- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04726826
Biomarkers of Mortality and Morbidity in Children Hospitalized With Fever
Predictive Biomarkers of Mortality and Morbidity in Children Hospitalized for Acute Febrile Illness
The objective of this study is to identify clinically informative biomarkers of host defense pathways with potential utility as diagnostic and prognostic tools among children hospitalized with acute febrile illness in a resource-constrained sub-Saharan African setting.
The working hypothesis is that a panel of biomarkers, readily measurable from a peripheral blood sample, may serve as a clinically useful instrument to distinguish between common pediatric causes of fever, predict those children at greatest need of aggressive supportive care and/or adjunctive therapies, and identify those children at greatest risk of mortality. The use of objective and quantitative tools may facilitate the triage and clinical care of febrile children admitted to hospital in the sub-Saharan African context.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
For pediatric patients presenting to Jinja Regional Referral Hospital in whom admission to hospital is deemed necessary by an attending physician, the parent or guardian will be approached for consent to participate in the study. If granted, a small volume (1mL) of blood will be withdrawn for processing and storage. A RDT for malaria and whole blood lactate level will be performed at the bedside. Basic demographic and clinical data will be collected from the case admission record, and patients will be followed during their hospital admission. Possible outcomes will include: death, discharge without disability, discharge with disability, abscondment, and loss to follow-up. The length of stay among survivors will be recorded (excluding patients leaving against medical advice).
Serum samples will be shipped to the collaborating laboratory in Canada for analysis for biomarkers. ELISA-based commercially-available assays for biomarker levels will be used to quantify biomarker levels. In order to measure levels of 13 biomarkers from a plasma sample of 500uL or less, highly co-ordinated procedures with experienced technicians are required to perform the ELISA. Our laboratory in Canada has established protocols, experienced staff able to perform the testing, as well as equipment and reagents allowing the testing to be done efficiently. While it would be desirable to augment Ugandan capacity for biomarker testing, this would require significant investment of time and resources for training and testing, and may not be feasible in the context of this early study. If biomarkers can be identified that have clinical utility, laboratory capacity for ELISA measurement of levels should be developed or a simplified platform (e.g., lateral flow immunochromatographic test) should be developed.
Pneumonia and meningitis will be diagnosed clinically. A combination of tachypnea, respiratory distress (nasal flaring, intercostal and/or subcostal indrawing, or cyanosis) and characteristic findings on chest auscultation (asymmetrical air entry, crackles, dullness to percussion) will be used to make a clinical diagnosis of pneumonia. In our setting, chest x-ray is not available on site and radiographic confirmation will not be routinely available. Neck stiffness, positive Kernig's or Brudzinsky's signs, convulsions and coma will be used to make a diagnosis of meningitis. Where a lumbar puncture is performed, according to clinical judgment, the results will be used to complement clinical diagnosis. CSF pleiocytosis or a positive CSF culture for recognized pathogens will be used to support the diagnosis of meningitis.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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-
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Jinja, Uganda
- Jinja Regional Referral Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
The choice of the age range for this study is as follows. Children under 5 represent a vulnerable group, in whom infectious diseases play a major role as contributors to overall mortality. Children under 2 months of age (the neonatal group) represent a unique population with different infectious risks and are therefore outside the scope of our current study.
The reason for exclusion of isolated diarrheal illness is that dehydration, acidosis and electrolyte imbalances are the proximal causes of mortality, rather than activation of host defense pathways with excessive inflammation and endothelial activation. Host biomarkers are therefore not expected to predict mortality with the same accuracy in diarrhea syndromes.
Description
Inclusion Criteria:
- Age 2 months to 5 years
- History of fever within past 48 hours or axillary temperature >37.5°C
- Hospital admission warranted based on clinician judgment
- Consent to blood sampling and data collection
Exclusion Criteria:
- Outside eligible age range
- No history or objective evidence of fever
- Diarrheal illness without other symptoms
- Outpatient management
- Denial of consent to participate in study
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality
Time Frame: through study completion, an average of 1 week
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in-hospital mortality
|
through study completion, an average of 1 week
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hospital length of stay
Time Frame: through study completion, an average of 1 week
|
time from admission to discharge
|
through study completion, an average of 1 week
|
Lambarene organ dysfunction score (LODS), a composite clinical severity score
Time Frame: evaluated at admission
|
clinical severity score
|
evaluated at admission
|
Signs of Inflammation in Children that Kill (SICK), a composite clinical severity score
Time Frame: evaluated at admission
|
clinical severity score
|
evaluated at admission
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael T Hawkes, MD, PhD, University of Alberta
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00106489
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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