Clinical trial NCT03052088: Diagnostic Accuracy of a Host-response Based Diagnostic Tool for Distinguishing Between Bacterial and Viral Etiologies in Pediatric Patients
Official title: 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)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Fever
Respiratory Tract Infections
Lead sponsor: MeMed Diagnostics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: European Commission
name: Heidelberg University
name: University of Parma
First posted: 2017-02-14
Enrollment: 1140
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 0-7 days after the initiation of symptoms
Secondary outcomes:
measure: 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
timeFrame: 0-7 days after the initiation of symptoms
measure: To compare ImmunoXpert™ results with the physician suspected diagnosis at time of patient recruitment and compared to the reference standard diagnosis
timeFrame: 0-7 days after the initiation of symptoms
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Kinderklinik Universitatsmedizin Mannheim
city: Parma
country: Italy
facility: Pietro Barilla Children's Hospital
Study officials:
affiliation: Kinderklinik Universitatsmedizine mannheim
name: Tobias Tenenbaum, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.