NHFOV as Primary Support in Very Preterm Infants With RDS

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.

Study Overview

• Status: Completed
• Conditions: to Test the Hypothesis That NHFOV is More Effective Than nCPAP in the Treatment of Respiratory Distress Syndrome (RDS) in Verypreterm Neonates
• Intervention / Treatment: Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP; Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV

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 Type: Interventional
• Enrollment (Actual): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Hunan Provincial Maternal and Child Health Care Hospital
  • Shandong
    • Jinan, Shandong, China
      • The Second Hospital of Shandong University
  • Yunnan
    • Qujing, Yunnan, China
      • Qujing Maternity and cChild Healthcare Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 hours (Child)
• Accepts Healthy Volunteers: No

Description

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

Exclusion Criteria:

• Intubated forany reasons at birth

  • Major congenital malformations or known complex congenital heart disease
  • No parental consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NCPAP	Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP; 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.; Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV; 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).
Active Comparator: NHFOV	Procedure: infants receive primary non-invasive respiratory support by mean of nCPAP; 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.; Procedure: infants receive primary non-invasive respiratory support by mean of NHFOV; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	within 72 hrs from the beginning of the study mode

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Airleaks(Pneumothorax and/or Pneumomediastinum) Occurred During Noninvasive Respiratory Support	the diagnosis a Chest XR	the first 4weeks of life or until NICU discharge, whichever comes first

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Bronchopulmonary Dysplasia	defined according to the NICHD definition	36 weeks of postmenstrual age
Rate of Retinopathy of Prematurity (ROP)≥ 2nd Stage		the first 4weeks of life or until NICU discharge, whichever comes first
Rate of Necrotizing Enterocolitis (NEC) ≥ 2nd Stage		the first 4weeks of life or until NICU discharge, whichever comes first
Rate of Intraventricular Hemorrhage ≥ 3nd Grade		the first 4weeks of life or until NICU discharge, whichever comes first
Rate of Thick Secretions Causing an Airway Obstruction		the first 4weeks of life or until NICU discharge, whichever comes first
In-hospital Mortality		through study completion, an average of 1 year
Rate of Nasal Trauma		the first 4weeks of life or until NICU discharge, whichever comes first
Composite Mortality/BPD Tality/BPD		through study completion, an average of 1 year
Weekly Weight Gain	in grams/d	the first 4weeks of life or until NICU discharge, whichever comes first
Overall Duration of Non Invasive Respiratory Assistance		the first 4weeks of life or until NICU discharge, whichever comes first
Overall Duration of Hospitalisation		up to 2 years from birth
the Rate of Patent Doctus Arterious	If a pharmaceutical or surgical treatment is required is considered. Small doctuses closing spontaneously during the first days of life are not included.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Jiulongpo No.1 People's Hospital
• Collaborators: People's Hospital of Xinjiang Uygur Autonomous Region; The Second Hospital of Shandong University; Chengdu Women's and Children's Central Hospital; Xiamen Maternity & Child Care Hospital; Quanzhou Children's Hospital; Children's Hospital of Chongqing Medical University; The First People's Hospital of Yunnan; International Peace Maternity and Child Health Hospital; Liuzhou Maternity and Child Healthcare Hospital; Hunan Provincial Maternal and Child Health Care Hospital; Jiangxi Maternal and Child Health Hospital; Chongqing Medical Center for Women and Children; Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region; Chongqing Three Gorges Central Hospital; Women and Children's Health Hospital of Yulin; Maternal and Children's Healthcare Hospital of Taian; Guiyang Maternity and Child Health Care Hospital; Zhangzhou Affiliated Hospital of Fujian Medical University; Gansu Provincial Maternal and Child Health Care Hospital; Chongqing West Hospital; Qujing Maternal and Child Health Hospital
• Investigators: Study Chair: Yuan Shi, PhD, Children's Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): August 5, 2024
• Study Completion (Actual): August 5, 2024

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: November 19, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): July 24, 2025
• Last Update Submitted That Met QC Criteria: July 13, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: nasal high frequency oscillation ventilation(NHFOV); nasal continuous positive airway pressure(NCPAP); preterm infants
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: NHFOV prevent intubation

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No