Infectious DiseaseNCT06426147
L-citrulline to Improve Adverse Outcomes in Admitted Children (EChiLiBRiST, Clinical Trial 2, Inpatients)
A study testing L-citrulline in people with Infectious Disease and Infections, run by Barcelona Institute for Global Health at 2 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 0 to 60 months
- Conditions the study is for
- Infectious Disease, Infections, Child, Only
- What is being tested?
- L-citrulline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,200 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 8 Dec 2025to 1 Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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 makes it unlikely that the participant would complete the follow up until day 28 of study.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Ethiopia1 site, 1 recruiting
- Recruiting
Hararghe Health Research
Harar
Lola Madrid, Lola.Madrid-Castillo@lshtm.ac.uk
Mozambique1 site, 1 recruiting
- Recruiting
Hospital Central de Maputo
Maputo
Chris Buck, WBuck@mednet.ucla.edu
About this study
Official title: A Randomised, Double-blind, Placebo-controlled Trial of L-Citrulline Oral Supplementation to Improve Short and Long-term Outcomes of Admitted Febrile Paediatric Patients With Biomarker-determined High-risk of Adverse Outcomes
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:
- 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
- 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.
Read the detailed description
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.
- Conditions
- Infectious Disease, Infections, Child, Only
- Being tested
- L-citrulline, Placebo
- Medical subject headings
- Communicable Diseases, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDietary supplement
1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days
PlaceboDietary supplement
1 or 2 sachets every 12 hours (depending on weight-band) for 28 days
| Study group | Role | What they receive |
|---|---|---|
| L-citrulline | Experimental | 1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days Receives: Dietary Supplement: L-citrulline |
| Placebo | Placebo comparator | 1 or 2 sachets every 12 hours (depending on weight-band) for 28 days Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to day 28
Secondary outcomes (18)
Mortality
Proportion of participants with mortality between day 0 and day 28 after recruitment and/or up to hospital discharge.
Measured: 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.
Measured: 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)
Measured: Up to day 28
Need for organ support
Proportion of participants with need for organ support
Measured: Up to day 28
Clinical shock
Proportion of participants with clinical shock
Measured: Up to day 28
Severe respiratory distress
Proportion of participants with severe respiratory distress
Measured: Up to day 28
Coma
Proportion of participants with coma
Measured: 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)
Measured: Up to day 28
Median duration of antibiotic treatment
Median duration of antibiotic treatment up to day 28
Measured: Up to day 28
Oxygen requirement
Proportion of participants with oxygen requirement up to D28 and/or up to hospital discharge
Measured: 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
Measured: 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
Measured: Up to day 28
Lenght of hospitalisation
Length of hospitalisation up to D28 and/or up to hospital discharge
Measured: Up to day 28
Mortality
Proportion of participants with mortality up to M6
Measured: Up to month 6
Secondary consultation or hospitalisations
Proportion of participants with secondary consultations or hospitalisations up to M6
Measured: Up to month 6
Proportion of participants with serious adverse events
Proportion of participants with serious adverse events up to month 6
Measured: 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.
Measured: Up to month 6
Proportion of participants with adverse events
Proportion of participants with adverse events up to D30.
Measured: Up to day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2024
- Study start8 Dec 2025
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infectious DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Barcelona Institute for Global Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Quique Bassat, Prof, Principal investigator, Barcelona Institute for Global Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06426147
- Sponsor's protocol ID
- EChiLiBRiST CT2
- Status last verified
- Feb 2026
- First submitted
- 10 May 2024
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled Trial of L-Citrulline Oral Supplementation to Improve Short and Long-term Outcomes of Admitted Febrile Paediatric Patients With Biomarker-determined High-risk of Adverse Outcomes
- ClinicalTrials.gov ID
- NCT06426147
- Acronym / sponsor ID
- EChiLiBRiST CT2
- Conditions
- Infectious Disease, Infections, Child, Only
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,200 participants (estimated)
- Lead sponsor
- Barcelona Institute for Global HealthUniversity, hospital or other
- Study start
- 8 Dec 2025 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Aug 2027 (estimated)
- First posted
- 23 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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
- 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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-citrulline | Experimental | Dietary Supplement: L-citrulline1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days |
| Placebo | Placebo comparator | Dietary Supplement: Placebo1 or 2 sachets every 12 hours (depending on weight-band) for 28 days |
Who may qualify
- Ages
- 0 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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 .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-citrulline1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days | Dietary supplement | L-citrulline |
| Placebo1 or 2 sachets every 12 hours (depending on weight-band) for 28 days | Dietary supplement | Placebo |
Primary outcome
Adverse disease outcome
Time frame: Up to day 28
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)
18 secondary outcomes
Mortality
Time frame: Up to day 28
Incident neurological sequelae
Time frame: Up to day 28
Major adverse kidney event
Time frame: Up to day 28
Need for organ support
Time frame: Up to day 28
Clinical shock
Time frame: Up to day 28
Severe respiratory distress
Time frame: Up to day 28
Coma
Time frame: Up to day 28
Need for readmission
Time frame: Up to day 28
Median duration of antibiotic treatment
Time frame: Up to day 28
Oxygen requirement
Time frame: Up to day 28
Radiological pneumonia
Time frame: Up to day 28
Hypoxemia (Sp02 <90%)
Time frame: Up to day 28
Lenght of hospitalisation
Time frame: Up to day 28
Mortality
Time frame: Up to month 6
Secondary consultation or hospitalisations
Time frame: Up to month 6
Proportion of participants with serious adverse events
Time frame: Up to month 6
Proportion of participants with suspected unexpected serious adverse reactions
Time frame: Up to month 6
Proportion of participants with adverse events
Time frame: Up to day 30
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Quique Bassat, Prof principal investigator
Barcelona Institute for Global Health
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-citrulline in people with Infectious Disease and Infections, run by Barcelona Institute for Global Health at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Ethiopia, Mozambique. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Quique Bassat, Prof (93 227 92 12, quique.bassat@isglobal.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse disease outcome (time frame: Up to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.