Clinical trial NCT06975189: MINImising Total Radiation EXposure in Preterm Infants
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Neonatal Respiratory Distress Syndrome
PreTerm Neonate
Keywords: Lung ultrasound
Respiratory Distress Syndrome
Prematurity
Lead sponsor: Western Health, Australia
Sponsor class: OTHER_GOV
First posted: 2025-05-16
Enrollment: 180
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The mean difference in number of x-rays and radiation exposure in the intervention group
timeFrame: Until day 14 of life
Secondary outcomes:
measure: The mean difference of X-rays for entire admission (until discharge or death)
timeFrame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months
measure: The mean difference of X-rays and radiation exposure by gestational age at birth
timeFrame: Until day 14 of life
measure: The sensitivity and specificity of lung ultrasound for specific respiratory disorders as defined by the final clinical diagnosis
timeFrame: Until day 14 of life
measure: Time to administering surfactant if clinically indicated
timeFrame: Until day 14 of life
measure: Proportion of infants in the intervention arm who require CXR as first-line imaging due to lung ultrasound not being available
timeFrame: Until day 14 of life
measure: Cost-effectiveness
timeFrame: Until day 14 of life
Other outcomes:
measure: Serious adverse event [1]
timeFrame: During or within 1 hour after each scheduled lung imaging assessment
measure: Serious adverse event [2]
timeFrame: During or within 1 hour after each scheduled lung imaging assessment
measure: Serious adverse event [3]
timeFrame: During or within 1 hour after each scheduled lung imaging assessment
measure: Serious adverse event [4]
timeFrame: During or within 1 hour after each scheduled lung imaging assessment
measure: Serious adverse event [5]
timeFrame: 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
measure: Serious adverse event [6]
timeFrame: From the date of randomisation until 14 days
measure: Adverse event [1]
timeFrame: During or within 24 hours after each scheduled lung imaging assessment
measure: Adverse event [2]
timeFrame: During or within 24 hours after each scheduled lung imaging assessment
measure: Adverse event [3]
timeFrame: During or within 24 hours after each scheduled lung imaging assessment
measure: Adverse event [4]
timeFrame: During or within 1 hour after each scheduled lung imaging assessment
measure: Adverse event [5]
timeFrame: Within first 2 weeks of age
measure: Duration and level of mechanical ventilation and/or other respiratory support
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 12 months
measure: Duration of invasive and non invasive ventilation
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 12 months
measure: Post natal corticosteroid use
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 12 months
measure: Incidence of Air leak
timeFrame: From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
measure: Use of Volume expansion (crystalloid or colloid)
timeFrame: From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
measure: Use of inotropic support
timeFrame: From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
measure: Blood transfusion administration
timeFrame: From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
measure: Incidence of patent ductus arteriosus
timeFrame: From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
measure: Incidence of retinopathy of prematurity
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 6 months
measure: Incidence of necrotising enterocolitis
timeFrame: From date of randomisation until death or 2 weeks of age, whichever comes first, 2 weeks
measure: Incidence of intraventricular haemorrhage (IVH)
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 6 months
measure: Incidence of periventricular leukomalacia (PVL)
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 12 months
measure: Duration of admission
timeFrame: From date of randomisation until death or discharge, whichever comes first, maximum 12 months
measure: Diagnosis of BPD at 36 weeks
timeFrame: From date of randomisation until death or discharge or 36 weeks post menstrual age, whichever comes first, maximum 36 weeks
measure: Death
timeFrame: From date of randomisation until death or discharge or 36 weeks post menstrual age, whichever comes first, maximum 6 months
Locations:
Study officials:
References: