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

NCT ID: NCT06426147

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 2200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-08
• Study Completion Date: 2027-08-01

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. 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

L-citrulline

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

Group Type: EXPERIMENTAL

L-citrulline

Intervention Type: DIETARY_SUPPLEMENT

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

L-citrulline

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

Intervention Type: DIETARY_SUPPLEMENT

Placebo

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

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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 makes it unlikely that the participant would complete the follow up until day 28 of study.

• Minimum Eligible Age: 0 Months
• Maximum Eligible Age: 60 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Barcelona Institute for Global Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Quique Bassat, Prof

Role: PRINCIPAL_INVESTIGATOR

Barcelona Institute for Global Health

Locations

Hararghe Health Research

Harar, , Ethiopia

Site Status: NOT_YET_RECRUITING

Hospital Central de Maputo

Maputo, , Mozambique

Site Status: RECRUITING

Countries

Ethiopia; Mozambique

Central Contacts

Quique Bassat, Prof

Role: CONTACT

quique.bassat@isglobal.org

93 227 92 12

Barbara Baro, PhD

Role: CONTACT

barbara.baro@isglobal.org

93 227 92 12

Facility Contacts

Lola Madrid

Role: primary

Lola.Madrid-Castillo@lshtm.ac.uk

Chris Buck

Role: primary

WBuck@mednet.ucla.edu

Other Identifiers

EChiLiBRiST CT2

Identifier Type: -

Identifier Source: org_study_id