Combined Oscillation-Volume guarantEe Study

Combined Volume Guarantee High-Frequency Oscillatory Ventilation (HFOV-VG) Versus Conventional High-Frequency Oscillatory Ventilation (HFOV) on Grade 2 to 3 Bronchopulmonary Dysplasia (BPD) or Death in Preterm Infants <32 Weeks With Respiratory Distress Syndrome (RDS)

Respiratory Distress Syndrome (RDS) remains the most common respiratory complication in the early postnatal period among preterm infants born before 32 weeks' gestational age. For this population, implementing lung-protective ventilation strategies is essential to shorten the duration of intubation, reduce the incidence and severity of bronchopulmonary dysplasia (BPD), lower mortality, and improve overall outcomes.

HFOV-VG was first reported in 2015 to be safely applied in neonates. The fundamental principle lies in its ability to stabilize the tidal volume of high-frequency ventilation (VThf), thereby reducing sheer stress from amplitude fluctuations, while simultaneously permitting lower VThf settings to minimize volutrauma.

This study aims to evaluate whether HFOV+VG is superior to HFOV in reducing the composite outcome of grade 2-3 BPD or death at 36 weeks' post-menstrual age (PMA).

Study Overview

• Status: Not yet recruiting
• Conditions: Bronchopulmonary Dysplasia (BPD); Respiratory Distress Syndrome (& [Hyaline Membrane Disease])
• Intervention / Treatment: Device: HFOV; Device: HFOV+VG

• Study Type: Interventional
• Enrollment (Estimated): 348
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuan Shi, PhD; Phone Number: +86 23 68757731; Email: shiyuan@hospital.cqmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Gestational age 24+0/7< 320/7 weeks
• Diagnosis of RDS within 72 hours after birth, requiring endotracheal ventilation for both elective and rescue HFOV

Exclusion Criteria:

• Severe birth defects: severe congenital heart disease, diaphragmatic hernia, gastrointestinal malformations, congenital brain developmental abnormalities, congenital pulmonary cysts
• Uncorrected shock
• Existence of grade 3-4 IVH before ventilated
• Other conditions deemed unsuitable for enrollment by neonatologists, including endotracheal intubation performed specifically for the purpose of the INSURE or INRECSURE technique.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HFOV; HFOV: 1) Mean airway pressure (MAP) and FiO2: titrated via oxygenation-guided lung recruitment maneuvers21-23 to maintain preductal SpO2 target of 89%-94%. 2) Frequency: 12-15 Hz for birth weight (BW)<1500g, and 10-12 Hz for BW≥ 1500g. 3) I:E ratio: 1:1 or 1:2 according to recommendations of manufacturers and local habits	Device: HFOV; HFOV: 1) Mean airway pressure (MAP) and FiO2: titrated via oxygenation-guided lung recruitment maneuvers to maintain preductal SpO2 target of 89%-94%. 2) Frequency: 12-15 Hz for birth weight (BW)<1500g, and 10-12 Hz for BW≥ 1500g. 3) I:E ratio: 1:1 or 1:2 according to recommendations of manufacturers and local habits
Active Comparator: HFOV+VG; HFOV-VG Group: ①VThf: <1000g 1.5-1.8ml/kg, 1000-1500g 1.8-2.2ml/kg, >1500g, 2.2-2.5ml/kg; ②Amplitude automatically adjusted by volume guarantee algorithm and the upper limit was set at 15% above the measured value after achieving the target VThf, with the constraint that it must not exceed 20 cm H2O for BW<1000g, 25cm H2O for BW 1000-1500g or 25-30 cmH2O for BW>1500g; ③If the target VThf is not achieved after the amplitude has reached its upper limit, airway issues (e.g., suctioning) or lung recruitment should be addressed first, rather than overriding the amplitude limit.	Device: HFOV+VG; HFOV-VG Group: ①VThf: <1000g 1.5-1.8ml/kg, 1000-1500g 1.8-2.2ml/kg, >1500g, 2.2-2.5ml/kg; ②Amplitude automatically adjusted by volume guarantee algorithm and the upper limit was set at 15% above the measured value after achieving the target VThf, with the constraint that it must not exceed 20 cm H2O for BW<1000g, 25cm H2O for BW 1000-1500g or 25-30 cmH2O for BW>1500g; ③If the target VThf is not achieved after the amplitude has reached its upper limit, airway issues (e.g., suctioning) or lung recruitment should be addressed first, rather than overriding the amplitude limit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite outcome of grade 2-3 BPD or in-hospital death at 36 weeks' PMA	36 weeks gestational age

Secondary Outcome Measures

Outcome Measure	Time Frame
In-hospital death at 36 weeks' PMA	36 weeks gestational age
The incidence of BPD at 36 weeks' PMA	36 weeks gestational age
The duration of invasive ventilation at the time of the first successful extubation	through study completion, an average of 1 year
Surfactant doses	through study completion, an average of 1 year
The incidence of normocapnia, hypercapnia, and hypocapnia during the intervention period	through study completion, an average of 1 year
Pulmonary hypertension (PH) requiring iNO treatment, including PPHN within 7 days after birth and cPH after 28 days of life	through study completion, an average of 1 year
hsPDA (Iowa score ≥6 )	through study completion, an average of 1 year
The incidence of massive pulmonary hemorrhage, pneumothorax, pneumomediastinum, pneumopericardium, and ventilator-associated pneumonia(VAP)	through study completion, an average of 1 year
The incidence of Grade III to IV IVH according to Papile 1978 criteria	through study completion, an average of 1 year
The incidence of Necrotizing enterocolitis (NEC) > grade II according to Modified Bell's Staging Criteria	through study completion, an average of 1 year
The incidence of Culture-proven late-onset sepsis (onset after 72 hours of life)	through study completion, an average of 1 year
The incidence of Retinopathy of premature > grade II	through study completion, an average of 1 year
The duration of hospitalization	through study completion, an average of 1 year
Weight gain (g/kg/day)	through study completion, an average of 1 year
The incidence of discharge against medical advice (DAMA)	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Xingwang Zhu
• Collaborators: Hunan Provincial People's Hospital; First People's Hospital of Chenzhou; Kunming Children's Hospital; The Affiliated Hospital of Inner Mongolia Medical University; Hunan Children's Hospital; Guangdong Women and Children Hospital; Children's Hospital of Chongqing Medical University; Hunan Provincial Maternal and Child Health Care Hospital; Jiangxi Maternal and Child Health Hospital; Northwest Women's and Children's Hospital, Xi'an, Shaanxi; Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region; Inner Mongolia Maternal and Child Health Care Hospital; The Affiliated Hospital of Jining Medical University and Zaozhuang City; Quanzhou Women's and Children's Hospital; Women and Children's Hospital of Chongqing Medical University; Fujian Children's Hospital; Women and Children's Hospital of Ningbo University; Chongqing Qianjiang Central Hospital; Fuling Hospital of Chongqing University; Henan Children's Hospital Zhengzhou Children's Hospital; Moscow Regional Research Institute of Obstetrics and Gynecology named after Academician V. I. Krasnopolsky; People's Hospital of MeiShan; Qujing Maternal and Child Hospital; Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University; Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University; Shanxi Women and Children Hospital; Shenzhen Longhua Maternity and Child Health Care Hospital; Shijiazhuang Obstetrics and and Gynecology Hospital; Third Affiliated Hospital of Guangzhou Medical University; Zhangzhou Affiliated Hospital of Fujian Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 30, 2026

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Respiratory Distress Syndrome, Newborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiratory Distress Syndrome; Bronchopulmonary Dysplasia; Hyaline Membrane Disease
• Other Study ID Numbers: Combined Oscillation-Volume gu

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers who wish to use the data may apply by emailing the principal investigator with a comprehensive study protocol. After the primary results of this trial have been published, the full, de-identified dataset will be made available to all participating sites of COVES for secondary analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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