L-citrulline to Improve Adverse Outcomes in Admitted Children (EChiLiBRiST, Clinical Trial 2, Inpatients)

NCT06426147 | Recruiting DMC

• 1 other identifier: EChiLiBRiST CT2
• Study Type: interventional
• Target: 2,200
• Locations: 2 countries
• Sites: 2

Brief 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 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. 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. 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.

Conditions

Infectious Disease; Infections; Child, Only

Outcome Measures

Primary Outcomes (1)

• 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)

  Up to day 28

Secondary Outcomes (18)

• Mortality

  Up to day 28

• Incident neurological sequelae

  Up to day 28

• Major adverse kidney event

  Up to day 28

• Need for organ support

  Up to day 28

• Clinical shock

  Up to day 28

Other Outcomes (5)

• Concentration of circulating mediators of host immune and endothelial function, inflammation, intestinal barrier function, and neuronal damage

  Up to day 7

• Lactate levels

  Up to day 3

• Levels of markers of kidney function

  Up to day 7

Study Arms (2)

L-citrulline

EXPERIMENTAL

1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days

Dietary Supplement: L-citrulline

Placebo

PLACEBO COMPARATOR

1 or 2 sachets every 12 hours (depending on weight-band) for 28 days

Dietary Supplement: Placebo

Interventions

L-citrulline DIETARY_SUPPLEMENT

1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days

L-citrulline

Placebo DIETARY_SUPPLEMENT

1 or 2 sachets every 12 hours (depending on weight-band) for 28 days

Placebo

Eligibility Criteria

• Age: 0 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• m-\<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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Barcelona Institute for Global Health: lead

Study Sites (2)

Hararghe Health Research

Harar, Ethiopia

RECRUITING

Hospital Central de Maputo

Maputo, Mozambique

RECRUITING

MeSH Terms

Conditions

Communicable Diseases; Infections

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Quique Bassat, Prof

  Barcelona Institute for Global Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Quique Bassat, Prof

CONTACT

93 227 92 12; quique.bassat@isglobal.org

Barbara Baro, PhD

CONTACT

93 227 92 12; barbara.baro@isglobal.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2024
• First Posted: May 23, 2024
• Study Start: December 8, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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

Locations

ET (1); MO (1)