Validation of a Proteomic Signature and Assessment of Viremia in Children With Fever Without Source

Fever Clinical Trial

Official title:

Which Virus Leads to Viremia in Children With Fever Without Source and do New Biomarkers Correlate With Viral and Bacterial Infections?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03224026
• Other study ID #: MM-15082-Vir
• Status: Completed
• Start date: November 2015
• Est. completion date: August 2018

Study information

• Verified date: December 2022
• Source: MeMed Diagnostics Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study is an observational blinded Validation study in pediatric patients below 3 years old with a diagnosis of Fever Without Source (FWS). In this study the investigators aim to validate the performance of a proteomic signature aiding the physicians to discriminate between viral and bacterial infections in febrile children. The study will also assess the prevalence of Human Enteroviruses (HEV), Human Parechoviruses (HPeV), Adenovirus (AdV) and Human Herpesvirus type 6 (HHV-6) viremia, as well as Kingella Kingae bacteremia in the study cohort.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: August 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 3 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of FWS (fever of less than 7 days with no cause determined by the history or the physical exam)

• Age < 3 years old

• Informed consent (IC) given by parent or legal guardian

Exclusion Criteria:

• Unavailable blood

• Comorbidities predisposing to infections such as cancer, primary or secondary immunodeficiency, and iatrogenic immunosuppression

Inclusion Criteria for healthy controls:

• Age < 3 years old

• Informed consent (IC) given by parent or legal guardian

• No suspicion of infectious or inflammatory disease at presentation and during the two weeks before.

Related Conditions & MeSH terms

• Communicable Diseases
• Fever
• Infections
• Infectious Disease
• Viremia

Locations

Country	Name	City	State
Switzerland	Geneva University Hospitals	Geneva

Sponsors (2)

Lead Sponsor	Collaborator
MeMed Diagnostics Ltd.	University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

References & Publications (3)

Ambrosioni J, Bridevaux PO, Wagner G, Mamin A, Kaiser L. Epidemiology of viral respiratory infections in a tertiary care centre in the era of molecular diagnosis, Geneva, Switzerland, 2011-2012. Clin Microbiol Infect. 2014 Sep;20(9):O578-84. doi: 10.1111/1469-0691.12525. Epub 2014 Jan 24. — View Citation

Colvin JM, Muenzer JT, Jaffe DM, Smason A, Deych E, Shannon WD, Arens MQ, Buller RS, Lee WM, Weinstock EJ, Weinstock GM, Storch GA. Detection of viruses in young children with fever without an apparent source. Pediatrics. 2012 Dec;130(6):e1455-62. doi: 10.1542/peds.2012-1391. Epub 2012 Nov 5. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic accuracy compared to expert panel for bacterial versus viral.	Sensitivity, specificity, NPV and PPV were measured for ImmunoXpert and Labscore.; The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon ?-induced protein-10 (IP-10) (pg/mL) and C-reactive protein (CRP) (mg/L). The proteomic signature is expressed as a score (no units. ranges 0-100).; The Labscore is a combination of procalcitonin (ng/mL), C-reactive protein (CRP) (mg/L) and urinary dipstix (positive if presence of leucocyturia or nitrites). The Lab-score is expressed as a score (no units. ranges 0-9)	0-7 days after initiation of symptoms
Secondary	Diagnostic accuracy compared to microbiology gold standard for ruling out invasive bacterial infection.	Case by case comparison between microbiology gold standard and ImmunoXpert and Labscore.; The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon ?-induced protein-10 (IP-10) (pg/mL) and C-reactive protein (CRP) (mg/L). The proteomic signature is expressed as a score (no units, ranges 0-100).; The Labscore is a combination of procalcitonin (ng/mL), C-reactive protein (CRP) (mg/L) and urinary dipstix (positive if presence of leucocyturia or nitrites). The Lab-score is expressed as a score (no units, ranges 0-9).	0-7 days after initiation of symptoms
Secondary	Comparison of biomarker levels in patients with different etiologies as classified by the expert panel or healthy.	An expert panel classified a patient as experiencing a bacterial versus viral infection. In addition healthy patients were requited.; The following biomarkers were examined across the healthy versus bacterial versus viral patients: The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon ?-induced protein-10 (IP-10) (pg/mL) and C-reactive protein (CRP) (mg/L). The proteomic signature is expressed as a score (no units, ranges 0-100).; The Labscore is a combination of procalcitonin (ng/mL), C-reactive protein (CRP) (mg/L) and urinary dipstix (positive if presence of leucocyturia or nitrites). The Lab-score is expressed as a score (no units, ranges 0-9).; Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL).; interferon ?-induced protein-10 (IP-10) (pg/mL).; C-reactive protein (CRP) (mg/L).	0-7 days after initiation of symptoms in cases with infection.
Secondary	Prevalence of viruses in children with fever without source.	Prevalence of Human Enteroviruses, Human Parechoviruses, Adenovirus and Human Herpesvirus type 6 viremia and viremia from other microorganism identified by Next-Generation Sequencing (NGS) (no units) or other techniques, as well as K. kingae bacteremia in children under three years old presenting with fever without source.	0-7 days after the initiation of symptoms