian, People's Hospital of Xinjiang Uygur Autonomous Region, Quanzhou Children's Hospital, Chongqing West Hospital, Chongqing Medical Center for Women and Children, Xiamen Maternity & Child Care Hospital, Qujing Maternal and Child Health Hospital, Liuzhou Maternity and Child Healthcare Hospital, International Peace Maternity and Child Health Hospital
- Study start
- 1 Aug 2022 (actual)
- Primary completion
- 5 Aug 2024 (actual)
- Study completion
- 5 Aug 2024 (actual)
- First posted
- 2 Dec 2021 (actual)
- Results
- Posted 10 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a prospective, multi-center, two-arms,parallel, randomized, controlled trial with a superiority design,conducted in China. The investigators conduct this multi-centre, randomized, controlled trial to test the hypothesis that NHFOV is more effective than nCPAP in the treatment of respiratory distress syndrome (RDS) in infants with a gestational age of less than 28 weeks when used as a primary noninvasive ventilation (NIV) mode.
Detailed description
Preterm infants are eligible to the study if they they match the following inclusion criteria: (1) Gestational age between 240/7 and 286/7 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and a fraction of inspired oxygen (FiO2) greater than 0.25 for target saturation of peripheral oxygen (SpO2) 89% to 94%;; (3) Age less than 2 hours; (4)Informed parental consent has been obtained.
Neonates will be randomized and assigned either to nCPAP or NHFOV arms with a 1:1ratio, when patients fulfill all inclusion criteria. Randomization cannot be done earlier. Simple randomization will be done according to a computer-generated random number table and will be posted in a specific secured website 24/7 available. Twins will be allocated in the same treatment group. Infants randomized to one arm cannot crossover to the other or vice- versa during the study. For all the groups, if the fraction of inspired oxygen (FiO2) requirement is persistently higher than 0.30 per target SpO2 89-94% after starting the respiratory support, newborns receive Surfactant by "LISA" technique, administration of surfactant (Curosurf,Chiesi Pharmaceutics, Parma, Italy) 200 mg/kg.
After the administration of surfactant, if FiO2 requirement is persistently >0.4 to keep SpO2 89-94% or severe apnea episodes are present (defined as recurrent apnea with >3 episodes/h associated with heart rate <100/min or a single episode of apnea requiring bag and mask ventilation within a 24-hour period ) or at the blood gas (arterial or free-flowing capillary blood) PaCO2>60 mmHg and potential of hydrogen (pH)<7.20 obtained at least 1 hour after commencement of the assigned treatment, newborns are intubated and mechanically ventilated.
For all the newborns enrolled in the study, arterial or free-flowing capillary blood gas is checked every 6-12 hours, a cerebral and cardiac ultrasound screening is performed within 24 hrs. Further controls follow the routine of the ward.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NCPAP | Active comparator | Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP, Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV |
| NHFOV | Active comparator | Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP, Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV |
Who may qualify
- Ages
- 0 to 2 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Gestational age between 240/7 and 286/7 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and a fraction of inspired oxygen (FiO2) greater than 0.25 for target saturation of peripheral oxygen (SpO2) 89% to 94%；（3） Age less than 2 hours
Key exclusion criteria (3 listed)
- Intubated forany reasons at birth
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 |
|---|---|---|
| infants receive primary non-invasive respiratory support by mean of nCPAPneonates assigned to the nCPAP group will be started on a pressure of 6 cmH2O( adjust range:6-10 cmH2O) , with FiO2 (0.21-0.40)adjusted to target SpO2 from 89% to 94%. CPAP will be provided by either variable flow or continuous flow devices, as there is no clear evidence that one type of CPAP generator would be better than any other by pure CPAP system. | Procedure or surgery | NCPAP, NHFOV |
| infants receive primary non-invasive respiratory support by mean of NHFOVneonates assigned to NHFOV will be started with the following boundaries: a) Paw of 6 cmH2O (the range 6-10 cmH2O); b) frequency of 10 Hz (the range 8-12 Hz). c) Inspiratory time 50% (1:1). d) amplitude 15 cmH2O(the range 15-25 cmH2O) NHFOV will only be provided with piston/ membrane oscillators able to provide an active expiratory phase (that is, Acutronic FABIAN-III, SLE 5000, Loweinstein Med LEONI+, Sensormedics 3100A). | Procedure or surgery | NCPAP, NHFOV |
Primary outcome
Treatment Failure Within 72 Hours After Randomization 72 Hours After Randomization Need for Invasive Mechanical Ventilation
Time frame: within 72 hrs from the beginning of the study mode
The respiratory support failure will be considered if one of the following occurs: (1) severe respiratory acidosis (defined as PaCO2 >60mm Hg with pH<7.2) for at least 1hour; (2) hypoxia refractory to study intervention (defined as SpO2 <90%, with FiO2=0.4 and maximal pressures allowed in the study arm) for at least 1 hour after the administration of surfactant; (3) severe apnoea (defined as recurrent apnoea with >3 episodes/hour associated with heart rate <100/min or a single episode of apnoea requiring bag and mask ventilation) and (4) attending physician determined that urgent intubation is necessary.
1 secondary outcome
Rate of Airleaks(Pneumothorax and/or Pneumomediastinum) Occurred During Noninvasive Respiratory Support
Time frame: the first 4weeks of life or until NICU discharge, whichever comes first
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41052898Li Y, Zhu X, Li LJ, Chen L, Yang Q, Xu L, Liang W, Lin X, Li C, Xue J, Liu L, Pan X, Ju R, Peng X, Tang W, Shi Y; NHFOV study group. Non-invasive high frequency oscillatory ventilation for primary respiratory support in extremely preterm infants: multicentre randomised controlled trial. BMJ. 2025 Oct 6;391:e085569. doi: 10.1136/bmj-2025-085569.
- Derived from this study: PubMed 36868587Li Y, Zhu X, Shi Y; Noninvasive High-Frequency Oscillatory Ventilation Study Group. Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in extremely preterm infants with respiratory distress syndrome: study protocol for a multicentre randomised controlled, superiority trial. BMJ Open. 2023 Mar 3;13(3):e068450. doi: 10.1136/bmjopen-2022-068450.
- Individual participant dataSharing planned: Yes
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.
Yuan Shi, PhD study chair
Children's Hospital of Chongqing Medical University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing infants receive primary non-invasive respiratory support by mean of nCPAP and infants receive primary non-invasive respiratory support by mean of NHFOV in people with to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm Neonates, run by Jiulongpo No.1 People's Hospital at 3 sites 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 1 inclusion and 3 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: finished, as of the sponsor's last update on 24 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 3 sites 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?
Yes. Results are posted in the registry (first posted 10 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Treatment Failure Within 72 Hours After Randomization 72 Hours After Randomization Need for Invasive Mechanical Ventilation (time frame: within 72 hrs from the beginning of the study mode). 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 NCT05141435, 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 24 Jul 2025.