An interventional study of Noninvasive High Frequency Oscillatory Ventilation and Nasal Intermittent Mandatory Ventilation in Respiratory Distress Syndrome (RDS), Newborn and Premature Birth, sponsored by Aga Khan University. Not yet recruiting at 1 site in Pakistan. Open to participants aged 0 Hours to 6 Hours. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by Aga Khan University · Not applicable, Interventional, and Treatment
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.
Direct comparisons of nasal high frequency oscillatory ventilation (nHFOV) and nasal intermittent mandatory ventilation (NIMV) as primary respiratory support for preterm neonates with respiratory distress syndrome are limited, particularly in Pakistan and other lower middle income settings. Both methods are routinely used at Aga Khan University Hospital, but the choice between them currently depends mainly on the treating clinician's preference. This study is intended to provide local evidence that may guide a more standardized approach to early noninvasive respiratory support.
This is a prospective, single center, open label, parallel group, non inferiority randomized controlled trial. A total of 158 neonates will be assigned in a 1:1 ratio using stratified permuted block randomization based on gestational age. Allocation will be concealed using sequentially numbered, opaque, sealed envelopes prepared by an independent biostatistician. Because the two ventilation modes use visibly different settings, treating clinicians and research personnel will not be blinded. Statistical analysis will remain blinded until completion of the primary analysis.
The primary analysis will estimate the risk difference in treatment failure between the nHFOV and NIMV groups with a two-sided 95% confidence interval. nHFOV will be considered non-inferior if the upper limit of the confidence interval is below the prespecified absolute non-inferiority margin of 15 percentage points. Both intention to treat and per protocol analyses will be performed. An independent Data and Safety Monitoring Board will review safety data after approximately 25%, 50%, and 75% of planned enrollment.
123 studies on the registry are indexed under Respiratory Distress Syndrome, Newborn; 24 are open to participants now.
This study's planned enrollment of 158 is above the median of 90 across 93 interventional studies indexed under Respiratory Distress Syndrome, Newborn.
Browse Respiratory Distress Syndrome, Newborn studies →Aga Khan University is the lead sponsor of 294 studies on the registry; 43 are open to participants now.
Compared within Respiratory Distress Syndrome, Newborn, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Respiratory Distress Syndrome. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
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 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
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.
Time frame: Within 72 hours after randomization
Proportion of Eligible Neonates With Bronchopulmonary Dysplasia at 36 Weeks' Postmenstrual Age Description
Among enrolled neonates born at ≤32 weeks' gestation who survive to 36 weeks' PMA, BPD will be classified according to respiratory support at 36 weeks using Jensen et al. (2019): no BPD, no respiratory support; Grade 1, nasal cannula ≤2 L/min; Grade 2, nasal cannula \>2 L/min or noninvasive positive-pressure support; and Grade 3, invasive mechanical ventilation. Respiratory status will be obtained from inpatient records, outpatient assessment, or telephone follow-up. Neonates who die before 36 weeks' PMA will be excluded from BPD ascertainment.
Time frame: At 36 weeks' postmenstrual age
Proportion of eligible neonates with severe intraventricular hemorrhage
The proportion of enrolled neonates born at \<32 weeks' gestation or with a birth weight \<1,500 g who develop severe IVH will be reported for each study arm. Severe IVH is defined according to the Papile classification as Grade III, IVH occupying ≥50% of the ventricular area with ventricular dilatation, or Grade IV, IVH with periventricular echodensity consistent with periventricular hemorrhagic infarction. All routine and clinically indicated cranial ultrasounds obtained during the assessment period will be included and reported by a consultant radiologist blinded to treatment allocation.
Time frame: From randomization until 44 weeks' postmenstrual age or final hospital disposition, whichever occurs first
Proportion of Eligible Neonates With Treatment-Requiring Retinopathy of Prematurity
The proportion of enrolled neonates born at \<32 weeks' gestation or with a birth weight \<1,500 g who develop treatment-requiring ROP in either eye will be reported for each study arm. Screening will be performed by a consultant ophthalmologist, and ROP will be classified according to ICROP3. Treatment-requiring ROP is defined as Type 1 ROP-Zone I ROP of any stage with plus disease, Zone I Stage 3 without plus disease, or Zone II Stage 2 or 3 with plus disease-aggressive ROP, or Stage 4 or 5 ROP. Treatment may include laser photocoagulation, intravitreal anti-VEGF therapy, or vitreoretinal surgery. Findings will be obtained from inpatient records and scheduled post-discharge ophthalmology follow-up.
Time frame: From the first ROP screening examination until 44 weeks' postmenstrual age or discharge from ROP screening by the treating ophthalmologist, whichever occurs first
Duration of noninvasive respiratory support
The cumulative duration for which each participant receives noninvasive respiratory support after randomization will be recorded and reported in days, including the assigned nHFOV or NIMV intervention and any subsequent noninvasive positive pressure respiratory support. Heated humidified high flow nasal cannula and supplemental oxygen alone will not be included. The duration will be compared between the two study arms.
Time frame: From randomization until final hospital disposition, or 44 weeks' postmenstrual age, whichever occurs first;
Duration of invasive mechanical ventilation
Among participants who require intubation and invasive mechanical ventilation after randomization, the cumulative duration of all invasive mechanical ventilation episodes will be recorded and reported in days. The duration will be compared between the nHFOV and NIMV study arms.
Time frame: 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
The cumulative duration for which each participant receives supplemental oxygen after randomization will be recorded and reported in days. This will include supplemental oxygen delivered through invasive mechanical ventilation, noninvasive respiratory support, heated humidified high-flow nasal cannula, low-flow nasal cannula, oxygen hood, or any other oxygen delivery device. The duration will be compared between the nHFOV and NIMV study arms.
Time frame: From randomization until final discontinuation of supplemental oxygen or 44 weeks' postmenstrual age, whichever occurs first
Proportion of neonates receiving surfactant after randomization
The number and proportion of neonates who receive at least one dose of surfactant after randomization will be recorded and compared between the nHFOV and NIMV study arms.
Time frame: From randomization until final hospital disposition or 44 weeks' postmenstrual age, whichever occurs first
Proportion of neonates developing an air leak syndrome while receiving assigned respiratory support
The number and proportion of participants who develop a radiographically confirmed air leak syndrome including pneumothorax, pulmonary interstitial emphysema, or pneumomediastinum while receiving their assigned nHFOV or NIMV respiratory support will be recorded and compared between the study arms. Air leaks occurring after discontinuation of the assigned modality will not be included in this outcome.
Time frame: From initiation of the assigned respiratory support until its discontinuation or 7 days after randomization, whichever occurs first
Proportion of neonates developing Stage II or higher necrotizing enterocolitis
The number and proportion of participants who develop Stage II or higher necrotizing enterocolitis according to the modified Bell criteria will be recorded and compared between the nHFOV and NIMV study arms. Suspected Stage I necrotizing enterocolitis will not be included in this outcome.
Time frame: From randomization until final hospital disposition or 44 weeks' postmenstrual age, whichever occurs first
Proportion of neonates with hemodynamically significant patent ductus arteriosus requiring treatment
The number and proportion of participants diagnosed with a hemodynamically significant patent ductus arteriosus requiring medical treatment or surgical ligation, based on clinical and echocardiographic findings, will be recorded and compared between the nHFOV and NIMV study arms.
Time frame: From randomization until final hospital disposition or 44 weeks' postmenstrual age, whichever occurs first
Nasal injury during noninvasive respiratory support
Nasal injury attributable to the assigned noninvasive respiratory interface will be assessed at least every 24 hours using the modified Fischer classification: Grade 0, no injury; Grade 1, erythema or discoloration without skin breakdown; Grade 2, superficial erosion or ulceration; and Grade 3, full-thickness tissue loss, necrosis, or cartilage damage. The highest grade recorded for each participant during the assessment period will be compared between the study arms.
Time frame: From randomization until discontinuation of the assigned noninvasive respiratory support or 7 days after randomization, whichever occurs first
Duration of hospital stay
The duration of hospitalization will be calculated in days from hospital admission until final hospital disposition, defined as discharge, transfer, leaving against medical advice, or death. The duration will be compared between the nHFOV and NIMV study arms.
Time frame: From hospital admission until final hospital disposition or 44 weeks' postmenstrual age, whichever occurs first
Proportion of neonates with all cause in hospital mortality
The number and proportion of participants who die from any cause during hospitalization after randomization will be recorded and compared between the nHFOV and NIMV study arms. Final hospital disposition is defined as discharge, transfer to another unit or facility, leaving against medical advice, or death.
Time frame: From randomization until final hospital disposition or 44 weeks' postmenstrual age, whichever occurs first
Plan to share: No — Individual participant data will not be shared because the study involves a vulnerable neonatal population, and no external IPD sharing repository or formal data sharing framework has been established. Study findings will be reported in aggregate form through trial registration, scientific presentations, and peer-reviewed publication, without disclosing participant identities.
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Respiratory Distress Syndrome, Newborn →