MINImising Total Radiation EXposure in Preterm Infants (MINI T-Rex)

Lung Ultrasound to Reduce the Number of Chest X-rays in Very Preterm Infants in the First 2 Weeks After Birth: A Randomised Controlled Trial

Being born too early (preterm birth) is the leading cause of death in children world-wide. In Australia, 97% of very preterm babies who are admitted to Neonatal Intensive Care Units need breathing support after birth to survive. Despite this significant global impact, neonatal clinicians have few tools available to guide breathing support. Currently, the only lung imaging tool that is routinely used in the Neonatal Intensive Care Unit is a chest X-ray. To reduce radiation exposure, chest X-rays are usually only performed one or two times a day. As chronic lung disease in babies who survive preterm birth is increasing, there is an urgent need to develop new ways to monitor the lungs of these fragile babies.

Lung ultrasound is a form of imaging that is fast, gentle and radiation free. However, it has not been routinely adopted into caring for preterm babies in most countries. This is because there are no randomised controlled trials that have demonstrated the benefit and safety of using lung ultrasound as the first-line imaging tool in preterm babies. The investigators will conduct a randomised controlled trial to demonstrate that lung ultrasound is a quick, safe and accurate alternative to chest x-rays in preterm babies.

Study Overview

• Status: Recruiting
• Conditions: PreTerm Neonate; Neonatal Respiratory Distress Syndrome
• Intervention / Treatment: Device: Lung ultrasound group; Diagnostic test: Standard Care

Detailed Description

Preterm babies are born with underdeveloped, fragile lungs and commonly develop respiratory distress syndrome. In Australia, 97% of preterm babies who are admitted to Neonatal Intensive Care Units need breathing support after birth. Respiratory support is vital to keep babies alive but is associated with short- and long-term lung damage. Unfortunately, many babies who survive preterm birth develop bronchopulmonary dysplasia (BPD), leading to poor health outcomes in adulthood.(2) Despite years of research, chronic lung disease is increasing.

Clearly, it is critical that clinicians have effective tools to guide breathing support. Currently, the only lung imaging tool that is routinely used in the Neonatal Intensive Care Unit is chest X-ray (CXR). The fundamental principle of use of ionising radiation in any population is to limit radiation exposure to as low as reasonably achievable (ALARA). To achieve this currently, the use of CXR is usually limited to once or twice a day. In addition CXR are performed by a specialised technician and are not always immediately available, delaying the time to diagnosis. Given the rapid and unpredictable changes in a preterm baby's lung disease, reliance on repeated CXR is fraught with risk. There is an urgent need to develop reliable tools that provides real-time and accurate feedback to guide breathing support in preterm babies.

New monitoring tools should be safe and improve outcomes. Lung ultrasound is a gentle form of lung imaging that is ideally suited for preterm babies. It is radiation free, readily available and does not require excessive handling of the baby. Ultrasound is already routinely used to image the brain and hearts of preterm babies and systems are available in all Neonatal Intensive Care Units in Australia. Several observational studies have demonstrated that lung ultrasound is accurate in diagnosing common neonatal respiratory disorders including pneumothorax, respiratory distress syndrome, transient tachypnoea of the newborn and the need for mechanical ventilation. Not all features of lung ultrasound are interchangeable with CXR measures of lung aeration in preterm infants. Lung ultrasound has a stronger relationship with an infant's respiratory support requirements than CXR. Only one study to date has assessed the ability of lung ultrasound to guide surfactant replacement in a randomized setting. Despite the growing body of evidence that lung ultrasound may be a suitable alternative to CXR, it has not been routinely adopted into clinical practice. This is because no randomized controlled trial has assessed the benefit and safety of using lung ultrasound as the first-line imaging tool in preterm babies. Furthermore, despite no evidence of benefit, some centres have already implemented lung ultrasound into routine practice. Before lung ultrasound can be widely implemented in preterm babies, it must be demonstrated to be beneficial and safe.

The investigators hypothesise that in preterm babies born <32 weeks' gestation, lung ultrasound will significantly reduce radiation exposure and be a safe alternative to CXR. This will be addressed by conducting an open label, randomised controlled trial at Joan Kirner Women's and Children's, Sunshine Hospital, Victoria.

The primary aim of this study is to evaluate whether the use of lung ultrasound as the primary lung imaging modality in preterm babies born <32 weeks' gestation reduces radiation burden.

Secondary aims include assessment of the safety and acceptability of lung ultrasound as the first line imaging tool, and additional signals of benefit including time to receive lung imaging and initiation of treatment, and duration of breathing support. To assess safety, the investigators will report the rate of key protocol defined adverse and serious adverse events in the intervention and control groups. Feasibility will be determined by protocol defined criteria for operational and clinical feasibility. Cost effectiveness will be determined by reporting the microcosts of each imaging tool and comparing the differential costs between the lung ultrasound and chest X-ray. Finally, the investigators will assess the acceptability to neonatal healthcare workers of lung ultrasound as the first-line imaging tool.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Arun Sett, PhD; Phone Number: +61405491595; Email: Arun.Sett@wh.org.au
• Study Contact Backup: Name: Niranjan Abraham, MD; Phone Number: 0413751479; Email: Niranjan.AbrahamWilliam@wh.org.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3021
      • Recruiting
      • Joan Kirner Women's and Children's, Sunshine Hospital, Western Health
      • Contact: Aun Sett, MBBS CCPU FRACP PhD; Phone Number: +6190552463; Email: Arun.Sett@wh.org.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All infants born <32 weeks' gestation and admitted to the neonatal intensive care unit (NICU) who require lung imaging for respiratory indications will be considered eligible. Each infant must meet all the following criteria to be enrolled in this study:

• The infant is born from 22 to 31+6 weeks' gestation by best obstetric estimate and admitted to the NICU
• The infant is considered to require lung imaging for respiratory indications
• The infant has a parent/guardian who can provide informed consent.

Exclusion Criteria

• The infant will only require CXR to be performed solely to confirm device position i.e. central line, endotracheal tube, gastric tubes
• The infant will only require CXR to be performed for specifically for non-respiratory indications i.e. assessment of cardiac silhouette
• The infant's Clinician has concern regarding clinical stability and tolerability of ultrasound scans
• The infant's skin integrity will not tolerate ultrasound gel
• Refusal of informed consent by their parent/guardian/legally acceptable representative
• The infant does not have a parent/guardian who can provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lung ultrasound group; Infants randomised to this group will have lung ultrasound as their first	Device: Lung ultrasound group; Infants in the intervention arm will receive lung ultrasound as their first line imaging. Clinicians will be permitted to order a chest x-ray if they require further information or if the lung ultrasound findings are inconclusive or not consistent with the clinical findings.
Active Comparator: Standard care; Infants in the standard arm will receive chest X-ray as their first form of lung imaging. Lung ultrasound will not be permitted in this group.	Diagnostic test: Standard Care; Infants in the standard group will receive chest X-ray as their first line imaging tool. Lung ultrasound will not be permitted in this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean difference in number of x-rays and radiation exposure in the intervention group	The total number of chest X-rays performed in the study period	Until day 14 of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean difference of X-rays for entire admission (until discharge or death)	Total number of x-rays performed from enrolment in study until death or discharge from hospital	From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months
The mean difference of X-rays and radiation exposure by gestational age at birth	The total number of CXR performed in the study period stratified by gestational groups (< 28 weeks' gestation and >/= to 28 weeks' gestation)	Until day 14 of life
Time to administering surfactant if clinically indicated	The mean difference in minutes to administer surfactant if clinically indicted between the lung ultrasound and chest x-ray groups	Until day 14 of life
Proportion of infants in the intervention arm who require CXR as first-line imaging due to lung ultrasound not being available	The number of CXRs performed after a lung ultrasound is performed in the intervention group due to the ultrasound clinicians or system not being available.	Until day 14 of life
Cost-effectiveness	The differential costs between the intervention and control groups determine from a time-in-motion analysis of a pre-determined sub sample of the study population (n=10 patients per group)	Until day 14 of life

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse event [1]	Oxygen requirement of fraction of inspired oxygen (FiO2) ≥20% of baseline for 2 hours or more after the lung imaging assessment	During or within 1 hour after each scheduled lung imaging assessment
Serious adverse event [2]	Acute oxygen desaturation (peripheral oxygen saturations [SpO2] <90%) that required the lung imaging to be terminated	During or within 1 hour after each scheduled lung imaging assessment
Serious adverse event [3]	Requirement of escalation of respiratory support	During or within 1 hour after each scheduled lung imaging assessment
Serious adverse event [4]	Apnoea requiring stimulation or other intervention that required the lung imaging to be terminated	During or within 1 hour after each scheduled lung imaging assessment
Serious adverse event [5]	For infants born <24 weeks' gestation, breech of skin integrity or skin irritation associated with lung imaging within 1 hour of imaging episode	Within 1 hours of each scheduled lung imaging assessment a photograph of the area will be taken and blindly scored using Hume-T scoring system
Serious adverse event [6]	Allocated imaging not being available and alternative imaging required	From the date of randomisation until 14 days
Adverse event [1]	Any death	During or within 24 hours after each scheduled lung imaging assessment
Adverse event [2]	Pulmonary haemorrhage	During or within 24 hours after each scheduled lung imaging assessment
Adverse event [3]	Administration of epinephrine or use of chest compressions	During or within 24 hours after each scheduled lung imaging assessment
Adverse event [4]	Unplanned extubation	During or within 1 hour after each scheduled lung imaging assessment
Adverse event [5]	In the intervention group, a significant delay in diagnosis and initiation of appropriate intervention for the following conditions due to lung ultrasound being inconclusive and a CXR being required to confirm diagnosis as determined by the clinical team: Significant pneumothorax; Significant pleural effusion; Severe respiratory distress syndrome requiring surfactant replacement therapy	Within first 2 weeks of age
Duration and level of mechanical ventilation and/or other respiratory support	Days of supplemental oxygen	From date of randomisation until death or discharge, whichever comes first, maximum 12 months
Duration of invasive and non invasive ventilation	Days of respiratory support including mechanical ventilation, continuous positive airway pressure and nasal high flow therapy	From date of randomisation until death or discharge, whichever comes first, maximum 12 months
Post natal corticosteroid use	Use of postnatal steroids, including types, timing and accumulated doses	From date of randomisation until death or discharge, whichever comes first, maximum 12 months
Incidence of Air leak	Incidence of pulmonary interstitial emphysema or pneumothorax	From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
Use of Volume expansion (crystalloid or colloid)	Total amount of volume expansion (in ml/kg) given during study duration	From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
Use of inotropic support	Maximum level of inotropic support given (drug and dose) during study duration	From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
Blood transfusion administration	Total blood transfused in ml/kg during study duration	From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
Incidence of patent ductus arteriosus	Incidence of patent ductus arteriosus requiring medical or surgical treatment during study duration	From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
Incidence of retinopathy of prematurity	Incidence of retinopathy of prematurity stratified by grade	From date of randomisation until death or discharge, whichever comes first, maximum 6 months
Incidence of necrotising enterocolitis	Incidence of Stage 2 or higher necrotising enterocolitis for study duration	From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
Incidence of intraventricular haemorrhage (IVH)	Incidence of IVH over entire admission	From date of randomisation until death or discharge, whichever comes first, maximum 6 months
Incidence of periventricular leukomalacia (PVL)	Incidence of PVL during entire admission	From date of randomisation until death or discharge, whichever comes first, maximum 12 months
Duration of admission	Duration of entire hospital admission u	From date of randomisation until death or discharge, whichever comes first, maximum 12 months
Diagnosis of BPD at 36 weeks	BPD status at 36 weeks defined by the standard oxygen reduction (ORT) test	From date of randomisation until death or discharge or 36 weeks post menstrual age, whichever comes first, maximum 36 weeks
Death	Survival status/date of death during hospital stay / cause and location of death	From date of randomisation until death or discharge or 36 weeks post menstrual age, whichever comes first, maximum 6 months

Collaborators and Investigators

• Sponsor: Western Health, Australia

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: May 15, 2025
• First Posted (Actual): May 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Lung ultrasound; Prematurity; Respiratory Distress Syndrome
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Premature Birth; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
• Other Study ID Numbers: 115953

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data will be shared to research parties who have a sound research proposal and prior institutional review board approval.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No