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

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.

Conditions

• Infectious Disease
• Infections
• Child, Only

Interventions

DIETARY_SUPPLEMENT

L-citrulline

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

DIETARY_SUPPLEMENT

Placebo

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

Sponsors & Collaborators

• Barcelona Institute for Global Health

  lead OTHER

Principal Investigators

• Quique Bassat, Prof · Barcelona Institute for Global Health

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

0 Months

Max Age

60 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-12-08

Primary Completion

2027-06-01

Completion

2027-08-01

Countries

• Ethiopia
• Mozambique

Study Locations