Improving outcomes from sepsis in children is a WHO Global Health Priority, yet mortality from sepsis remains high, particularly in low- and middle-income countries (LMICs). This database from children with community-acquired childhood sepsis in LMICs and some high-income countries will allow analysis of the burden of disease, including incidence, severity and outcomes. Understanding these aspects of sepsis care is fundamental for the design and conduct of future international interventional trials to improve childhood sepsis outcomes.

This multicountry retrospective observational study will include children up to 18 years of age presenting to emergency departments with suspected sepsis, defined as admission to hospital for treatment with intravenous antibiotics plus (1) a provisional diagnosis of sepsis and/or (2) treatment for suspected sepsis (operationalised as the administration of one or more fluid bolus to treat impaired perfusion or vasoactive infusion). Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length of stay, and mortality censored at hospital discharge or 30 days from enrolment (whichever occurs first).

Central ethics approval was received from the Royal Children’s Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/100648/RCHM-2023). Each international site will be required to obtain local Institutional Research Ethics Board approval. The findings will be disseminated in peer-reviewed journals, at academic conferences and through lay media. A cleaned study database and individual site-level data will be made available to site investigators upon completion of the study.

This study was registered with the Australian and New Zealand Clinical Trials Registry on 23 January 2024 prior to commencement of recruitment (ACTRN12624000052538).

SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.

CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.

The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).

NCT05614349