Selective High Frequency Oscillatory Ventilation (HFOV) for Neonates

Elective High Frequency Oscillatory Ventilation (HFOV) Versus Conventional Mechanical Ventilation(CMV) for Acute Respiratory Distress Syndrome(ARDS) and/or Respiratory Distress Syndrome(RDS) in Neonates：a Multicenter Randomized Trial

Neonatal respiratory distress syndrome (RDS) remains a major respiratory disorder for the increasing preterm population, and its incidence has been confirmed to be increased gradually with decreased gestational age. Previous studies demonstrated incidences of 90% at 24 weeks', 80% at 28 weeks', 57% at 30-31 weeks', and 25% at 35-36 weeks' gestational age(GA). However, these figures were mainly performed in the pre-neonatal acute respiratory distress syndrome (ARDS) era, in which ARDS was usually considered as RDS, and surfactant was therefore used repeatedly. In fact, no studies have indicated beneficial effects of surfactant for adult and pediatric ARDS, and therefore, its exact action for neonatal ARDS was needed to be further elucidated. In 2017, the international ARDS collaborative group provided the first consensus definition for neonatal ARDS, and the exact incidence of neonatal ARDS and mortality were unknown.

Study Overview

• Status: Withdrawn
• Conditions: Acute Respiratory Distress Syndrome; Respiratory Distress Syndrome; High Frequency Oscillatory Ventilation
• Intervention / Treatment: Device: Selective HFOV; Device: CMV

Detailed Description

Similarities to adult and pediatric ARDS, no special pharmacologic therapy for neonatal ARDS has been shown to reduce either short-term or long-term mortality and morbidity, the risk of death therefore remains high for preterm infants. Study reported that 50% chance of death with neonatal intensive care appeared at 24 weeks in most high-income countries and 34 in low-income and middle-income countries. Among the survivors, bronchopulmonary dysplasia(BPD), neurologic impairment and retinopathy of prematurity(ROP) were the main causes of secondary death, rehospitalization and medical resource use. How to reduce rate of mortality and severe complications constitutes a challenge for neonatologists.

An interesting result was that HFOV did reduce the incidence of mortality as compared with CMV(2:9 vs 3:3, 95%confidence intervel(CI) 0.09-0.89, P=0.03) (4:177 vs 13:179, 95%CI 0.10-0.94, P=0.04). The results suggested that, excluding preterm infants with RDS, HFOV could also reduce other primary outcomes, such as the risk of death, BPD, IVH and neurologic impairment.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Children's Hospital of Chongqing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 12 hours (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

subgroup 1: For a neonate to be included, the following four criteria must be fulfilled:

1. gestational age (GA) between 26+0 and 33+6 weeks (estimated on the postmenstrual date and early gestation ultrasonographic findings);
2. birth weight less than 2000g;
3. diagnosis with ARDS and/or RDS;
4. assisted with CMV within 12 h after birth;
5. stabilization before randomization within 12 h after birth: FiO2<0.40, Paw<12 cmH2O, 90%-95% of SpO2, pH>7.20, PaCO2<60 mmHg(these may be evaluated by arterial blood gas analysis).

subgroup 2 For a neonate to be included, the following four criteria must be fulfilled:

1. gestational age (GA) more than 33+6 weeks (estimated on the postmenstrual date and early gestation ultrasonographic findings);
2. birth weight more than 2000g;
3. diagnosis with ARDS and/or RDS;
4. assisted with CMV within 12 h after birth;
5. stabilization before randomization within 12 h after birth: FiO2<0.40, Paw<12 cmH2O, 90%-95% of SpO2, pH>7.20, PaCO2<60 mmHg(these may be evaluated by arterial blood gas analysis).

Exclusion Criteria:

Neonates with at least one of the following criteria are not eligible for the study:

1. neonates who only needed noninvasive ventilation;
2. major congenital anomalies or chromosomal abnormalities;
3. neuromuscular diseases;
4. upper respiratory tract abnormalities;
5. need for surgery known before the first extubation;
6. grade Ⅲ-IV-intraventricular hemorrhage (IVH);
7. congenital lung diseases or malformations or pulmonary hypoplasia.
8. parents reject to join

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selective HFOV; Selective HFOV will be provided	Device: Selective HFOV; Selective HFOV will only be provided with piston/membrane oscillators able to provide a real oscillatory pressure with active expiratory phase
Active Comparator: CMV; CMV will be provided	Device: CMV; CMV was delivered by time-cycled, pressure-limited ventilators

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death	the included neonates were dead	36 weeks' gestational age
the incidence of extracorporeal membrane oxygenation(ECMO) for neonates in group 2	the included neonates need to being supported by ECMO	36 weeks' gestational age
the incidence of bronchopulmonary dysplasia(BPD)	the included neonates were diagnosed with BPD	36 weeks' gestational age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of retinopathy of prematurity(ROP)	the included neonates were diagnosed with ROP	36 weeks' gestational age
the incidence of necrotizing enterocolitis(NEC)	the included neonates were diagnosed with NEC	36 weeks' gestational age
duration of invasive ventilation	duration of invasive ventilation for HFOV or CMV	36 weeks' gestational age
air leak (pneumothorax and/or pneumomediastinum) occurred	the included neonates were diagnosed with air leak	36 weeks' gestational age
intraventricular hemorrhage(IVH)>2nd grade	the included neonates were diagnosed with IVH>2nd grade	36 weeks' gestational age
composite mortality/BPD	the included neonates were diagnosed with composite mortality/BPD	36 weeks' gestational age
the success rate of extubation	the included neonates wean from invasive ventilation	36 weeks' gestational age

Collaborators and Investigators

• Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
• Collaborators: The First Affiliated Hospital of Anhui Medical University; LanZhou University; Beijing 302 Hospital; Peking University Third Hospital; Nanfang Hospital of Southern Medical University; Children's Hospital of Fudan University; Shanghai Children's Medical Center; Zhujiang Hospital; The First Hospital of Jilin University; Women's Hospital School Of Medicine Zhejiang University; Wuhan Union Hospital, China; People's Hospital of Xinjiang Uygur Autonomous Region; The Second Hospital of Shandong University; Nanjing Medical University; Second Affiliated Hospital of Guangzhou Medical University; First Affiliated Hospital of Xinjiang Medical University; Bethune International Peace Hospital; Kunming Children's Hospital; First Affiliated Hospital of Chongqing Medical University; First Affiliated Hospital of Harbin Medical University; Hunan Children's Hospital; Guangdong Women and Children Hospital; Xiamen Maternity & Child Care Hospital; Inner Mongolia People's Hospital; The Affiliated Hospital Of Southwest Medical University; The Children's Hospital of Zhejiang University School of Medicine; Jiangxi Province Children's Hospital; Mianyang Central Hospital; Zhengzhou Children's Hospital, China; Quanzhou Children's Hospital; Children's Hospital of Chongqing Medical University; Second Hospital of Lanzhou University; Tianjin Central Hospital of Gynecology Obstetrics; First Affiliated Hospital of Guangxi Medical University; The First People's Hospital of Yunnan; Shanxi Provincial Maternity and Children's Hospital; Yan'an Affiliated Hospital of Kunming Medical University; Children's Hospital of Nanjing Medical University; Third Affiliated Hospital of Zhengzhou University; Gansu Provincial Maternity and Child-Care Hospital; Affiliated Hospital of Southwest Medical University; Chongqing Maternal and Child Health Hospital; First Hospital of Tsinghua University; The First People's Hospital of Zunyi; Chengdu Women and Children's Center Hospital; Ningbo Women & Children's Hospital; Xianyang Children's Hospital; Jiulongpo No.1 People's Hospital; Children's Hospital of The Capital Institute of Pediatrics; Women and Children's Hospital, Branch of Chongqing Sanxia Central Hospital; Guangdong Academy of Medical Science and General Hospital; Women and Children's Health Hospital of Yulin; Women and Children Health Care Hospitalof GuangXi Zhuang Autonomous; Guiyang Maternal and Child Health Care Hospital; the Maternal and Child Health Hospital of Hainan Province; Maternal and Children's Healthcare Hospital of Taian; Shenzhen People's Hospital, The Second Medical College of Jinan University; Women and Children's Health Hospital of Qujing; The People's Hospital of Dehong Autonomous Prefecture; Yinchuan No 1 people's Hospital Affiliated of Ningxia Medical University; Women and Children Hospital of Qinghai Province; People's Liberation Army No.202 Hospital; Qinhuangdao Maternal and Child Health Care Hospital; Xuzhou Children Hospital; First Affiliated Hospital of Kunming Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): December 12, 2024
• Study Completion (Anticipated): December 12, 2024

Study Registration Dates

• First Submitted: November 7, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 9, 2018

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: NARDS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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