Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lung ultrasound group | Experimental | Infants randomised to this group will have lung ultrasound as their first |
|
| Standard care | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lung ultrasound group | Device | 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. |
| 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 |
| 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 |
| 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] |
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:
Exclusion Criteria
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Arun Sett, PhD | Contact | +61405491595 | Arun.Sett@wh.org.au | |
| Niranjan Abraham, MD | Contact | 0413751479 | Niranjan.AbrahamWilliam@wh.org.au |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Joan Kirner Women's and Children's, Sunshine Hospital, Western Health | Recruiting | Melbourne | Victoria | 3021 | Australia |
De-identified individual patient data will be shared to research parties who have a sound research proposal and prior institutional review board approval.
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012127 | Respiratory Distress Syndrome, Newborn |
| D012128 | Respiratory Distress Syndrome |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D007235 | Infant, Premature, Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Clinicians and participants will be unblinded to the study intervention. All outcome analysis will be performed blinded to the study intervention.
|
| Standard Care | Diagnostic Test | 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. |
|
| 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 |
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:
| 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 |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |