Diagnostic Accuracy of a Host-response Based Diagnostic Tool for Distinguishing Between Bacterial and Viral Etiologies in Pediatric Patients (AutoPilot)

A Multi-center, Prospective, Pilot Study to Validate the Diagnostic Accuracy and Assess the Potential Clinical Utility of a Host-response Based Diagnostic Tool for Distinguishing Between Bacterial and Viral Etiologies in Pediatric Patients Presenting to the Emergency Department With Respiratory Tract Infection (RTI) or Fever Without Source (FWS)

This is a prospective clinical validation study of a novel regulatory approved (CE-IVD) diagnostic assay called ImmunoXpert™ that will enroll 1222 pediatric patients. The study aims to externally validate the tool's diagnostic accuracy and estimate the potential improvement in health and economic outcomes following the usage of ImmunoXpert™. Additionally, statistical analysis will be performed to compare ImmunoXpert™ accuracy to current practice lab testing (e.g. WBC, CRP, and PCT) and clinical suspicion at time of requisition. Enrolled patients will be managed according to the current standard of care and per standard institutional procedures.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Fever

• Study Type: Observational
• Enrollment (Actual): 1140

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany, 68167
    • Kinderklinik Universitatsmedizin Mannheim
• Italy
  • Parma, Italy, 43126
    • Pietro Barilla Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Eligible subjects from both genders that present to the ED due to suspected RTI, or FWS. Each of these patients falls into one of the following categories:

1. Patients with an acute bacterial infection
2. Patients with an acute viral infection
3. Patients with an acute co-infection (bacterial and viral)
4. Patients with an undetermined disease etiology

Description

Inclusion Criteria:

• Legal guardian signs an informed consent
• Documented peak temperature ≥ 38°C (100.4°F)
• Symptom duration ≤ 7 days
• Clinical suspicion of RTI (OR) fever without a clear source after clinical examination

Exclusion Criteria:

• Another episode of febrile infection within the past 2 weeks
• Antibiotic treatment of over 48 hours
• Congenital immune deficiency (CID)
• A proven or suspected HIV, HBV, HCV infection
• Active malignancy
• Current treatment with immune-suppressive or immune-modulating therapies, including without limitations:
• Use of high dose steroids >1 mg/kg/day prednisone or equivalent in the past two weeks
• Monoclonal antibodies, anti-TNF agents
• Intravenous immunoglobulin (IVIG)
• Cyclosporine, Cyclophosphamide, Tacrolimus
• G/GM-CSF, Interferons
• Other severe illnesses that affect life expectancy and/or quality of life such as:
• Severe psychomotor retardation
• Post-transplant patients
• Severe congential metabolic disorder

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To validate the diagnostic accuracy and assess the clinical utility of a host-response based diagnostic tool, for differentiating between bacterial and viral etiologies in pediatric patients >90 days old with suspicion of RTI or FWS	0-7 days after the initiation of symptoms

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the diagnostic accuracy of a host-response based diagnostic to currently available lab measures (WBC, ANC, CRP and PCT), using sensitivity and specificity measures and predetermined cutoffs	0-7 days after the initiation of symptoms
To compare ImmunoXpert™ results with the physician suspected diagnosis at time of patient recruitment and compared to the reference standard diagnosis	0-7 days after the initiation of symptoms

Collaborators and Investigators

• Sponsor: MeMed Diagnostics Ltd.
• Collaborators: Heidelberg University; European Commission; University of Parma
• Investigators: Principal Investigator: Tobias Tenenbaum, MD, Kinderklinik Universitatsmedizine mannheim

Publications and helpful links

General Publications

• Oved K, Cohen A, Boico O, Navon R, Friedman T, Etshtein L, Kriger O, Bamberger E, Fonar Y, Yacobov R, Wolchinsky R, Denkberg G, Dotan Y, Hochberg A, Reiter Y, Grupper M, Srugo I, Feigin P, Gorfine M, Chistyakov I, Dagan R, Klein A, Potasman I, Eden E. A novel host-proteome signature for distinguishing between acute bacterial and viral infections. PLoS One. 2015 Mar 18;10(3):e0120012. doi: 10.1371/journal.pone.0120012. eCollection 2015.
• van Houten CB, de Groot JAH, Klein A, Srugo I, Chistyakov I, de Waal W, Meijssen CB, Avis W, Wolfs TFW, Shachor-Meyouhas Y, Stein M, Sanders EAM, Bont LJ. A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study. Lancet Infect Dis. 2017 Apr;17(4):431-440. doi: 10.1016/S1473-3099(16)30519-9. Epub 2016 Dec 22.
• Eden E, Srugo I, Gottlieb T, Navon R, Boico O, Cohen A, Bamberger E, Klein A, Oved K. Diagnostic accuracy of a TRAIL, IP-10 and CRP combination for discriminating bacterial and viral etiologies at the Emergency Department. J Infect. 2016 Aug;73(2):177-80. doi: 10.1016/j.jinf.2016.05.002. Epub 2016 May 30. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2017
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: February 10, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Body Temperature Changes; Infections; Fever; Respiratory Tract Infections
• Other Study ID Numbers: MM-1006-AP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No