Speed of Lung Inflation During Ventilation of Extremely Preterm Infants

Not Applicable

Not yet recruiting

• Conditions: Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome in Premature Infant

• Registration Number: NCT07101419
• Lead Sponsor: Murdoch Childrens Research Institute

Brief Summary

Babies born extremely preterm (\<28 weeks of pregnancy) require support to breathe. Some babies require help to breathe from a breathing machine (mechanical ventilator). While this keeps babies alive, it may damage their lungs. To reduce this damage, doctors and nurses take particular care to try and provide the gentlest breathing support possible. However, evidence is still required to determine how to best support babies' breathing, whilst preventing lung damage and longer-term lung problems.

This clinical trial aims to compare two ways of adjusting a common setting on the breathing machine. This setting is called the pressure rise time or PRT. The PRT determines how quickly the breathing machine inflates a premature baby's lungs. A short PRT quickly inflates the lungs. A long PRT inflates the lungs more slowly. Previous research suggests that more slowly inflating the baby's lungs may cause less lung damage and still allow oxygen to be delivered to and carbon dioxide to be cleared from the lungs. However, larger studies are required to determine whether this should become the standard treatment.

This study investigates whether inflating the baby's lungs more slowly (long PRT) using the breathing machine is as effective as the PRT setting currently used (short PRT, more quickly inflating the lungs).

The main question it aims to answer is: Does how quickly the breathing machine inflates an extremely preterm baby's lung impact their oxygen levels?

Detailed Description

The FLOW-VENT trial will investigate if using a long pressure rise time (PRT; thereby reducing the speed of gas flow) compared to a short PRT, during synchronised, patient-triggered, volume-targeted conventional mechanical ventilation in extremely preterm infants within the first postnatal week impacts an infant's oxygenation.

All infants born extremely preterm (\<28 weeks' gestation) require breathing support to survive. However, this support can damage their lungs. Rates of bronchopulmonary dysplasia (BPD), the chronic lung disease of extreme prematurity, are increasing. This is despite 'lung protective' respiratory support and ventilation strategies that aim to minimise harm to the preterm lung.

Pre-clinical evidence suggests that gas flows lower than currently used during respiratory support of these infants may be a major, and easily modifiable way of reducing preterm lung injury (Tingay 2024; Bach 2012). Current guidelines lack evidence for suggested gas flow settings. Many ventilators now modulate ventilator gas flows by a setting known as pressure rise time (PRT).

FLOW-VENT is a prospective, multicentre, unblinded, randomised crossover trial enrolling 68 extremely preterm infants born \<28 weeks gestational age. A long PRT is defined as a PRT set at 75% of the inspiratory time (Ti). A short PRT is defined as a PRT set at 33% of the Ti.

Given the crossover design, infants will receive both the long and short PRT setting. Extremely preterm infants will be randomised to a 'sequence' which will determine the order in which they are exposed to the different PRTs; either:

* Long-Short PRT Sequence: Long PRT in the first treatment period and Short PRT in the second treatment period, OR

* Short-Long PRT Sequence: Short PRT in the first treatment period and Long PRT in the second treatment period.

The trial crossover phase (\~10-12 hours) consists of: 1) Preparatory washout period (1 to 2 hours); 2) First treatment period (4-hours); 3) Washout period (1 to 2 hours); 4) Second treatment period (4-hours). Following this, there is a 12-hour follow-up period to monitor for adverse/safety events. The primary outcome (average S/F ratio) is assessed only during the 4-hour treatment periods.

Results from this trial will inform the decision to proceed to a larger randomised trial, powered for longer term respiratory outcomes (e.g. time to extubation from mechanical ventilation, BPD at 36 weeks' postmenstrual age).

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-28
• Study First Submitted QC: 2025-07-28
• Last Update Submitted: 2025-07-28
• Study First Posted: 2025-08-03
• Last Update Posted: 2025-08-03
• Study Start: 2025-09-01
• Primary Completion: 2027-08
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

• Admitted to participating neonatal intensive care unit
• Born between 22+0 to 27+6 weeks' gestation
• Current weight ≥400 grams
• Receiving synchronised, patient-triggered, volume-targeted (all breaths) conventional mechanical ventilation (Pressure Control-Assist Control + Volume Guarantee [PC-AC+VG] mode on Dräger Babylog VN500/800 ventilators) initiated within 72-hours post birth
• Postnatal age ≥6 hours and ≤7 days
• Received surfactant therapy
• Clinically stable (as per treating and research team consensus)
• Parent(s)/legal guardian provides prospective informed consent.

Exclusion Criteria

• Major congenital anomaly involving the cardiac, respiratory or gastrointestinal systems, or a known genetic syndrome or diagnosis that might affect respiratory course and outcomes
• Severe pulmonary hypoplasia due to anhydramnios or oligohydramnios before 22 weeks in which the neonatal consultant anticipates that pulmonary hypoplasia related respiratory failure will be the major respiratory problem in early postnatal life
• Receiving (or expected to receive within the next 12 hours) any other mode of mechanical ventilation including synchronised intermittent mandatory ventilation (SIMV), pressure support ventilation (PSV) or high-frequency oscillatory ventilation
• Planned for extubation from mechanical ventilation within the next 12 hours.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Change in peripheral oxygen saturation to fraction of inspired oxygen ratio (S/F Ratio) measured each minute during each treatment period (0 minutes to 4 hours)	0 minutes then each minute up to 4 hours for each of the Long PRT and Short PRT 4-hour treatment periods

Secondary Outcome Measures

Name	Time	Method
Change in pressure rise time (PRT) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in mean airway pressure (MAP) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during of the Long PRT and Short PRT 4-hour treatment periods.
Change in positive end expiratory pressure (PEEP) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in peak inspiratory pressure (PIP) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in tidal volume (VT) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in respiratory rate measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in minute ventilation measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in endotracheal tube leak measured each minute during each treatment period (0 minutes to 4 hours)	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in inspiratory time (Ti) measured each minute during each treatment period (0 minutes to 4 hours)	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in inspiratory gas flows measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in peripheral oxygen saturation (SpO2) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in fraction of inspired oxygen (FiO2) measured each minute during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Change in incidence of significant oxygen desaturation measured during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.	Significant oxygen desaturation is defined as SpO2 \<80% for \>30 seconds
Change in total number FiO2 changes measured during each treatment period (0 minutes to 4 hours).	Measured during each of the Long PRT and Short PRT 4-hour treatment periods.
Incidence of air leak (pneumothorax or pneumomediastinum)	Completed for each participant at end of their study period: 22-24 hours from study commencement.
Incidence of pulmonary haemorrhage receiving management (increased PEEP/PIP/FiO2 or blood products)	Completed for each participant at end of their study period: 22-24 hours from study commencement.
Incidence of resuscitation (defined as receiving external cardiac compressions or adrenaline boluses)	Completed for each participant at end of their study period: 22-24 hours from study commencement.
Incidence of death	Completed for each participant at end of their study period: 22-24 hours from study commencement.
Incidence of treating consultant request to discontinue randomly allocated PRT prematurely	Completed for each participant at end of their study period: 22-24 hours from study commencement.

Trial Locations

Locations (3)

Mercy Hospital for Women; 🇦🇺 Heidelberg, Victoria, Australia

The Royal Women's Hospital; 🇦🇺 Parkville, Victoria, Australia

Joan Kirner Women's and Children's Hospital; 🇦🇺 Saint Albans, Victoria, Australia