The use of invasive life support in patients with a prolonged critical illness clearly saves lives but carries substantial risks, including intensive care unit-acquired weakness (ICUAW) and long-term disability. Early mobilisation might improve outcomes, yet the evidence is conflicting and complicated by the lack of a responsive outcome measurement to detect change in critically ill patients’ physical function and activity. The Chelsea Critical Care Physical Assessment tool (CPAx) is a valid and reliable instrument for patients at risk of ICUAW. However, its ability to measure change over time (responsiveness) and the minimal clinically important difference (MCID) have not yet been rigorously investigated.
The primary objective of this prospective, international, multicentre, longitudinal cohort study is to investigate responsiveness and to establish the MCID of the CPAx during the ‘intensive care unit (ICU) period’, from ICU baseline to ICU discharge, and ‘hospital period’, from ICU to hospital discharge. Adults with any critical illness who are mechanically ventilated for at least 72 hours, expected to remain in ICU (≥48 hours) and being treated by a physiotherapist are eligible for study inclusion. Functional measurements, including the CPAx and a global rating of change (GRC) scale, will be collected during routine physiotherapy. Responsiveness will be evaluated primarily using the GRC as an anchor to distinguish changed from unchanged/deteriorated patients (criterion validity). As such, the magnitude of change will be analysed with receiver operating characteristics. Additionally, construct validity will be explored with correlation coefficients and effect sizes to confirm/reject a priori formulated hypotheses. MCID will be investigated with anchor-based and distribution-based methods. We plan to recruit 120 patients across three sites in Australia and Switzerland.
Ethical approval has been obtained from each local ethics committee (Canton of Bern, Switzerland (2024-00346), Monash Health, Australia (HREC/106143/MonH-2024-438474(v3)), the Alfred, Australia (490/24)). The results will be disseminated through international/national conferences, peer-reviewed journals and social media. The high quality, rigorous testing of the CPAx could benefit researchers, clinicians and patients.
Severe intraventricular haemorrhage (IVH) and white matter injury (WMI) are major neurological complications in preterm infants, leading to long-term neurodevelopmental impairments. Despite advances in neonatal care, effective treatments are lacking. Umbilical cord blood cell (UCBC) therapy shows neuroprotective potential, with autologous sources ideal but often not feasible due to the unpredictability of preterm births. Allogeneic UCBCs offer an alternative, although immunogenicity and human leucocyte antigen (HLA) compatibility present challenges with knowledge gaps in their relevance in neonatal populations. This study aims to assess the feasibility and safety of partially HLA-matched allogeneic UCBC therapy in preterm infants with severe brain injury.
The ALLO trial is an open-label, phase I, single-arm feasibility and safety study conducted at Monash Children’s Hospital, Victoria, Australia. Preterm infants born before 28 weeks (ALLO-1) or between 28 weeks and 36+6 weeks (ALLO-2) gestational age with severe brain injury identified on neuroimaging will be enrolled. Severe brain injury is defined as grade 3 or 4 IVH or significant WMI. Exclusion criteria include major congenital anomalies or redirection to comfort care. Eligible infants will receive a single intravenous infusion of unrelated, allogeneic, partially HLA-matched (4/6 or 5/6 HLA match) UCBCs sourced from a public cord blood bank. The target dose is 50 million total nucleated cells per kilogram body weight. Infusion will occur within 2–3 weeks of confirmation of eligibility, contingent on clinical stability and absence of active sepsis. Primary outcome includes: (1) feasibility, defined as having more than 60% of enrolled infants with an eligible allogeneic partially matched cord blood unit available and (2) safety, defined as absence of severe adverse events within 48 hours of infusion or graft-versus-host disease within 3 months of infusion. Secondary outcomes include survival, neonatal morbidities, neurodevelopmental assessments and serum cytokine analysis.
Monash HREC has granted full ethics approval (RES-23-0000-297A) for the study, including the research use of allogeneic cord blood from compassionate donations by healthy donors, facilitated through the Bone Marrow Donor Institute Cord Blood Bank within the AusCord network. Findings will be disseminated through peer-reviewed publications and conference presentations, contributing to the development of novel neuroreparative therapies for preterm brain injury.
ACTRN12623001352695 (The Australian New Zealand Clinical Trials Registry).