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

Army Medical University of People's Liberation Army

Status: Enrolling

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

Treatments: Device: CMV; Device: HFOV

Study type: Interventional

Funder types: Other

Identifiers

NCT03736707

CSTB2024NSCQ-MSX0158 (Other Identifier)

HFOV for perinatal ARDS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 400 estimated patients

Sex: All

Ages: 1 minute to 1 hour old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

1. GA was between 24+0 and 31+6 weeks.
2. Preterm neonates were admitted to NICU within 1 hours after birth, diagnosed with perinatal ARDS using Montreux guidelines and stable supported by CMV.
3. Stabilization for 2 hours before randomization: FiO2 0.40, mean airway pressure (MAP) 10-14 cmH2O, ≤ 40 bpm of respiratory rate, 90%-94% of SpO2, pH > 7.20, PaCO2 60 mmHg, tidal volume of 5 ml/kg and > 35% of hematocrit (these may be evaluated by arterial blood gas analysis).

Exclusion criteria

Neonates were not included if any of the following criteria were met:

1. Parents or guardians' decision not to participate.
2. Major congenital anomalies or chromosomal abnormalities
3. Need for surgery or more than grade 2nd of IVH before randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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400 participants in 2 patient groups

high frenquency oscillation ventilation (HFOV)

Experimental group

Description:

HFOV + volume guarantee (VG) as the intervention group HFOV was provided only with piston or membrane oscillators capable of delivering true oscillatory pressure with an active expiratory phase (i.e., Acutronic FABIAN-III, SLE 5000, Löwenstein Med LEONI+, or Sensormedics 3100A). Other machines offering high frequency ventilation were excluded. The lung recruitment maneuver was performed as previously described,15 and lung volume was assessed by chest radiography or lung ultrasound, targeting the right diaphragm at the level of 8th-9th rib (or 7th-8th rib in case of air leak). Crossover between HFOV and CMV This study allowed infants who failed to respond to their assigned ventilation mode to receive a trial of the alternate mode. Crossover criteria for HFOV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or signs of ventilator-induced cardiac output reduction. Non-responders to HFOV were switched to CMV.

Treatment:

Device: HFOV

conventional mechanical ventilation (CMV)

Active Comparator group

Description:

CMV was delivered by time-cycled, pressure-limited ventilators. Only pressure regulated volume control (PRVC) will be provided by any type of neonatal ventilator. Crossover criteria for CMV-assigned neonates included failure for 3 hours to maintain SpO2 ≥ 50% despite FiO2 of 1.0, PaCO2 \> 60 mmHg for 3 hours, or requiring \> 30 cm H2O PIP to sustain ventilation. Non-responders to CMV were switched to HFOV. in both groups, ventilator settings were adjusted at the discretion of the attending clinician to maintain a SpO2 between 90%-94%, a PaO2 between 50 and 80 mm Hg and a PaCO2 between 35 and 60 mm Hg and a pH between 7.20 and 7.45. PO2 and PCO2 levels were monitored using arterial blood gas analysis and/or transcutaneous monitoring.

Treatment:

Device: CMV