Noninvasive High Frequency Oscillatory Ventilation Versus Nasal Intermittent Mandatory Ventilation for Respiratory Distress Syndrome in Preterm Neonates

NCT07837141 | Not Yet Recruiting DMC

• 1 other identifier: 13551
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if nasal high frequency oscillatory ventilation (nHFOV) works no worse than nasal intermittent mandatory ventilation (NIMV) as early breathing support. The study will include preterm babies born from 28 weeks through 36 weeks of gestation..All babies will have respiratory distress syndrome and need noninvasive breathing support within six hours of birth. Noninvasive support helps breathing through a nasal interface without placing a tube in the windpipe. The main questions it aims to answer are: Does nHFOV work no worse than NIMV in preventing the need for a breathing tube within 72 hours? What medical problems occur in babies receiving each type of breathing support? Researchers will compare nHFOV with NIMV. nHFOV uses rapid, small pressure waves. NIMV provides regular supported breaths. Both methods are routinely used at the study hospital. Babies will: Be assigned by chance to receive either nHFOV or NIMV Receive regular monitoring of breathing, oxygen levels, and medical condition Be assessed for the need for a breathing tube during the first 72 hours Be followed for complications of disease and assigned treatment during hospitalization and after discharge when required The study will also record breathing support duration, hospital stay, survival, chronic lung disease, severe bleeding in the brain, and eye disease related to prematurity. The findings may help doctors choose breathing support for preterm babies with respiratory distress syndrome.

Conditions

Newborn; Premature Birth; Respiratory Distress Syndrome (RDS)

Keywords

Preterm Neonates; Neonatal Respiratory Distress Syndrome; Noninvasive High-Frequency Oscillatory Ventilation; Nasal Intermittent Mandatory Ventilation; Primary Respiratory Support; Noninvasive Respiratory Support; Treatment Failure; Invasive Mechanical Ventilation

Outcome Measures

Primary Outcomes (1)

• Proportion of preterm neonates with treatment failure requiring invasive mechanical ventilation

  Treatment failure is defined as initiation of invasive mechanical ventilation due to any of the following: pH \<7.20 with pCO₂ \>60 mmHg on two blood gas measurements at least 30 minutes apart, SpO₂ \<90% with FiO₂ \>0.60 for at least 15 minutes on maximal noninvasive support; at least one apnea episode requiring bag mask ventilation; Silverman Anderson Score ≥7 on maximal noninvasive support; hemodynamic instability requiring inotropic support secondary to respiratory failure, or the physician's decision to intubate for clinical reasons with written justification. The number and proportion of neonates meeting the treatment failure criteria will be reported in each study arm.

  Within 72 hours after randomization

Secondary Outcomes (3)

• Proportion of Eligible Neonates With Bronchopulmonary Dysplasia at 36 Weeks' Postmenstrual Age Description

  At 36 weeks' postmenstrual age

• Proportion of eligible neonates with severe intraventricular hemorrhage

  From randomization until 44 weeks' postmenstrual age or final hospital disposition, whichever occurs first

• Proportion of Eligible Neonates With Treatment-Requiring Retinopathy of Prematurity

  From the first ROP screening examination until 44 weeks' postmenstrual age or discharge from ROP screening by the treating ophthalmologist, whichever occurs first

Other Outcomes (10)

• Duration of noninvasive respiratory support

  From randomization until final hospital disposition, or 44 weeks' postmenstrual age, whichever occurs first;

• Duration of invasive mechanical ventilation

  From the first initiation of invasive mechanical ventilation after randomization until final hospital disposition, or 44 weeks' postmenstrual age, whichever occurs first;

• Duration of supplemental oxygen therapy

  From randomization until final discontinuation of supplemental oxygen or 44 weeks' postmenstrual age, whichever occurs first

Study Arms (2)

Nasal High-Frequency Oscillatory Ventilation (nHFOV)

EXPERIMENTAL

Preterm neonates randomized to this arm will receive nasal high frequency oscillatory ventilation (nHFOV) as primary respiratory support through a RAM cannula or Infant Flow Generator. Initial settings will include mean airway pressure of 10-12 cmH₂O, amplitude of 15-25 cmH₂O, frequency of 8-12 Hz, and an inspiratory to expiratory ratio of 1:1. Settings will be adjusted according to clinical response to maintain SpO₂ between 90% and 95%.

Device: Noninvasive High Frequency Oscillatory Ventilation

Nasal Intermittent Mandatory Ventilation (NIMV)

ACTIVE COMPARATOR

Preterm neonates randomized to this arm will receive nasal intermittent mandatory ventilation (NIMV) as primary respiratory support through a RAM cannula or Infant Flow Generator. Initial settings will include PEEP of 8-12 cmH₂O, peak inspiratory pressure of 18-24 cmH₂O, inspiratory time of 0.5 seconds, and respiratory rate of 30 breaths per minute. Settings, including FiO₂, will be adjusted according to clinical response to maintain SpO₂ between 90% and 95%.

Device: Nasal Intermittent Mandatory Ventilation

Interventions

Nasal Intermittent Mandatory Ventilation DEVICE

Nasal intermittent mandatory ventilation will be delivered as primary respiratory support through a nasal interface using a RAM cannula or Infant Flow Generator and an NIMV capable ventilator. Initial settings will include PEEP of 8-12 cmH₂O, peak inspiratory pressure of 18-24 cmH₂O, inspiratory time of 0.5 seconds, and respiratory rate of 30 breaths per minute. The respiratory rate may be increased by 5 breaths per minute to a maximum of 50 breaths per minute based on PaCO₂. FiO₂ and other ventilator settings may be adjusted according to clinical response to maintain SpO₂ between 90% and 95%.

Also known as: NIMV, Nasal Intermittent Positive Pressure Ventilation, NIPPV

Nasal Intermittent Mandatory Ventilation (NIMV)

Noninvasive High Frequency Oscillatory Ventilation DEVICE

Noninvasive high frequency oscillatory ventilation will be delivered as primary respiratory support through a nasal interface using a RAM cannula or Infant Flow Generator and an nHFOV capable ventilator. Initial settings will include mean airway pressure of 10-12 cmH₂O, amplitude of 15-25 cmH₂O, frequency of 8-12 Hz, and an inspiratory to expiratory ratio of 1:1. Mean airway pressure may be increased by 1 cmH₂O to a maximum of 20 cmH₂O, and amplitude may be increased by 5 cmH₂O to a maximum of 35 cmH₂O. Settings will be adjusted according to clinical response to maintain SpO₂ between 90% and 95%.

Also known as: nHFOV, Nasal High Frequency Oscillatory Ventilation

Nasal High-Frequency Oscillatory Ventilation (nHFOV)

Eligibility Criteria

• Age: 0 Hours - 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm neonates born between 28+0 and 36+0 weeks of gestation, whether inborn or outborn
• Gestational age confirmed by first-trimester ultrasound, last menstrual period, or Ballard score
• Clinical and radiological evidence of respiratory distress syndrome
• Requirement for NIMV-level noninvasive respiratory support according to the protocol-defined criteria
• Enrollment and randomization within 6 hours after birth
• Written informed consent provided by a parent or legal guardian

You may not qualify if:

• Intubation and receipt of invasive mechanical ventilation at the time of enrollment
• Receipt of surfactant before randomization by any method, including INSURE, LISA, MIST, or surfactant administration before transfer to Aga Khan University Hospital
• Major congenital anomaly affecting respiratory or cardiovascular physiology

Sponsors & Collaborators

• Aga Khan University: lead

Study Sites (1)

Aga Khan University Hospital, Karachi Stadium Road, P.O.Box 3500 Karachi 74800, Pakistan

Karachi, Sindh, 74800, Pakistan

Location

Related Publications (4)

• Ali R, Mahmud S. Nasal high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation in pre-terms with respiratory distress syndrome during the early neonatal period: a randomized controlled trial. Pakistan Armed Forces Medical Journal. 2023;73(1):151-154. doi:10.51253/pafmj.v73i1.8186.

  BACKGROUND

• Likhitha P, Ramaswamy VV, Shaik NB, Basany L, Ali AAH. Non-invasive high-frequency oscillation ventilation versus nasal CPAP as primary respiratory support in preterm neonates >/= 30 weeks with RDS: a non-inferiority randomized controlled trial. Eur J Pediatr. 2026 Mar 25;185(4):210. doi: 10.1007/s00431-026-06887-6.

  PMID: 41876901 BACKGROUND

• 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.

  PMID: 33827081 BACKGROUND

• Rachana RD, Oleti T, Saikiran D, Vardhelli V, Thiruveedi S, Hussain A, Tamatam PR. Non-invasive high-frequency oscillatory ventilation versus non-invasive intermittent mandatory ventilation as a rescue mode in preterm infants with respiratory distress on nasal CPAP-a randomized control trial. Eur J Pediatr. 2025 Feb 22;184(3):205. doi: 10.1007/s00431-025-06041-8.

  PMID: 39985666 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome; Premature Birth; Respiratory Distress Syndrome, Newborn

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ali S Hussain, FCPS (Paeds),FCPS Neonatology

  Aga Khan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hafsah Naz, Fellow Paediatric Neonatology

CONTACT

+92 3310478376; hafsah.naz@aku.edu

Ali S Hussain, FCPS (Paeds),FCPS Neonatology

CONTACT

+92 300 2424206; ali.hussain@aku.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The statistical analysis will be performed using treatment groups coded as Group A and Group B. The statistician will remain masked to the identity of the assigned interventions until the primary analysis is completed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Paediatrics

Model Details: Participants will be assigned in a 1:1 ratio to two parallel groups receiving either nHFOV or NIMV. Stratified permuted-block randomization will be used according to gestational age: 28+0 to 31+6 weeks and 32+0 to 36+0 weeks.

Study Record Dates

• First Submitted: September 5, 2026
• First Posted: September 23, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 23, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)