Clinical trial NCT03736707: Selective High Frequency Oscillatory Ventilation (HFOV) for Neonates
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome
High Frequency Oscillatory Ventilation
Lead sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Chongqing Medical University
name: Jiulongpo No.1 People's Hospital
name: Chongqing Maternal and Child Health Hospital
name: The First Affiliated Hospital of Anhui Medical University
name: Children's Hospital of The Capital Institute of Pediatrics
name: Peking University Third Hospital
name: First Hospital of Tsinghua University
name: Women and Children's Hospital, Branch of Chongqing Sanxia Central Hospital
name: First Affiliated Hospital of Chongqing Medical University
name: Quanzhou Children's Hospital
name: Xiamen Maternity & Child Care Hospital
name: Zhujiang Hospital
name: Nanfang Hospital, Southern Medical University
name: Guangdong Academy of Medical Science and General Hospital
name: Guangdong Women and Children Hospital
name: Women and Children's Health Hospital of Yulin
name: Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
name: Second Affiliated Hospital of Guangzhou Medical University
name: Guiyang Maternal and Child Health Care Hospital
name: The First People's Hospital of Zunyi
name: Lanzhou University Second Hospital
name: Gansu Provincial Maternal and Child Health Care Hospital
name: LanZhou University
name: First Affiliated Hospital of Harbin Medical University
name: First Affiliated Hospital of Xinjiang Medical University
name: Zhengzhou Children's Hospital, China
name: Third Affiliated Hospital of Zhengzhou University
name: the Maternal and Child Health Hospital of Hainan Province
name: Bethune International Peace Hospital
name: Wuhan Union Hospital, China
name: Children's Hospital of Nanjing Medical University
name: The First Hospital of Jilin University
name: Children's Hospital of Fudan University
name: Maternal and Children's Healthcare Hospital of Taian
name: The Second Hospital of Shandong University
name: Shanxi Provincial Maternity and Children's Hospital
name: Chengdu Women and Children's Center Hospital
name: The Affiliated Hospital Of Southwest Medical University
name: Affiliated Hospital of Southwest Medical University
name: Shenzhen People's Hospital, The Second Medical College of Jinan University
name: Tianjin Central Hospital of Gynecology Obstetrics
name: People's Hospital of Xinjiang Uygur Autonomous Region
name: Kunming Children's Hospital
name: The First People's Hospital of Yunnan
name: First Affiliated Hospital of Kunming Medical University
name: Yan'an Affiliated Hospital of Kunming Medical University
name: Women and Children's Health Hospital of Qujing
name: The People's Hospital of Dehong Autonomous Prefecture
name: The First People's Hospital of Yinchuan
name: The Children's Hospital of Zhejiang University School of Medicine
name: Women's Hospital School Of Medicine Zhejiang University
name: Beijing 302 Hospital
name: Hunan Children's Hospital
name: Women and Children Hospital of Qinghai Province
name: Jiangxi Province Children's Hospital
name: Inner Mongolia People's Hospital
name: Mianyang Central Hospital
name: People's Liberation Army No.202 Hospital
name: Ningbo Women & Children's Hospital
name: Shanghai Children's Medical Center
name: First Affiliated Hospital of Guangxi Medical University
name: Nanjing Medical University
name: Xianyang Children's Hospital
name: Qinhuangdao Maternal and Child Health Care Hospital
name: Xuzhou Children Hospital
First posted: 2018-11-09
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Neonates will be randomized and assigned either to selective HFOV or CMV
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: death
timeFrame: 36 weeks' gestational age
measure: the incidence of extracorporeal membrane oxygenation(ECMO) for neonates in group 2
timeFrame: 36 weeks' gestational age
measure: the incidence of bronchopulmonary dysplasia(BPD)
timeFrame: 36 weeks' gestational age
Secondary outcomes:
measure: the incidence of retinopathy of prematurity(ROP)
timeFrame: 36 weeks' gestational age
measure: the incidence of necrotizing enterocolitis(NEC)
timeFrame: 36 weeks' gestational age
measure: duration of invasive ventilation
timeFrame: 36 weeks' gestational age
measure: air leak (pneumothorax and/or pneumomediastinum) occurred
timeFrame: 36 weeks' gestational age
measure: intraventricular hemorrhage(IVH)>2nd grade
timeFrame: 36 weeks' gestational age
measure: composite mortality/BPD
timeFrame: 36 weeks' gestational age
measure: the success rate of extubation
timeFrame: 36 weeks' gestational age
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
Study officials:
References: