Selective High Frequency Oscillatory Ventilation (HFOV) for Neonates

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Respiratory Distress Syndrome, Acute Respiratory Distress Syndrome, High Frequency Oscillatory Ventilation

Intervention / Treatment
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* Device: Selective HFOV
* Device: CMV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subgroup 1: For a neonate to be included, the following four criteria must be fulfilled: gestational age (GA) between 26+0 and 33+6 weeks (estimated on the postmenstrual date and early gestation ultrasonographic findings); birth weight less than 2000g; diagnosis with ARDS and/or RDS; assisted with CMV within 12 h after birth; 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: gestational age (GA) more than 33+6 weeks (estimated on the postmenstrual date and early gestation ultrasonographic findings); birth weight more than 2000g; diagnosis with ARDS and/or RDS; assisted with CMV within 12 h after birth; 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: neonates who only needed noninvasive ventilation; major congenital anomalies or chromosomal abnormalities; neuromuscular diseases; upper respiratory tract abnormalities; need for surgery known before the first extubation; grade Ⅲ-IV-intraventricular hemorrhage (IVH); congenital lung diseases or malformations or pulmonary hypoplasia. parents reject to join

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 12 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Neonates will be randomized and assigned either to selective HFOV or CMV
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |