Biomarkers of Mortality and Morbidity in Children Hospitalized With Fever

Fever Clinical Trial

Official title:

Predictive Biomarkers of Mortality and Morbidity in Children Hospitalized for Acute Febrile Illness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04726826
• Other study ID #: Pro00106489
• Status: Completed
• Start date: February 1, 2012
• Est. completion date: September 15, 2013

Study information

• Verified date: January 2021
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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 If granted, a small volume (1mL) of blood will be withdrawn for processing and storage.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2500
• Est. completion date: September 15, 2013
• Est. primary completion date: September 15, 2013
• Gender: All
• Age group: 2 Months to 5 Years

Eligibility

Inclusion Criteria:

1. Age 2 months to 5 years

2. History of fever within past 48 hours or axillary temperature >37.5°C

3. Hospital admission warranted based on clinician judgment

4. Consent to blood sampling and data collection

Exclusion Criteria:

1. Outside eligible age range

2. No history or objective evidence of fever

3. Diarrheal illness without other symptoms

4. Outpatient management

5. Denial of consent to participate in study

Related Conditions & MeSH terms

• Fever

Intervention

Diagnostic Test:
• Diagnostic and prognostic biomarkers
Observational study of biomarkers predictive of morbidity and mortality in febrile children

Locations

Country	Name	City	State
Uganda	Jinja Regional Referral Hospital	Jinja

Sponsors (3)

Lead Sponsor	Collaborator
University of Alberta	Global Health Uganda LTD, University of Toronto

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	in-hospital mortality	through study completion, an average of 1 week
Secondary	Hospital length of stay	time from admission to discharge	through study completion, an average of 1 week
Secondary	Lambarene organ dysfunction score (LODS), a composite clinical severity score	clinical severity score	evaluated at admission
Secondary	Signs of Inflammation in Children that Kill (SICK), a composite clinical severity score	clinical severity score	evaluated at admission