An interventional study of L-citrulline and Placebo in Infectious Disease, Infections and Child, Only, sponsored by Barcelona Institute for Global Health. Recruiting at 2 sites in 2 countries. Open to participants aged 0 Months to 60 Months. Per ClinicalTrials.gov, last updated 2026-02-23.
Sponsored by Barcelona Institute for Global Health · Not applicable, Interventional, and Treatment
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:
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.
Children admitted to hospital and meeting the study eligibility criteria who are 0-\<60 months of age will be eligible for study inclusion, and for initial biomarker screening using the study-designed rapid triaging PoC test, based on the measurement of sTREM-1. Study participants aged 1m-\<5 years of age with sTREM-1 values classified as moderate (i.e., "yellow") or high-risk (i.e., "red") in the traffic light risk-stratification system will be randomly allocated (1:1) to receive L-Cit intervention or placebo. All study participants will be followed for 6 months, with study visits at the study hospitals or at home or via phone communication after discharge at day 3, day 5, day 7, day 28, and month 6. The study primary outcome will be "adverse disease outcome", defined as a composite of mortality, incident neurological sequelae, major adverse kidney event at discharge, need for organ support, clinical shock, coma, severe respiratory distress or need for readmission within 28 days after recruitment.
626 studies on the registry are indexed under Communicable Diseases; 128 are open to participants now.
This study's planned enrollment of 2,200 is above the median of 89 across 380 interventional studies indexed under Communicable Diseases.
Browse Communicable Diseases studies →Barcelona Institute for Global Health is the lead sponsor of 24 studies on the registry; 5 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days
Dietary Supplement: L-citrulline
1 or 2 sachets every 12 hours (depending on weight-band) for 28 days
Dietary Supplement: Placebo
1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days
1 or 2 sachets every 12 hours (depending on weight-band) for 28 days
Adverse disease outcome
Proportion of participants with "adverse disease outcome" defined as a composite of (i.e., the occurrence between D0 and D28 after recruitment of at least one -or more- of the following adverse outcomes): * Mortality * Incident neurological sequelae * Major adverse kidney event at discharge (MAKE-DC, defined as a severe AKI event between 2-7 days or a discharge eGFR\<60mL/min per 1.73m2) * Need for organ support * Clinical shock * Coma * Severe respiratory distress * Need for readmission within the first 28 days post-recruitment (after having been discharged)
Time frame: Up to day 28
Mortality
Proportion of participants with mortality between day 0 and day 28 after recruitment and/or up to hospital discharge.
Time frame: Up to day 28
Incident neurological sequelae
Proportion of participants with incident neurological sequelae between day 0 and day 28 after recruitment and/or up to hospital discharge.
Time frame: Up to day 28
Major adverse kidney event
Proportion of participants with major adverse kidney event at discharge (MAKE-DC, defined as a severe AKI event between 2-7 days or a discharge eGFR\<60mL/min per 1.73m2)
Time frame: Up to day 28
Need for organ support
Proportion of participants with need for organ support
Time frame: Up to day 28
Clinical shock
Proportion of participants with clinical shock
Time frame: Up to day 28
Severe respiratory distress
Proportion of participants with severe respiratory distress
Time frame: Up to day 28
Coma
Proportion of participants with coma
Time frame: Up to day 28
Need for readmission
Proportion of participants with need for readmission within the first 28 days post-recruitment (after having been discharged)
Time frame: Up to day 28
Median duration of antibiotic treatment
Median duration of antibiotic treatment up to day 28
Time frame: Up to day 28
Oxygen requirement
Proportion of participants with oxygen requirement up to D28 and/or up to hospital discharge
Time frame: Up to day 28
Radiological pneumonia
Proportion of participants with radiological pneumonia among children with RTI up to D28 and/or up to hospital discharge
Time frame: Up to day 28
Hypoxemia (Sp02 <90%)
Proportion of participants with hypoxemia (Sat 02\<90% irrespective of supplementary oxygen in absence of cyanotic heart disease) up to D28 and/or up to hospital discharge
Time frame: Up to day 28
Lenght of hospitalisation
Length of hospitalisation up to D28 and/or up to hospital discharge
Time frame: Up to day 28
Mortality
Proportion of participants with mortality up to M6
Time frame: Up to month 6
Secondary consultation or hospitalisations
Proportion of participants with secondary consultations or hospitalisations up to M6
Time frame: Up to month 6
Proportion of participants with serious adverse events
Proportion of participants with serious adverse events up to month 6
Time frame: Up to month 6
Proportion of participants with suspected unexpected serious adverse reactions
Proportion of participants with suspected unexpected serious adverse reactions up to M6.
Time frame: Up to month 6
Proportion of participants with adverse events
Proportion of participants with adverse events up to D30.
Time frame: Up to day 30
Concentration of circulating mediators of host immune and endothelial function, inflammation, intestinal barrier function, and neuronal damage
Concentration of circulating mediators of host immune and endothelial function, inflammation, intestinal barrier function, and neuronal damage at baseline, D3 and D7
Time frame: Up to day 7
Lactate levels
Levels of lactate at baseline and D3
Time frame: Up to day 3
Levels of markers of kidney function
Levels of markers of kidney function (creatinine, urea, saliva urea nitrogen (SUN), uNGAL etc.) at baseline, D3, D7 and at discharge
Time frame: Up to day 7
PoC-RTT prognostic performance
Prognostic performance of PoC-RTT measured sTREM-1 values at baseline among children (0-\<60 months of age) with adverse outcomes up to D28.
Time frame: Up to day 28
Prognostic performance of a larger panel of biomarkers
Prognostic performance of a larger panel of prognostic biomarkers (circulating markers of endothelial function, inflammation, intestinal barrier function, and neuronal damage) at baseline.
Time frame: At baseline
Plan to share: Yes — This clinical trial, as part of the wider EChiLiBRiST project, is committed to EU-funded Horizon 2021 aims to improve and maximize access to and reuse of research data generated by the Project. Biological samples and data will be shared using material and data transfer agreements with the collaborating institutions. The full protocol will be available on request to any interested professional and may be published in peer-reviewed journals or deposited in an online repository. A fully de-identified data set of the complete patient-level data will be available for sharing purposes as soon as the the analysis is completed and no later than five years after the publication of the trial.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: A fully de-identified data set of the complete patient-level data will be available for sharing purposes as soon as the data analysis is completed and no later than five years after the publication of the trial.
Access criteria: On request to any interested professional
No publications or documents are linked to this record.
Started Dec 2025 (actual). Primary completion is estimated for Jun 2027, 17 months after the start.
Of 128 non-industry interventional studies with no phase under Communicable Diseases, half reached primary completion within 21 months of starting (the median), counting those still running; a quarter within 6 and three quarters within 36. This study's planned 17 months is below that.
Counting every sponsor, half of 144 studies reached it within 21 months; a quarter within 6 and three quarters within 36.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Citrulline
Barcelona Institute for Global Health