Preterm InfantsNCT03099694
NHFOV vs. NCPAP as a Primary Treatment to Neonatal Respiratory Distress Syndrome(NRDS)
A study testing noninvasive high-frequency ventilation (nHFOV) and nasal continuous positive airway pressure (nCPAP) in people with Preterm Infants, run by Xingwang Zhu at 1 site in China.
Trial summary
The investigators compared advantages and disadvantages of two forms of noninvasive respiratory support -noninvasive high-frequency oscillatory ventilation (nHFOV) or nasal continuous positive airway pressure (nCPAP) -as a primary mode of ventilation in premature infants with RDS． Read more about this study
- Who is it for?
- Ages Up to 12 hours
- Conditions the study is for
- Preterm Infants
- What is being tested?
- noninvasive high-frequency ventilation (nHFOV) and nasal continuous positive airway pressure (nCPAP)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 340 participants
- Where
- 1 siteChina
- Study dates
- 27 Apr 2017to 28 Jul 2018
- 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 Up to 12 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- (1)Gestational age (GA) is from 26 to 34 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and chest X-ray findings; (3) RDS Silverman score>5; (4) informed parental consent has been obtained.
Who cannot join
- severe RDS requiring early intubation according to the American Academy of Pediatrics guidelines for neonatal resuscitation7; (2)major congenital malformations or complex congenital heart disease; (3) group B hemolytic streptococcus pneumonia, septicemia, pneumothorax, pulmonary hemorrhage; (4) cardiopulmonary arrest needing prolonged resuscitation; (5) transferred out of the NICUs without treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Noninvasive Ventilation for Preterm Neonates With Respiratory Distress Syndrome: a Multi-center Randomized Controlled Trial
The investigators compared advantages and disadvantages of two forms of noninvasive respiratory support -noninvasive high-frequency oscillatory ventilation (nHFOV) or nasal continuous positive airway pressure (nCPAP) -as a primary mode of ventilation in premature infants with RDS．
Read the detailed description
Background: Invasive mechanical ventilation is associated with development of adverse pulmonary and non-pulmonary outcomes in very low birth weight infants. Various modes of non-invasive respiratory support are being increasingly used to minimize the incidence of bronchopulmonary dysplasia (BPD). The aim of this trials to compare the effect of noninvasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary noninvasive ventilation support mode.
Methods/Design:In this multicenter, randomized, controlled trial, 300 preterm infants at gestational age (GA) less than 34 weeks with a diagnosis of RDS will be randomized to NHFOV or NCPAP as a primary mode of non-invasive respiratory support. Study will be conducted in 18 tertiary neonatal intensive care units in China.
The primary outcome is the need for invasive mechanical ventilation (IMV)during the first 7 days after enrollment in preterm infants randomized to the two groups. The secondary outcomes include days of hospitalization, days on noninvasive respiratory support, days on IMV, days on supplemental oxygen, mortality, need for surfactant, incidence of retinopathy of prematurity(ROP) and bronchopulmonary dysplasia(BPD), occurrence of abdominal distention, air leaks, intraventricular hemorrhage (IVH ≥ grade 3) and necrotizing enterocolitis (NEC> II stage). Other secondary outcomes include scores of Bayley Scales of Infant Development at 2 months and 2 years of corrected age.
- Conditions
- Preterm Infants
- Being tested
- noninvasive high-frequency ventilation (nHFOV), nasal continuous positive airway pressure (nCPAP)
- Keywords
- NRDS, nHFOV, nCPAP, preterm infants
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
noninvasive high-frequency ventilation (nHFOV)Procedure or surgery
NHFOV will be provided by a high frequency ventilator (CNO, Medin, Germany or SLE 5000, UK). NHFOV will be provided via binasal prongs.
nasal continuous positive airway pressure (nCPAP)Procedure or surgery
Infants assigned to the NCPAP group will be started on a pressure of 6 cmH2O (range: 6-8 cmH2O) by CPAP system (CNO Medin, Germany, Carefusion, USA)
| Study group | Role | What they receive |
|---|---|---|
| nCPAP | Active comparator | nasal continuous positive airway pressure (nCPAP) - as a primary mode of ventilation in premature infants with RDS Receives: Procedure: nasal continuous positive airway pressure (nCPAP) |
| nHFOV | Experimental | noninvasive high-frequency ventilation (nHFOV) as a primary mode of ventilation in premature infants with RDS Receives: Procedure: noninvasive high-frequency ventilation (nHFOV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Required Intubation
The criteria for endotracheal mechanical ventilation were as follows: severe respiratory acidosis (PaCO2 > 60 mmHg with pH<7.20), severe apnea and bradycardia (defined as recurrent apnea with > 3 episodes per hour associated with heart rate < 100/min, a single episode of apnea that required bag and mask ventilation), hypoxia (FiO2>0.5 with PaO2<50mmHg), severe respiratory distress, neonatal pulmonary hemorrhage, and cardiopulmonary arrest without effective resuscitation needing continued ventilation and rescue
Measured: during the first 7 days after birth
Secondary outcomes (12)
the Incidence of Intraventricular Hemorrhage (IVH, ≥ Grade Ⅲ)
The criteria for intraventricular hemorrhage (IVH, ≥ grade Ⅲ): intraventricular hemorrhage with ventricular dilatation and intraventricular hemorrhage with paren- ehymal hemorrhage. Intraventricular hemorrhage (≥ grade Ⅲ) is worse outcome.
Measured: first two months after birth
the Incidence of Pneumothorax
the incidence of pneumothorax
Measured: during non-invasive ventilation, up to 7 days
the Incidence of Neonatal Necrotizing Enterocolitis(>Stage II)
The criteria for neonatal necrotizing enterocolitis(>stage II): Unequivocal malfunction of the gastrointestinal tract is demonstrated clinically and by radiographic evaluation. Other disorders such as malrotation and volvulus and Hirschsprung's disease must be excluded.
Neonatal necrotizing enterocolitis(>stage II) is worse outcome
Measured: during non-invasive ventilation, up to 7 days
the Incidence of Retinopathy of Prematurity (>Stage II)
The criteria for Retinopathy of prematurity (>Stage II); extraretinal fibrovascular proliferation neovascularization extends from ridge into the vitreous. Retinopathy of prematurity (>Stage II) is worse outcome.
Measured: at a post-menstrual age of 36 weeks or at discharge
The Score of Bayley Scales of Infant Development
scores of Bayley Scales of Infant Development at 2 months old and 2 years old
Measured: 30 months
the Incidence of Bronchopulmonary Dysplasia(BPD)
BPD was defined according to the National Institutes of Health consensus definition: Need for O2 supplementation(FiO2>0.21) for at least 28 days after birth.
BPD is worse outcome.
Measured: at a post-menstrual age of 36 weeks or at discharge
the Incidence of Abdominal Distention
Abdominal circumference increase 2 centimeter during non-invasive ventilation
Measured: during non-invasive ventilation, up to 7 days
The Time of Non-invasive Ventilation
Hours
Measured: during non-invasive ventilation, up to 30 days
Length of Hospitalization
Days
Measured: during hospitalization, up to 60 days
Predischarge Mortality
Measured: during hospitalization, up to 60 days
Length of O2 Therapy
Days
Measured: during hospitalization, up to 60 days
Number of Participants With Thick Secretions Causing an Airway Obstruction
determined by the clinician
Measured: during non-invasive ventilation, up to 15 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start27 Apr 2017
- Primary completion28 Jul 2018
- Study completion28 Jul 2018
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 Preterm 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
- Masking
- None (open label)
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xingwang Zhu
- Sponsor type
- University, hospital or other
- Collaborators
- Guiyang Maternity and Child Health Care Hospital, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University, Children's Hospital of Chongqing Medical University, Chongqing Maternal and Child Health Hospital, The Second Hospital of Shandong University, Yan'an Affiliated Hospital of Kunming Medical University, The Children's Hospital of Zhejiang University School of Medicine, Hunan Children's Hospital, Zhengzhou Children's Hospital, China, Chengdu Women's and Children's Central Hospital, The People's Hospital of Dehong Autonomous Prefecture, Kunming Children's Hospital, Chongqing Three Gorges Central Hospital, Shanxi Provincial Maternity and Children's Hospital, University of Southern California, Vilnius University, Children's Hospital of Fudan University, Guangdong Women and Children Hospital, Nanjing Children's Hospital
- Responsible party
- Sponsor-investigator, Xingwang Zhu, Jiulongpo No.1 People's Hospital
- Investigators
- Shi Yuan, PhD, Study director, Third Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03099694
- Sponsor's protocol ID
- Jiulongpo People's Hospital
- Status last verified
- Feb 2021
- First submitted
- 17 Nov 2016
- Last updated
- 2 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Dr. Kris Sekar, Professor of Pediatrics, Oklahoma University Medical Center, Oklahoma, Dr. Jatinder Bhatia, Professor of Pediatrics, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia, and Dr. Rowena Cayabyab, MD., MPH (Biostatistics and Epidemiology) Assistant Professor of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, California will serve as DSMB members. Dr. Cayabyab will also serve as consultant for statistical analysis.
Publications
Zhu X, Feng Z, Liu C, Shi L, Shi Y, Ramanathan R; NHFOV study group. Nasal High-Frequency Oscillatory Ventilation in Preterm Infants with Moderate Respiratory Distress Syndrome: A Multicenter Randomized Clinical Trial. Neonatology. 2021;118(3):325-331. doi: 10.1159/000515226. Epub 2021 Apr 7.
PubMed 33827081Zhu XW, Shi Y, Shi LP, Liu L, Xue J, Ramanathan R; NHFOV Study Group. Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocol for a multi-center prospective randomized controlled trial. Trials. 2018 Jun 14;19(1):319. doi: 10.1186/s13063-018-2673-9.
PubMed 29898763
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Noninvasive Ventilation for Preterm Neonates With Respiratory Distress Syndrome: a Multi-center Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03099694
- Acronym / sponsor ID
- Jiulongpo People's Hospital
- Conditions
- Preterm Infants
- Keywords
- NRDS, nHFOV, nCPAP, preterm infants
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- Xingwang ZhuUniversity, hospital or other
- Collaborators
- Guiyang Maternity and Child Health Care Hospital, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University, Children's Hospital of Chongqing Medical University, Chongqing Maternal and Child Health Hospital, The Second Hospital of Shandong University, Yan'an Affiliated Hospital of Kunming Medical University, The Children's Hospital of Zhejiang University School of Medicine, Hunan Children's Hospital, Zhengzhou Children's Hospital, China, Chengdu Women's and Children's Central Hospital, The People's Hospital of Dehong Autonomous Prefecture, Kunming Children's Hospital, Chongqing Three Gorges Central Hospital, Shanxi Provincial Maternity and Children's Hospital, University of Southern California, Vilnius University, Children's Hospital of Fudan University, Guangdong Women and Children Hospital, Nanjing Children's Hospital
- Study start
- 27 Apr 2017 (actual)
- Primary completion
- 28 Jul 2018 (actual)
- Study completion
- 28 Jul 2018 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 10 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators compared advantages and disadvantages of two forms of noninvasive respiratory support -noninvasive high-frequency oscillatory ventilation (nHFOV) or nasal continuous positive airway pressure (nCPAP) -as a primary mode of ventilation in premature infants with RDS．
Detailed description
Background: Invasive mechanical ventilation is associated with development of adverse pulmonary and non-pulmonary outcomes in very low birth weight infants. Various modes of non-invasive respiratory support are being increasingly used to minimize the incidence of bronchopulmonary dysplasia (BPD). The aim of this trials to compare the effect of noninvasive high-frequency oscillatory ventilation (NHFOV) and nasal continuous positive airway pressure (NCPAP) in preterm infants with respiratory distress syndrome (RDS) as a primary noninvasive ventilation support mode.
Methods/Design:In this multicenter, randomized, controlled trial, 300 preterm infants at gestational age (GA) less than 34 weeks with a diagnosis of RDS will be randomized to NHFOV or NCPAP as a primary mode of non-invasive respiratory support. Study will be conducted in 18 tertiary neonatal intensive care units in China.
The primary outcome is the need for invasive mechanical ventilation (IMV)during the first 7 days after enrollment in preterm infants randomized to the two groups. The secondary outcomes include days of hospitalization, days on noninvasive respiratory support, days on IMV, days on supplemental oxygen, mortality, need for surfactant, incidence of retinopathy of prematurity(ROP) and bronchopulmonary dysplasia(BPD), occurrence of abdominal distention, air leaks, intraventricular hemorrhage (IVH ≥ grade 3) and necrotizing enterocolitis (NEC> II stage). Other secondary outcomes include scores of Bayley Scales of Infant Development at 2 months and 2 years of corrected age.
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: nasal continuous positive airway pressure (nCPAP)nasal continuous positive airway pressure (nCPAP) - as a primary mode of ventilation in premature infants with RDS |
| nHFOV | Experimental | Procedure: noninvasive high-frequency ventilation (nHFOV)noninvasive high-frequency ventilation (nHFOV) as a primary mode of ventilation in premature infants with RDS |
Who may qualify
- Ages
- Up to 12 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- (1)Gestational age (GA) is from 26 to 34 weeks; (2) diagnosis of RDS. The diagnosis of RDS will be based on clinical manifestations (tachypnea, nasal flaring and or grunting) and chest X-ray findings; (3) RDS Silverman score>5; (4) informed parental consent has been obtained.
Key exclusion criteria (1 listed)
- severe RDS requiring early intubation according to the American Academy of Pediatrics guidelines for neonatal resuscitation7; (2)major congenital malformations or complex congenital heart disease; (3) group B hemolytic streptococcus pneumonia, septicemia, pneumothorax, pulmonary hemorrhage; (4) cardiopulmonary arrest needing prolonged resuscitation; (5) transferred out of the NICUs without treatment.
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 |
|---|---|---|
| noninvasive high-frequency ventilation (nHFOV)NHFOV will be provided by a high frequency ventilator (CNO, Medin, Germany or SLE 5000, UK). NHFOV will be provided via binasal prongs. | Procedure or surgery | nHFOV |
| nasal continuous positive airway pressure (nCPAP)Infants assigned to the NCPAP group will be started on a pressure of 6 cmH2O (range: 6-8 cmH2O) by CPAP system (CNO Medin, Germany, Carefusion, USA) | Procedure or surgery | nCPAP |
Primary outcome
Number of Participants Who Required Intubation
Time frame: during the first 7 days after birth
The criteria for endotracheal mechanical ventilation were as follows: severe respiratory acidosis (PaCO2 > 60 mmHg with pH<7.20), severe apnea and bradycardia (defined as recurrent apnea with > 3 episodes per hour associated with heart rate < 100/min, a single episode of apnea that required bag and mask ventilation), hypoxia (FiO2>0.5 with PaO2<50mmHg), severe respiratory distress, neonatal pulmonary hemorrhage, and cardiopulmonary arrest without effective resuscitation needing continued ventilation and rescue
12 secondary outcomes
the Incidence of Intraventricular Hemorrhage (IVH, ≥ Grade Ⅲ)
Time frame: first two months after birth
the Incidence of Pneumothorax
Time frame: during non-invasive ventilation, up to 7 days
the Incidence of Neonatal Necrotizing Enterocolitis(>Stage II)
Time frame: during non-invasive ventilation, up to 7 days
the Incidence of Retinopathy of Prematurity (>Stage II)
Time frame: at a post-menstrual age of 36 weeks or at discharge
The Score of Bayley Scales of Infant Development
Time frame: 30 months
the Incidence of Bronchopulmonary Dysplasia(BPD)
Time frame: at a post-menstrual age of 36 weeks or at discharge
the Incidence of Abdominal Distention
Time frame: during non-invasive ventilation, up to 7 days
The Time of Non-invasive Ventilation
Time frame: during non-invasive ventilation, up to 30 days
Length of Hospitalization
Time frame: during hospitalization, up to 60 days
Predischarge Mortality
Time frame: during hospitalization, up to 60 days
Length of O2 Therapy
Time frame: during hospitalization, up to 60 days
Number of Participants With Thick Secretions Causing an Airway Obstruction
Time frame: during non-invasive ventilation, up to 15 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33827081Zhu X, Feng Z, Liu C, Shi L, Shi Y, Ramanathan R; NHFOV study group. Nasal High-Frequency Oscillatory Ventilation in Preterm Infants with Moderate Respiratory Distress Syndrome: A Multicenter Randomized Clinical Trial. Neonatology. 2021;118(3):325-331. doi: 10.1159/000515226. Epub 2021 Apr 7.
- Derived from this study: PubMed 29898763Zhu XW, Shi Y, Shi LP, Liu L, Xue J, Ramanathan R; NHFOV Study Group. Non-invasive high-frequency oscillatory ventilation versus nasal continuous positive airway pressure in preterm infants with respiratory distress syndrome: Study protocol for a multi-center prospective randomized controlled trial. Trials. 2018 Jun 14;19(1):319. doi: 10.1186/s13063-018-2673-9.
- Individual participant dataSharing planned: Yes. Dr. Kris Sekar, Professor of Pediatrics, Oklahoma University Medical Center, Oklahoma, Dr. Jatinder Bhatia, Professor of Pediatrics, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia, and Dr. Rowena Cayabyab, MD., MPH (Biostatistics and Epidemiology) Assistant Professor of Pediatrics, Keck School of Medicine of the University of Southern California, Los Angeles, California will serve as DSMB members. Dr. Cayabyab will also serve as consultant for statistical analysis.
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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.
Shi Yuan, PhD study director
Third Military Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing noninvasive high-frequency ventilation (nHFOV) and nasal continuous positive airway pressure (nCPAP) in people with Preterm Infants, run by Xingwang Zhu 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 1 inclusion and 1 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 2 Mar 2021. 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?
Yes. Results are posted in the registry (first posted 10 Jun 2019). 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?
Number of Participants Who Required Intubation (time frame: during the first 7 days after birth). 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 NCT03099694, 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 2 Mar 2021.