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

Completed

• Conditions: Fever; Infectious Disease; Viremia

• Registration Number: NCT03224026
• Lead Sponsor: MeMed Diagnostics Ltd.

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2017-07-17
• Study First Submitted QC: 2017-07-18
• Study First Posted: 2017-07-21
• Primary Completion: 2018-06
• Study Completion: 2018-08
• Status Verified: 2022-12
• Last Update Submitted: 2023-01-03
• Last Update Posted: 2023-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 206

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Diagnostic accuracy compared to expert panel for bacterial versus viral.	0-7 days after initiation of symptoms	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 γ-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)

Secondary Outcome Measures

Name	Time	Method
Comparison of biomarker levels in patients with different etiologies as classified by the expert panel or healthy.	0-7 days after initiation of symptoms in cases with infection.	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: 1. The proteomic signature is a combination of different markers including: tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL), interferon γ-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).; 2. 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).; 3. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL).; 4. interferon γ-induced protein-10 (IP-10) (pg/mL).; 5. C-reactive protein (CRP) (mg/L).
Prevalence of viruses in children with fever without source.	0-7 days after the initiation of symptoms	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.
Diagnostic accuracy compared to microbiology gold standard for ruling out invasive bacterial infection.	0-7 days after initiation of symptoms	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 γ-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).

Trial Locations

Locations (1)

Geneva University Hospitals; 🇨🇭 Geneva, Switzerland