NCT03736707

Brief Summary

Bronchopulmonary dysplasia (BPD) is a complex disorder and remains the most common complication in very preterm infants. Its incidence is increased with gestational age from 95.5% among infants born at 22 weeks' gestation to 22.2% among those born at 29 weeks' gestation. BPD is associated with the increased risks of delayed neurodevelopment and pulmonary impairment. High incidences of BPD and morbidities indicate inadequacy of current management guidelines of BPD.3 Caffeine reduces the development of BPD by lowering the duration of intubation.4 How to further reduce the risk of BPD and the duration of invasive ventilation remain the key focus for neonatologists.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P75+ for not_applicable

Timeline
33mo left

Started Oct 2025

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress17%
Oct 2025Dec 2028

First Submitted

Initial submission to the registry

November 7, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 9, 2018

Completed
6.9 years until next milestone

Study Start

First participant enrolled

October 1, 2025

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

October 6, 2025

Status Verified

September 1, 2025

Enrollment Period

2.7 years

First QC Date

November 7, 2018

Last Update Submit

September 30, 2025

Conditions

Acute Respiratory Distress SyndromeHigh Frequency Oscillatory VentilationPretermConventional Mechanical Ventilation

Outcome Measures

Primary Outcomes (1)

  • the incidence of bronchopulmonary dysplasia(BPD)

    BPD is defined according to the 2019 diagnostic criteria. For infants discharged before 36 weeks' GA, BPD severity was assessed based on respiratory support at the time of discharge. Infants receiving no supplemental respiratory support were divided into no BPD, those treated with nasal cannula (≤ 2 L/min) as grade 1 BPD, those treated with nasal cannula (\> 2 L/min) or noninvasive positive airway pressure as grade 2 BPD and those treated with invasive mechanical ventilation as grade 3 BPD.

    36 weeks' gestational age

Secondary Outcomes (7)

  • duration of invasive ventilation

    36 weeks' gestational age

  • mortality

    36 weeks' gestational age or before discharge

  • air leak (pneumothorax and/or pneumomediastinum) occurred

    36 weeks' gestational age or before discharge

  • the incidence of hemodynamically significant patent ductus arteriosus (hsPDA)

    36 weeks' gestational age or before discharge

  • the incidence of retinopathy of prematurity(ROP)> 2nd grades

    36 weeks' gestational age or before discharge

  • +2 more secondary outcomes

Study Arms (2)

high frenquency oscillation ventilation (HFOV)

EXPERIMENTAL

HFOV + volume guarantee (VG) as the intervention group HFOV was provided only with piston or membrane oscillators capable of delivering true oscillatory pressure with an active expiratory phase (i.e., Acutronic FABIAN-III, SLE 5000, Löwenstein Med LEONI+, or Sensormedics 3100A). Other machines offering high frequency ventilation were excluded. The lung recruitment maneuver was performed as previously described,15 and lung volume was assessed by chest radiography or lung ultrasound, targeting the right diaphragm at the level of 8th-9th rib (or 7th-8th rib in case of air leak). Crossover between HFOV and CMV This study allowed infants who failed to respond to their assigned ventilation mode to receive a trial of the alternate mode. Crossover criteria for HFOV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or signs of ventilator-induced cardiac output reduction. Non-responders to HFOV were switched to CMV.

Device: HFOV

conventional mechanical ventilation (CMV)

ACTIVE COMPARATOR

CMV was delivered by time-cycled, pressure-limited ventilators. Only pressure regulated volume control (PRVC) will be provided by any type of neonatal ventilator. Crossover criteria for CMV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or requiring \> 30 cm H2O PIP to sustain ventilation. Non-responders to CMV were switched to HFOV. in both groups, ventilator settings were adjusted at the discretion of the attending clinician to maintain a SpO2 between 90%-94%, a PaO2 between 50 and 80 mm Hg and a PaCO2 between 35 and 60 mm Hg and a pH between 7.20 and 7.45. PO2 and PCO2 levels were monitored using arterial blood gas analysis and/or transcutaneous monitoring.

Device: CMV

Interventions

HFOVDEVICE

HFOV + volume guarantee (VG) as the intervention group HFOV was provided only with piston or membrane oscillators capable of delivering true oscillatory pressure with an active expiratory phase (i.e., Acutronic FABIAN-III, SLE 5000, Löwenstein Med LEONI+, or Sensormedics 3100A). Other machines offering high frequency ventilation were excluded. The lung recruitment maneuver was performed as previously described, and lung volume was assessed by chest radiography or lung ultrasound, targeting the right diaphragm at the level of 8th-9th rib (or 7th-8th rib in case of air leak). Crossover between HFOV and CMV This study allowed infants who failed to respond to their assigned ventilation mode to receive a trial of the alternate mode. Crossover criteria for HFOV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or signs of ventilator-induced cardiac output reduction. Non-responders to HFOV were switched to CMV.

high frenquency oscillation ventilation (HFOV)
CMVDEVICE

CMV as the standard group CMV was delivered by time-cycled, pressure-limited ventilators. Only pressure regulated volume control (PRVC) will be provided by any type of neonatal ventilator. Crossover criteria for CMV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or requiring \> 30 cm H2O PIP to sustain ventilation. Non-responders to CMV were switched to HFOV. Ventilator settings were adjusted at the discretion of the attending clinician to maintain a SpO2 between 90%-94%, a PaO2 between 50 and 80 mm Hg and a PaCO2 between 35 and 60 mm Hg and a pH between 7.20 and 7.45. PO2 and PCO2 levels were monitored using arterial blood gas analysis and/or transcutaneous monitoring in both groups.

conventional mechanical ventilation (CMV)

Eligibility Criteria

Age1 Minute - 1 Hour
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • GA was between 24+0 and 31+6 weeks.
  • Preterm neonates were admitted to NICU within 1 hours after birth, diagnosed with perinatal ARDS using Montreux guidelines and stable supported by CMV.
  • Stabilization for 2 hours before randomization: FiO2 0.40, mean airway pressure (MAP) 10-14 cmH2O, ≤ 40 bpm of respiratory rate, 90%-94% of SpO2, pH \> 7.20, PaCO2 60 mmHg, tidal volume of 5 ml/kg and \> 35% of hematocrit (these may be evaluated by arterial blood gas analysis).

You may not qualify if:

  • Neonates were not included if any of the following criteria were met:
  • Parents or guardians' decision not to participate.
  • Major congenital anomalies or chromosomal abnormalities
  • Need for surgery or more than grade 2nd of IVH before randomization.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400042, China

RECRUITING

MeSH Terms

Conditions

Respiratory Distress SyndromePremature Birth

Condition Hierarchy (Ancestors)

Lung DiseasesRespiratory Tract DiseasesRespiration DisordersObstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
The caregivers will not be blinded, and the outcome assessors and data analysts will be blinded to the intervention.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Very preterm neonates with perinatal acute respiratory distress syndrome will be randomized and assigned to high frequency oscillation ventilation (HFOV) or conventional mechanical ventilation (CMV)
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 7, 2018

First Posted

November 9, 2018

Study Start

October 1, 2025

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

December 31, 2028

Last Updated

October 6, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)