A Multi-country, Two-arm, Open-label, Superiority, Randomised Controlled Trial to Study the Performance of a Rapid Triage Test Compared to Standard of Care (IMCI-based) to Guide Admission/Discharge Decisions During the First Clinical Assessment of Children With Fever

This is a multi-country, open label, two-arm, parallel-group, superiority, individually randomised clinical trial involving 2,606 febrile children per country (two countries, total n=5212). The trial will compare the performance of a point-of-care rapid triage test (POC-RTT) based on suPAR levels (i.e.suPARnostic®) (in combination with IMCI-based strategies, which are the SoC) to appropriately support admission/referral vs discharge decisions during the first clinical assessment of febrile children aged 2-<60 months compared to the standard of care based on IMCI guidelines.

Febrile children meeting the study eligibility criteria will be randomly allocated (1:1) to one of the two triaging approaches (arms): 1) IMCI-based standard of care (SoC); or 2) IMCI-enhanced by suPAR levels (SoC + suPAR POC). Blood will be collected from all participants and only those randomised to the intervention arm (arm 2) will have suPAR levels determined at the POC using suPARnostic® device.

At baseline, all children will undergo two clinical assessments. Primary composite endpoint of "appropriateness of discharge" will be based on the first clinical assessment, which is more representative of real-world clinical practice. However, the ultimate decision on admission/referral vs discharge will be based on the second clinical assessment, which will ensure the safest possible clinical practice in the context of a clinical trial.

1. At baseline, during the first clinical assessment, all participants will be evaluated following the SoC based on IMCI guidelines, which will guide management decisions, including clinical diagnosis and treatment. This IMCI-guideline based evaluation during this first clinical assessment will be conducted by a health worker as per routine clinical practice in the outpatient departments of each study site.

2. In the participants randomised to the control arm, decision of admission/referral vs discharge home will be informed by IMCI-based evaluation alone (SoC).

3. In the participants randomised to the intervention arm, decision of admission/referral vs discharge home will be informed by IMCI-based evaluation enhanced by suPAR levels (SoC + suPAR POC). Clinicians will be instructed to admit for further observation any child with suPAR levels equal or superior to 4 ng/mL (except for confirmed malaria, that it will be equal or superior to 6 ng/mL), as these patients are at moderate or high risk of adverse outcomes and death. On the other hand, children with suPAR levels below 4 ng/mL (or below 6 ng/mL in case of confirmed malaria) will be eligible for discharge home at the criteria of the clinician, considering the signs and symptoms found, and based on IMCI guidelines. Hence, should clinicians in charge deem that any of these children still require admission, they will be instructed to continue with the admission regardless of suPAR levels.