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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,200
- 试验地点
- 2
- 主要终点
- Adverse disease outcome
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 0 Months 至 60 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 D
- •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.
排除标准
- •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.
研究组 & 干预措施
L-citrulline
1 or 2 sachets every 12 hours (200-300mg/kg/day depending on weight-band) for 28 days
干预措施: L-citrulline (Dietary Supplement)
Placebo
1 or 2 sachets every 12 hours (depending on weight-band) for 28 days
干预措施: Placebo (Dietary Supplement)
结局指标
主要结局
Adverse disease outcome
时间窗: 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)
次要结局
- Mortality(Up to month 6)
- Major adverse kidney event(Up to day 28)
- Clinical shock(Up to day 28)
- Severe respiratory distress(Up to day 28)
- Lenght of hospitalisation(Up to day 28)
- Coma(Up to day 28)
- Median duration of antibiotic treatment(Up to day 28)
- Radiological pneumonia(Up to day 28)
- Incident neurological sequelae(Up to day 28)
- Need for organ support(Up to day 28)
- Need for readmission(Up to day 28)
- Hypoxemia (Sp02 <90%)(Up to day 28)
- Secondary consultation or hospitalisations(Up to month 6)
- Proportion of participants with suspected unexpected serious adverse reactions(Up to month 6)
- Proportion of participants with adverse events(Up to day 30)
- Oxygen requirement(Up to day 28)
- Proportion of participants with serious adverse events(Up to month 6)
- Mortality(Up to day 28)