High-Frequency Oscillation Ventilation Versus Conventional Mechanical Ventilation in Very Preterm Infants With Perinatal Acute Respiratory Distress Syndrome: Multicenters Randomized Controlled, Superiority Trial

Not Applicable

Recruiting

• Conditions: Acute Respiratory Distress Syndrome; High Frequency Oscillatory Ventilation; Preterm; Conventional Mechanical Ventilation

• Registration Number: NCT03736707
• Lead Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

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.

Detailed Description

Before 2017, the management guideline of pediatric and adult acute respiratory distress syndrome (ARDS) exclude perinatal triggers-induced ARDS. Moreover, there is insufficient evidence to recommend high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) as the preferred fist-line therapy in pediatric and adult ARDS. In contrast, HFOV may benefit preterm baboons with acute pulmonary dysfunction-typically due to respiratory distress syndrome (RDS)-by using low tidal volume, supra-physiologically higher respiratory rate, and lower peak inspiratory pressure to enhance oxygenation and gas exchange. The team also reported that use of HFOV is associated with a modest reduction referring to BPD. However, European consensus guideline of RDS only recommend HFOV being a reasonable alternative to CMV when high pressure is needed to achieve adequate lung inflation. Because randomized controlled trials in humans have yielded inconsistent findings.

These differences between animal models-where RDS was induced and treated with surfactant alone-and clinical scenarios, where preterm birth often involved complex etiologies requiring both surfactant and antibiotics for placental insufficiency or intrauterine infection, may be the diagnosis of RDS and ARDS or the mixture of RDS and ARDS. Such findings highlighted the lack of robust evidence for optimizing ventilation strategies in preterm infants born \<32 weeks with perinatal ARDS, and the need for well-designed multi-center randomized controlled trials in this high-risk population.

Study Timeline

• Study First Submitted: 2018-11-07
• Study First Submitted QC: 2018-11-07
• Study First Posted: 2018-11-09
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-30
• Study Start: 2025-10-01
• Last Update Posted: 2025-10-06
• Primary Completion: 2028-06-30
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
the incidence of bronchopulmonary dysplasia(BPD)	36 weeks' gestational age	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.

Secondary Outcome Measures

Name	Time	Method
duration of invasive ventilation	36 weeks' gestational age	duration of invasive ventilation for HFOV or CMV
mortality	36 weeks' gestational age or before discharge	the included neonates were diagnosed with death
air leak (pneumothorax and/or pneumomediastinum) occurred	36 weeks' gestational age or before discharge	the included neonates were diagnosed with air leak
the incidence of hemodynamically significant patent ductus arteriosus (hsPDA)	36 weeks' gestational age or before discharge	the included neonates were diagnosed with hsPDA.
the incidence of retinopathy of prematurity(ROP)> 2nd grades	36 weeks' gestational age or before discharge	ROP was categorized according to the International Classification of Retinopathy of Prematurity, revised in 2005
the incidence of necrotizing enterocolitis(NEC)≥2nd stages	36 weeks' gestational age or before discharge	the development of NEC, specifically focusing on cases classified as Bell's stage ≥2, according to the modified Bell's staging criteria for NEC.
intraventricular hemorrhage(IVH)>2nd grade	36 weeks' gestational age or before discharge	IVH with grades 1-4 were defined by Papile et al

Trial Locations

Locations (1)

Children's Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing Municipality, China