A Multi-country, Two-arm, Open-label, Superiority, Randomised Controlled Trial to Study the Performance of a Rapid Triage Test Compared to Standard of Care (IMCI-based) to Guide Admission/Discharge Decisions During the First Clinical Assessment of Children With Fever
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 5,212
- Locations
- 3
- Primary Endpoint
- Appropriateness of discharge
Study Overview
Brief Summary
The overall aim of the study is to provide evidence that introducing novel biomarkers evaluation at triaging (first clinical assessment), in combination with IMCI-based guidelines (SoC), is a viable strategy to enhance rapid and accurate identification of febrile children at increased risk of life-threatening infections compared to IMCI-based strategies alone (SoC), and to demonstrate whether this results in enhanced decisions of admission/referral vs discharge, and enhanced overall health outcome of children with acute fever in sub-Saharan Africa.
Detailed Description
This is a multi-country, open label, two-arm, parallel-group, superiority, individually randomised clinical trial involving 2,606 febrile children per country (two countries, total n=5212). The trial will compare the performance of a point-of-care rapid triage test (POC-RTT) based on suPAR levels (i.e.suPARnostic®) (in combination with IMCI-based strategies, which are the SoC) to appropriately support admission/referral vs discharge decisions during the first clinical assessment of febrile children aged 2-<60 months compared to the standard of care based on IMCI guidelines.
Febrile children meeting the study eligibility criteria will be randomly allocated (1:1) to one of the two triaging approaches (arms): 1) IMCI-based standard of care (SoC); or 2) IMCI-enhanced by suPAR levels (SoC + suPAR POC). Blood will be collected from all participants and only those randomised to the intervention arm (arm 2) will have suPAR levels determined at the POC using suPARnostic® device.
At baseline, all children will undergo two clinical assessments. Primary composite endpoint of "appropriateness of discharge" will be based on the first clinical assessment, which is more representative of real-world clinical practice. However, the ultimate decision on admission/referral vs discharge will be based on the second clinical assessment, which will ensure the safest possible clinical practice in the context of a clinical trial.
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At baseline, during the first clinical assessment, all participants will be evaluated following the SoC based on IMCI guidelines, which will guide management decisions, including clinical diagnosis and treatment. This IMCI-guideline based evaluation during this first clinical assessment will be conducted by a health worker as per routine clinical practice in the outpatient departments of each study site.
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In the participants randomised to the control arm, decision of admission/referral vs discharge home will be informed by IMCI-based evaluation alone (SoC).
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In the participants randomised to the intervention arm, decision of admission/referral vs discharge home will be informed by IMCI-based evaluation enhanced by suPAR levels (SoC + suPAR POC). Clinicians will be instructed to admit for further observation any child with suPAR levels equal or superior to 4 ng/mL (except for confirmed malaria, that it will be equal or superior to 6 ng/mL), as these patients are at moderate or high risk of adverse outcomes and death. On the other hand, children with suPAR levels below 4 ng/mL (or below 6 ng/mL in case of confirmed malaria) will be eligible for discharge home at the criteria of the clinician, considering the signs and symptoms found, and based on IMCI guidelines. Hence, should clinicians in charge deem that any of these children still require admission, they will be instructed to continue with the admission regardless of suPAR levels.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 2 Months to 60 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥2 months and <60 months
- •Written informed consent from the child's parent or caregiver
- •History of fever for ≤7 days OR hypothermia (i.e., axillary temperature <35.5ºC) OR suspected severe infection (e.g., in children with moderate or severe acute malnutrition).
- •Lives within the catchment area of the study facility and must intend to continue to reside there for the duration of the study
- •For the RTI sub-study only: presence of respiratory symptoms compatible with RTI.
Exclusion Criteria
- •Weight less than 2.5kg
- •Main reason for consultation is an injury, trauma or acute poisoning
- •Enrolled in another clinical trial testing a new drug
- •Enrolled in a vaccine trial in the last 3 months.
- •Any other condition determined by the investigators that makes it unlikely that the participant would complete the study
Arms & Interventions
IMCI alone
IMCI-guidelines (standard of care)
IMCI-enhanced by suPAR levels (SoC + suPAR POC).
IMCI-guidelines (standard of care) + Point-Of-Care (POC) test based on suPAR quantification
Intervention: IMCI-enhanced by suPAR levels (SoC + suPAR POC) (Other)
Outcomes
Primary Outcomes
Appropriateness of discharge
Time Frame: Up to day 7
The primary outcome is the proportion of "appropriateness of discharge" according to the first clinical assessment of febrile children aged 2-\<60 months compared among the 2 study arms. Inappropriate discharge is defined as a composite of (fulfilling at least one of the following): 1. Presence at baseline of World Health Organization (WHO)-proposed danger signs in discharged children; OR 2. Presence of WHO-proposed danger signs on day 3 post-discharge; OR 3. Requirement for additional visit at the health facility or admission at day 7; OR 4. Death on day 7 post-discharge. The absence of any of these endpoints will be considered an appropriate discharge.
Secondary Outcomes
- Referrals to higher level facilities(Up to day 28)
- Severe disease(Up to day 7)
- Mortality(Up to day 28)
- Secondary consultations or admissions(Up to day 28)
- Symptoms duration(Up to day 28)
- Hospital stay length(Up to day 28)
- Serious adverse events(Up to day 28)
- Discharge in the major aetiological diagnosis(Up to Day 28)
- Biomarkers in admitted(Up to Day 28)
- Biomarkers reduction of outcomes(Up to Day 28)
- Admissions in the routine care(Up to Day 28)
- Severe disease(Up to day 7)
- Symptoms duration(Up to day 28)
- Hospital stay length(Up to day 28)
- Serious adverse events(Up to day 28)