In low and middle-income countries, children admitted to hospital are not similarly ill, and do not all have a comparable prognosis. In fact, understanding at first encounter their risk of developing adverse outcomes (including mortality) could allow a more focused management and the tailoring of specific interventions to decrease in hospital mortality, and post discharge adverse longer-term outcomes. This clinical trial, part of the EChiLiBRiST larger project ("Development and validation of a quantitative point-of-care test for the measurement of severity biomarkers to improve risk stratification of fever syndromes and enhance child survival") has the two-fold objective of:
1. Assessing whether a POINT-OF-CARE rapid triaging test (PoC RTT) based on the quantitative measurement at the bedside of the "prognostic" biomarker sTREM-1 (soluble-triggering receptor expressed on myeloid cells 1) can reliably identify those admitted children with a higher risk of adverse outcomes; and
2. Assessing whether the therapeutic intervention (the L-arginine precursor, L-Citrulline, key in the nitric oxide biosynthesis), administered orally for 28 days to those children aged 1-\<60 months identified as "moderate-to-high risk" by the prognostic biomarker can improve outcomes as compared to those receiving an indistinguishable placebo.
This second objective will be assessed in a prospective multi-country, multi-site, individually randomised, two-arm, placebo-controlled, double blind clinical trial involving \~888 children 1-\<60m of age admitted to hospital and determined to be at high risk of adverse outcomes by their baseline sTREM-1 levels. The trial will compare the efficacy of a twice-daily dose of L-citrulline syrup vs placebo (200-300mg/kg/day depending on weight-band; for 28 days) in reducing adverse outcomes in children with severe disease. The trial will be running independently but in parallel in two high-mortality settings in Mozambique and in Ethiopia.
Who can participate
Age range
0 Months – 60 Months
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Enrolled in the initial prognostic screening component.
* Sick children with fever (axillary temperature\>37.5ºC) or a history of fever (within the preceding 72h) or with suspected severe disease.
* 1m-\<60 months of age.
* With an indication for admission, or having already been admitted to hospital due to their illness.
* With an sTREM-1 PoC result classifying their disease as of "moderate-high risk" ("yellow" or "red") upon study recruitment and within D3.
* Residents in the study area or willing to be contacted and traced during the study duration.
* Willing to sign an informed consent document.
* Willing to undergo and adhere to study procedures as explained in the IC document.
Exclusion Criteria:
* Admission to hospital for social reasons (and not on account of their disease).
* Children for which informed consent document has not been signed.
* Known allergy or contraindication to any of the study supplements including lactose intolerance or observing a lactose-free diet.
* Concurrent participation in any other clinical trial.
* Patient under NPO or "nothing by mouth" prescription .
* Contraindication for the insertion of a nasogastric tube (NGT) of for the enteral administration of drugs through the NGT in children who cannot tolerate by mouth.
* Critically sick patient whose prognosis is considered by the clinical researcher as fatal outcome in the following hours after screening.
* Any other condition determined by the investigators that mak…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.