Infectious DiseaseNCT03224026
Validation of a Proteomic Signature and Assessment of Viremia in Children With Fever Without Source
An observational study of Infectious Disease and Fever, run by MeMed Diagnostics Ltd. at 1 site in Switzerland.
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… Read more about this study
- Who is it for?
- Ages 1 day to 3 yearsHealthy volunteers can take part
- Conditions the study is for
- Infectious Disease, Fever, Viremia
- How many people
- 206 participants
- Where
- 1 siteSwitzerland
- Study dates
- Nov 2015to Aug 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 3 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Pediatric patients below three years old which were presented with a diagnosis of fever without source to the emergency room in the Children's Hospital, Geneva University Hospitals
Who may be able to join
- 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
- 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.
Who cannot join
- Unavailable blood
- Comorbidities predisposing to infections such as cancer, primary or secondary immunodeficiency, and iatrogenic immunosuppression
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Which Virus Leads to Viremia in Children With Fever Without Source and do New Biomarkers Correlate With Viral and Bacterial Infections?
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.
- Conditions
- Infectious Disease, Fever, Viremia
- Medical subject headings
- Communicable Diseases, Fever, Viremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Fever Without Source | Clinical diagnosis of FWS (fever of less than 7 days with no cause determined by the history and the physical exam). | |
| Healthy control | Children visiting the hospital due to a non-infectious, non inflammatory etiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 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)
Measured: 0-7 days after initiation of symptoms
Secondary outcomes (3)
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 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).
Measured: 0-7 days after initiation of symptoms
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 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).
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL).
- interferon γ-induced protein-10 (IP-10) (pg/mL).
- C-reactive protein (CRP) (mg/L).
Measured: 0-7 days after initiation of symptoms in cases with infection.
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.
Measured: 0-7 days after the initiation of symptoms
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study startNov 2015
- Primary completionJun 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Infectious DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- MeMed Diagnostics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University Hospital, Geneva
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03224026
- Sponsor's protocol ID
- MM-15082-Vir
- Status last verified
- Dec 2022
- First submitted
- 17 Jul 2017
- Last updated
- 6 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 25785720Colvin 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.
PubMed 23129086Ambrosioni 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.
PubMed 24382326L'Huillier AG, Mardegan C, Cordey S, Luterbacher F, Papis S, Hugon F, Kaiser L, Gervaix A, Posfay-Barbe K, Galetto-Lacour A. Enterovirus, parechovirus, adenovirus and herpes virus type 6 viraemia in fever without source. Arch Dis Child. 2020 Feb;105(2):180-186. doi: 10.1136/archdischild-2019-317382. Epub 2019 Aug 28.
PubMed 31462437
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Which Virus Leads to Viremia in Children With Fever Without Source and do New Biomarkers Correlate With Viral and Bacterial Infections?
- ClinicalTrials.gov ID
- NCT03224026
- Acronym / sponsor ID
- MM-15082-Vir
- Conditions
- Infectious Disease, Fever, Viremia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 206 participants (actual)
- Lead sponsor
- MeMed Diagnostics Ltd.Industry (pharma, biotech, devices)
- Collaborators
- University Hospital, Geneva
- Study start
- Nov 2015 (actual)
- Primary completion
- Jun 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fever Without Source | – | –Clinical diagnosis of FWS (fever of less than 7 days with no cause determined by the history and the physical exam). |
| Healthy control | – | –Children visiting the hospital due to a non-infectious, non inflammatory etiology |
Who may qualify
- Ages
- 1 day to 3 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Pediatric patients below three years old which were presented with a diagnosis of fever without source to the emergency room in the Children's Hospital, Geneva University Hospitals
Key inclusion criteria (6 listed)
- 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
- Age < 3 years old
- Informed consent (IC) given by parent or legal guardian
Key exclusion criteria (2 listed)
- Unavailable blood
- Comorbidities predisposing to infections such as cancer, primary or secondary immunodeficiency, and iatrogenic immunosuppression
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic accuracy compared to expert panel for bacterial versus viral.
Time frame: 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)
3 secondary outcomes
Diagnostic accuracy compared to microbiology gold standard for ruling out invasive bacterial infection.
Time frame: 0-7 days after initiation of symptoms
Comparison of biomarker levels in patients with different etiologies as classified by the expert panel or healthy.
Time frame: 0-7 days after initiation of symptoms in cases with infection.
Prevalence of viruses in children with fever without source.
Time frame: 0-7 days after the initiation of symptoms
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2023.
- Background: PubMed 25785720Oved 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.
- Background: PubMed 23129086Colvin 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.
- Background: PubMed 24382326Ambrosioni 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.
- Derived from this study: PubMed 31462437L'Huillier AG, Mardegan C, Cordey S, Luterbacher F, Papis S, Hugon F, Kaiser L, Gervaix A, Posfay-Barbe K, Galetto-Lacour A. Enterovirus, parechovirus, adenovirus and herpes virus type 6 viraemia in fever without source. Arch Dis Child. 2020 Feb;105(2):180-186. doi: 10.1136/archdischild-2019-317382. Epub 2019 Aug 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infectious Disease and Fever, run by MeMed Diagnostics Ltd. at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy compared to expert panel for bacterial versus viral. (time frame: 0-7 days after initiation of symptoms). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03224026, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2023.