Clinical trials

Background: In children with \>120 rare diseases, haematopoietic stem cell transplant (HSCT) provides a medical "reset" for the body, replacing diseased or dysfunctional bone marrow with healthy donor-derived stem cells following high-dose chemotherapy and/or radiotherapy. However, severe and fatal complications are common with HSCT. There has been a lack of properly conducted clinical trials to decrease mortality and morbidity. Traditional randomised controlled trials (RCTs) have several critical limitations in children undergoing HSCT, including population heterogeneity, restrictive eligibility criteria and slow enrolment. Adaptive platform trials (APTs) may overcome these limitations through enhanced trial efficiency by sharing a control group, reducing sample size and allowing continuous learning from accumulating data. APTs also allow simultaneous evaluation of distinct interventions at different timepoints and in multiple subgroups of participants, facilitating tailored approaches across heterogeneous populations. When an intervention proves superior, it becomes the new standard of care, allowing additional interventions to be introduced. To improve outcomes, we have developed an international APT - BANDICOOT. This trial will continuously enrol children and adolescents receiving HSCT and allow the assessment of multiple novel interventions simultaneously. The goal is to accelerate research findings, reduce duplication of efforts, and improve patient outcomes. Objectives: The primary objective of BANDICOOT is to determine the effectiveness of a range of interventions to improve HSCT outcomes for children and adolescents. The secondary objectives include: * Assessing the cost-effectiveness of trial interventions * Assessing the safety of a range of interventions to improve HCT outcomes * Collection of a core data set for participants consenting to the platform regardless of domain eligibility. Study design: BANDICOOT is a prospective, pragmatic, adaptive platform trial with interventions organised into domains. Domains may be open-label or blinded. Study population: The trial population will be children aged 1-week old to 18 years old who are receiving an HSCT. Trial outcomes: The primary outcome is an ordinal scale of HSCT outcomes based on organ support, viraemia, immune reconstitution and relapse status censored at Day 100 post HSCT. The selection and grading of components within this ordinal endpoint was informed by a formal endpoint development process, described in detail by Walker et al, 2025 (see References). Interventions: Multiple interventions will be evaluated in BANDICOOT across multiple treatment modalities (domains). New interventions will be added over time, and interventions may be dropped for futility or included in standard care as the study progresses. The details of the interventions will be provided in separate clinicaltrials.gov Study Records, linked to this Master record. Abbreviated methods: Inferences in this trial will be based on a Bayesian statistical model. The primary outcome will be analysed using a multinomial model with a cumulative logistic link, which is an extension of a binary logistic model to account for ordinal outcomes with more than two categories, and is commonly known as the 'proportional odds' model. Secondary outcomes will be analysed with parametric models specific to the type of outcome (e.g., the Bernoulli model with a logistic link for binary endpoints).

TABLO (Tranexamic Acid to reduce Blood Loss after varus derotation Osteotomy) is a clinical trial of postoperative tranexamic acid vs placebo in non-ambulatory children with cerebral palsy (CP) undergoing reconstructive hip surgery. Improving surgical outcomes is a high priority in this patient population given the high risk of bleeding and the diminished capacity for these children to withstand substantial blood loss. Preliminary data from the study institution indicates that approximately one third of these patients receive transfusion of blood products in the postoperative period. There is growing evidence that hidden blood loss occurring in the postoperative period is substantial and can potentially be attenuated with the administration of Tranexamic Acid (TXA). However, trials on postoperative TXA have been carried out exclusively in adult surgical populations.

The goal of this clinical trial is to compare the effect of live music therapy and recorded music on recovery of consciousness in children aged 1 to 18 years who have a disorder of consciousness (DoC) after a severe brain injury. Researchers also want to learn how children respond during music and noise, whether early responses to music are linked to recovery at 6 months, and how parents experience music therapy during their child's hospital stay at The Royal Children's Hospital (RCH) in Melbourne. Participants will: * Take part in a 10-day study period while in hospital. On 8 of the 10 days, they will receive either live or recorded familiar music in random order. Their level of consciousness will be measured before and after each session using a simple behavioural checklist. On the other 2 days, they will take part in video-recorded sessions to compare behavioural responses during live music, recorded music, and white noise. Videos will help capture small changes in movement, eye gaze, or facial expression. * Have their level of consciousness checked again at 6 months after injury to see if early responses relate to later recovery. Parents and caregivers will be invited to take part in an interview about their experiences and observations of music therapy with their child. This study will help researchers understand whether live music therapy provides benefits beyond recorded music and will guide how music therapy is best used to support children and families during recovery from severe brain injury.

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?

This project will study the effect of the TAG TEAM group CBT program on the mental health of trans and gender diverse adolescents. TAG TEAM was co-designed by researchers and clinicians with a group of trans and gender diverse young people to help trans and gender diverse adolescents understand and cope with minority stress. Minority stress includes experiences like discrimination and rejection. TAG TEAM focuses on learning and practicing skills to support mental health and wellbeing. It also includes group discussions and activities with other trans and gender diverse young people. TAG TEAM groups are run by a psychologist and a trans peer facilitator. A trans peer facilitator is a trans and gender diverse person who is there to share their experience of being trans and to support participants in the group sessions.

Individuals with rare genetic conditions may experience a delay or loss of developmental skills. Many have limited verbal speech. The aim of this clinical trial is to examine how well a speech-generating device supports the communication skills of participants with a rare genetic condition. The speech-generating device is a communication program loaded onto an iPad. This is a crossover trial, meaning that each participant will receive both the treatment (device) and a control (usual care; no device) phase. The order in which each participant receives the device versus the usual care (no device) will depend on which group the participant is assigned to. The changes in communication in each phase will then be compared. During the trial, participants can expect to complete a series of assessments and attend a total of 2 x 1-hour therapy session per week for 6 weeks.

Many babies born very preterm (\<32 weeks of pregnancy) require support to breathe from a breathing machine (mechanical ventilator) via a breathing tube. Although this keeps babies alive, it can damage their lungs. To reduce this damage, doctors and nurses try to change babies to gentler breathing support that does not require a breathing tube. This is usually done using a method called nasal continuous positive airway pressure (nCPAP) that uses a nosepiece to deliver breaths. This process of removing the breathing tube is called "extubation". Many babies will need the breathing tube put back in after extubation (for various reasons) and this is independently associated with poorer outcomes. This research study aims to compare two ways of performing extubation - both of which are already used regularly by doctors and nurses. The "standard extubation" approach involves taking a baby's breathing tube out first, then applying the nosepiece and starting nCPAP. The more recent approach, called "prePAP", involves applying the nosepiece and starting nCPAP before taking the breathing tube out. Previous research suggests that a prePAP approach may provide better support for babies during extubation. However, larger studies are required before this approach is more commonly used. This study is investigating whether extubating the baby with prePAP is better than extubating the baby without prePAP. The main question it aims to answer is: Does initiating nCPAP before extubation in very preterm babies reduce the fall in their oxygen levels post-extubation?

Parents and caregivers of children who have a chronic condition carry a large care burden and are at higher risk of having mental health symptoms. This study aims to see if completion of a mental health questionnaire by parents / caregivers at or before the child's paediatric appointment can help identify any symptoms of stress, anxiety or depression. Following the questionnaire, parents / caregivers will be provided with the results of the questionnaire along with an information resource sheet. This will include information on anxiety, stress and depression, as well as different agencies they can contact to get support. Parents / caregivers will be followed up at 3 and 6 months to see if they have any changes to mental health and quality of life, and whether they accessed any support services. Participants who did not complete the 3-month survey will be asked at the 6-month clinic visit to provide responses on an iPad to up to 5 questions selected from the 3-month survey. A text message will be sent prior to the visit to inform them. The primary aim for this trial is to see whether parents / caregivers find this process acceptable, and whether it can work in a busy hospital clinic.

Recent studies have demonstrated that growth of vascular malformations can be driven by genetic variants in one of 2 signalling pathways. Targeted drugs specific to these pathways have been developed and shown to be effective in treating cancer. This study will describe the effectiveness of (i) 48 weeks of alpelisib therapy for participants with slow-flow vascular malformations and a gene mutation in one of these signalling pathways (module 1) and (ii) 48 weeks of mirdametinib therapy for participants with fast-flow vascular malformations and a gene mutations in the other signalling pathway (module 2).

A challenge to intermittent vancomycin dosing in young infants is the avoidable delay caused by the need to wait until steady state (i.e. when the drug concentrations are in equilibrium) to measure a vancomycin concentration, as this generally occurs 24 to 48 hours after starting treatment. If the target concentration is not achieved, the dose needs to be adjusted, resulting in further delays in an infant achieving the concentration required to treat their infection. The purpose of this study is to assess the use of early therapeutic drug monitoring (first-dose trough) and, if needed, early dose adjustment, in achieving target vancomycin concentrations at steady state. A dose adjustment calculator (available through a web application) will be used to determine the need for dose adjustment (based on predicted steady state concentration) and recommend an adjusted dose if required.

The aim of the StopStop@HITH study is to see if stopping antibiotics when symptoms stop is as good as finishing the course of antibiotics. The study will enrol children at the Royal Children's Hospital who are prescribed oral antibiotics after completing a course of intravenous (IV) antibiotics for the treatment of cellulitis, urinary tract infection (UTI), lower respiratory tract infection (LRTI) and lymphadenitis. The aims of the study are: * To determine if oral antibiotics can be safely stopped once symptoms stop in children with cellulitis (who have completed a course of IV antibiotics). * To assess feasibility of a larger study of other common infections across multiple hospitals. The participants parent/guardian will complete a daily symptom tracker for the duration of the prescribed oral antibiotic course and attend a telehealth appointment with the study team once the participants symptoms have resolved. There are additional follow up surveys at day 14, day 28 and day 180.

Infants born preterm (before 36 weeks' gestation age) have immature lungs and struggle to breathe on their own. They are supported via respiratory machines like ventilators, as well as pharmaceutical aids like surfactant replacement therapy. Surfactant replacement therapy is an established therapy for the treatment of respiratory distress syndrome, which is a common illness in infants born preterm. Surfactant replacement therapy can be delivered to an infant's lungs a few ways, including via a small tube that is briefly placed down an infant's throat. This is considered the least invasive method currently available, and is becoming more popular. It is referred to as minimally invasive surfactant therapy (MIST). A baby can receive surfactant via MIST if they are receiving non-invasive respiratory support, like from a continuous positive airway pressure (CPAP) machine. Doctors and researchers are looking for simple ways to make MIST more effective. This clinical trial will investigate if briefly increasing the air pressure delivered by a CPAP machine before giving MIST therapy will make MIST more effective. This strategy is called a lung recruitment manoeuvre (LRM), because it opens up more of the lungs - 'recruits' them - to help with oxygenation. The CPAP setting that is briefly changed is called positive end expiratory pressure (PEEP) - it increases the amount of air left in the lungs at the end of a breath. This stops parts of the lung collapsing when exhaling, which commonly occurs in the lungs of infants born preterm as they are immature. The goal of this clinical trial is to investigate if a LRM prior to MIST improves ventilation and lung aeration in preterm infants born 24-32 weeks' gestation. The main question it aims to answer is: How a LRM prior to MIST might impact patterns of ventilation and lung aeration in preterm infants, compared to no LRM prior to MIST. The current standard of care is no LRM before MIST. Researchers will compare this current standard against a LRM before MIST to see if it potentially improves patterns of ventilation. Participants will be randomly placed (by chance) to receive either no LRM before MIST (control) or a LRM before MIST (intervention). Participants will be randomised once their treating clinical team have decided to give MIST.

This is a small trial testing out a new approach before doing a bigger study. Researchers are observing a group of children/adolescents (ages 5-17) with acute lymphoblastic leukemia (ALL) and testing a physical activity and exercise program on a group of them who after 5 weeks of treatment show signs of weakness or frailty. Kids who are NOT losing muscle aren't part of the exercise trial - they're just monitored over time to see how they do. The goal: To see if an exercise program helps kids who are getting weaker from acute lymphoblastic leukemia treatment build back/maintain their strength, compared to kids who don't do the extra intervention. The study will also look at if this way of measuring muscle weakness works well for kids with cancer.

The goal of this clinical trial is to learn if an ultrasound scan using artificial intelligence can accurately screen for hip dysplasia. Researchers will compare the artificial intelligence ultrasound results to the standard ultrasound measures to see if the artificial intelligence ultrasound scan can accurately screen for hip dysplasia. It will also seek to understand how parents feel about their children undergoing this scan. Participants will: * Have an additional ultrasound performed on their child at their scheduled outpatient's appointment for hip dysplasia * Complete a short questionnaire about the experience of having the measurement performed on their child

This study is being conducted at seven major children's hospitals in Australia and New Zealand to test a new approach for treating a virus, called cytomegalovirus in children with weakened immune systems. The researchers want to find out if using a web app to customise the dose of a medication called ganciclovir is better at clearing the virus over a six-week period compared to the standard method of giving the medication.

Jack Jumper ant (JJA) venom allergy is a uniquely Australian medical condition. It is the leading cause of venom allergy and affects up to three per cent of the population. 70 percent of people with JJA allergy will have another reaction on a repeat sting and this sensitivity appears to persist for many years. Venom immunotherapy (VIT) has been shown to be a safe and effective treatment in the prevention of severe systemic allergic reactions (anaphylaxis) to future stings. It is currently offered to patients as standard care in Tasmania, South Australia and Victoria. However, whilst JJA VIT has been used for many years, there is a lack of evidence on the long-term benefit of the treatment and how it impacts patient quality of life. This trial will offer patients who have completed a JJA VIT program (between 3 and \< 6-years duration) and have been off-treatment for at least 18-months and \< 5 years, to have a supervised JJA sting challenge and blood test to assess their JJA venom tolerance level. It will also ask them to complete a set of questionnaires at different timepoints to obtain a history of their exposure and reactions to JJA stings outside of the hospital setting (field stings), and to measure the impact of the completed VIT and knowledge of their sting challenge outcome on their quality of life and their behaviours around auto-injectors. These measures will be used to explore the long-term effectiveness of JJA VIT and the impact of a sting challenge post VIT on a patient's quality of life.

This study aims to evaluate the efficacy of genotype-informed Bayesian dosing of tacrolimus in optimising drug exposure among paediatric solid organ transplant recipients. By tailoring tacrolimus dosage based on individual genetic makeup and using Bayesian modeling to predict drug levels, the researchers hope to increase the likelihood of achieving therapeutic drug concentrations while minimising the risk of adverse events associated with subtherapeutic or supratherapeutic exposure.

This is a mixed-methods program evaluation from a health systems and policy perspective, involving (i) stakeholder analysis, (ii) policy-implementation gap analysis, and (iii) comparative country case studies. This study aims to understand how national oxygen strategies achieve impact at national, and subnational level, across country contexts, at what cost. The the investigators seek to: 1. Involve policymakers, implementers (including private sector), and medical oxygen users in identifying challenges and understanding potential solutions to medical oxygen access; 2. Generate new data on how medical oxygen systems work and can be improved from multiple perspectives; 3. Draw lessons on medical oxygen that can directly inform national and global practice and policy. This study will be conducted in 6 of the 9 countries participating in the Clinton Health Access Initiative (CHAI) led Medical Oxygen Implementation (MOXY) program (Uganda, Nigeria, Rwanda, Liberia, Lao PDR, Cambodia). Key informants will be selected representing government, non-governmental agencies, professional associations, private sector, and civil society. This study will be completed over 4 years, with timelines varying between country study sites.

The goal of this observational study is to learn about the long-term outcomes of children and young people who underwent an 18-month course of oral immunotherapy (OIT) treatment for peanut, egg or milk allergy. It aims to: • Compare long-term changes in health-related quality of life (HRQL) at 5-15 years after stopping OIT in participants who achieved remission and those who did not. Participants will attend a single follow-up visit for: * A blood test * Skin prick test (SPT) * Allergy questionnaires

The goal of this pilot study is to explore the feasibility and acceptability of a medicinal cannabis clinical trial into easing the symptoms of children undergoing palliative care for non-oncological conditions. The trial will evaluate the study design including recruitment strategy, medication tolerability, duration and outcomes to determine acceptability and feasibility for participating families. The data collected will then be used to design a full-scale multi-centre trial. Participants will be randomly allocated to receive one of two medicinal cannabis products. Neither the participants nor researchers will know the study drug allocation until the end of the trial.

The current standard of care for paediatric patients with cancer regarding preservation of their fertility (FP) is to provide high-quality information during the clinical consultation process. However, this approach depends on health provider knowledge and communication and has been shown to be sub-optimal in some situations. This impairs the critical decision-making of patients regarding fertility testing, utilization of gametes, and continuing payment of storage fees. The fertility preservation decision aid (FP DA) may lead to a greater understanding of their fertility status for participants. This knowledge may allow participants the opportunity to assess potential fertility issues prior to the end of their reproductive window, helping to minimize missed opportunities for parenthood. This research study aims to assess the effectiveness of the use of the FP DA on unmet fertility information needs when it is provided in addition to high-quality information in parents of cancer survivors and CAYA cancer survivors compared to high-quality information alone.

Urinary tract infections (UTI) are commonly encountered in children, with 7% diagnosed with at least one UTI by the age of 19 years. The evidence for treatment of uncomplicated UTI is clear; oral antibiotics are as good as intravenous (IV) antibiotics, usually for a total of 7 days. Complicated UTIs (cUTIs) on the other hand, are common reasons for hospital admissions for IV antibiotics and constitute a major burden for healthcare systems. There is considerable variation in care for children who present with UTI and have complicating features such as vomiting, dehydration, urological abnormalities or have a previous history of UTI. Australian and international guidelines lack clear, evidence-based recommendations to guide treatment in this group. Without gold standard evidence, these children will continue to receive unnecessary IV antibiotics, longer hospital stays and poorer health outcomes. This multicentre, non-inferiority randomised trial will investigate if One dose - single dose of IV followed by 2 days oral antibiotics is as non-inferior to Three doses for children with UTI and co-existing complicating factors presenting to the Emergency Department (ED). In other words, this study will compare if a single dose of IV antibiotics plus two days oral antibiotics is as clinically effective as 3 doses antibiotics in resolving UTI symptoms at 72 hours after the first dose of IV antibiotics, for complicated UTIs in children presenting to the ED. All participants will receive a total of 7 days of antibiotics for the complicated urinary tract infection. If 1 dose IV and 2 days oral antibiotics is found to be as good as 3 days, the duration of IV antibiotics for complicated UTI can be reduced along with avoidance of the inherent risks of unnecessary hospital admission by administering a single IV dose in an outpatient/ED setting. On the other hand if a single IV dose results in prolonged symptoms or treatment failure, this will inform practice for the proportion of children who have a single dose of IV antibiotics in the ED and are sent home on oral antibiotics. Regardless of the outcome, this trial will inform clinical practice for complicated UTI to improve health outcomes for this group.

Data collection study to establish a predictive model of infection observed during childhood cancer therapy using data captured by wearable technology.

This is a multi- centre trial of children with bone and joint infections (BJIs) at eight major paediatric hospitals in Australia and New Zealand. The primary objective is to establish if in children with acute, uncomplicated BJIs, entirely oral antibiotic treatment is not inferior to initial intravenous (IV) treatment for 1 to 7 days followed by an oral antibiotic course in achieving full recovery 3 months after presentation. Children will be randomly allocated to the 'entirely oral antibiotic' group or the 'standard treatment' group.

The study will assess families' perspectives and decision-making regarding the duration of oral antibiotic courses prescribed to children (4-17 years) who present with uncomplicated bacterial infections at the Royal Children's Hospital (RCH) Emergency Department (ED). The study will involve (i) children discharged from ED on oral antibiotics and (ii) children transferred to Hospital-in-the-Home (HITH) on IV antibiotics who then switch to oral antibiotics. In addition, the study will assess how feasible and acceptable it is to track children's symptoms via the Garmin Smartwatch and the WeGuide platform (WeGuide is a patient engagement software platform that allows for enrolment, consent, and data collection \[via questionnaires/surveys and from the Garmin Smartwatches\] through a singular platform).