Validation of Promising Biomarker Assays to Assess Their Diagnostic Performance Characteristics

Completed

• Conditions: Acute Febrile Illnesses
• Interventions: Diagnostic Test: Biomarker assay

• Registration Number: NCT03047642
• Lead Sponsor: Foundation for Innovative New Diagnostics, Switzerland

Brief Summary

This project aims to evaluate the performance characteristics of rapid tests to differentiate bacterial from non-bacterial infection in febrile adults and children presenting at OPDs (outpatient departments) i.e.("fever triage assays") in three LMICs. The evaluation will include a different commercial biomarker combinations as well as individual biomarkers to assess their individual or combined value in the target population. Markers will be evaluated onsite in ELISA or RDT format, as appropriate. Further, this study aims to contribute to a centralized biobank of well-characterized specimens for use by IVD companies and academic institutions for the development and evaluation of emerging assays.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-10
• Study First Submitted QC: 2017-02-06
• Study First Posted: 2017-02-09
• Study Start: 2017-04-27
• Primary Completion: 2018-10-27
• Study Completion: 2019-11-27
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-15
• Last Update Posted: 2021-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Any non-severely ill subject presenting with acute fever defined as: temperature of more than 38°C at initial evaluation of less than 7 days of symptoms at presentation.

Inclusion criteria:

• Children 2-17 years of age
• Adults 18-65 years of age
• Signed written informed consent for study participation. For recruitment purposes, subjects will be classified into two groups, children and adults. For children, age >2 years is the minimum cut-off, based on the amount of blood volume to be obtained in the study. WHO guidelines for allowable blood volume in 24 hours recommend that no more than 1-5% of total blood volume (75-80 ml/kg for older children) be obtained. Applying the average weight of a 2 year old toddler =12 kg, the allowable blood volume to be drawn in 24 hours at 1-5% of the total blood volume is 9.6 - 48 mL .

For minors, caregivers will provide informed consent. Documented assent for children of 12 to 16 years of age will be required for their participation.

Exclusion Criteria

• Subjects who are felt to be in critical condition (based on clinician assessment or the presence of any general signs of critical illness as defined by WHO guidelines (for children: extensive vomiting, active seizure or recent history of seizures, altered mentation, inability to feed, or any of the severe IMNCI classifications; for adults: impending airway obstruction, central cyanosis, severe respiratory distress, feeble pulse, active seizure or recent history of seizures, or unconsciousness) because the target population for the study is non-severe febrile subjects.
• Subjects can only be enrolled once into the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Brazil febrile patients	Biomarker assay	Children and adults with fever presenting at the outpatient department
Malawi febrile patients	Biomarker assay	Children and adults with fever presenting at the outpatient department
Gabon febrile patients	Biomarker assay	Children with fever or with a recent history of fever presenting at the outpatient department

Primary Outcome Measures

Name	Time	Method
Diagnostic sensitivity and specificity to determine bacterial infections compared to clinical and microbiological results aggregated in a study database.	1year	Microbiological testing (blood culture positive/negative, malaria pos/neg, S. Tyhpi RDT pos/neg) and clinical assessments of symptoms (respiratory, gastro, no foci) will be recorded and reviewed by a clinical panel upon completion of the study to assign a final category (bacterial or non-bacterial). These categories are used in the evaluation of the biomarker assays to evaluate their performance in differentiating bacterial from non-bacterial infections. Where applicable, the same categories will be used to determine the area under the curve by employing receiver operator characteristics (ROC) analysis of quantitative markers.

Trial Locations

Locations (3)

Karonga Prevention Study; 🇲🇼 Chilumba, Karonga District, Malawi

Instituto Nacional de Infectologia Evandro Chagas - Fiocruz (INIEC); 🇧🇷 Rio de Janeiro, Brazil

CERMEL; 🇬🇦 Lambaréné, Gabon