Evaluating a Host-response Based Diagnostic for Distinguishing Between Bacterial and Viral Etiology in Patients With Lower Respiratory Tract Infection (LRTI) (OBSERVER)

A Multi-center, Prospective, Validation Study to Assess the Accuracy of a Host-response Based Diagnostic for Distinguishing Between Bacterial and Viral Etiology in Adult Patients With Lower Respiratory Tract Infections

The purpose of this study is to validate the diagnostic accuracy of a novel host-response based diagnostic tool for differentiating between bacterial and viral etiologies in adult patients aged 18 years and older with clinical suspicion of lower respiratory tract infections (LRTI)

Study Overview

• Status: Completed
• Conditions: Pneumonia; Chronic Obstructive Pulmonary Disease (COPD); Lower Respiratory Tract Infection; Acute Bronchitis; Upper Respiratory Tract Infection

• Study Type: Observational
• Enrollment (Actual): 583

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will include eligible patients aged 18 years and older of both genders that attend the emergency department or affiliated community clinics due to a suspected LRTI, or due to a non-infectious disease.

Description

Inclusion Criteria:

• Patients aged 18 years and older who agree (or their legal guardian agree) to sign an informed consent will be eligible for inclusion.

• The LRTI cohorts should also fulfill the following criteria:

  • Peak measured (not tactile, self-reported acceptable) temperature ≥ 37.8°C (100°F) within the last 7 days (AND)
  • Symptoms duration ≤7 days (AND)
  • Clinical suspicion of LRTI or pneumonia

Exclusion Criteria:

• Oral/intravenous/intramuscular antibiotic treatment of over 48/12/12 hours' duration at time of enrollment (respectively), unless temperature ≥ 37.8°C was measured within the last 2 days
• Another episode of an acute infection during the last 2 weeks
• Congenital immune deficiency (CID)
• A proven or suspected human immunodeficiency virus (HIV)-1, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
• Active malignancy
• Pregnancy

• 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
  • Intravenous immunoglobulin (IVIG)
  • Cyclosporine, Cyclophosphamide, Tacrolimus
  • Granulocyte/Monocyte colony stimulating factor (G/GM-CSF)
  • Anti-Tumor Necrosis Factor (TNF) agents
  • Interferon (of all kinds)

• Other severe illnesses that affect life expectancy and quality of life such as:

  • Moderate to severe psychomotor retardation
  • Post-transplant patients (including solid organs, allogeneic/autologous stem cell transplantation)
  • Moderate to severe congenital metabolic disorder

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
LRTI patients; Patients with suspicion of LRTI, excluding episodes of COPD exacerbations
Non-infectious patients; Afebrile patients with no apparent infectious disease
LRTI patients with COPD; Patients with suspicion of LRTI in a sub-group of patients with COPD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To externally validate the diagnostic accuracy of a host-response based diagnostic tool called ImmunoXpert™, for differentiating between bacterial and viral etiologies in adult patients aged 18 years and older with clinical suspicion of LRTI	0-6 days after the initiation of symptoms

Secondary Outcome Measures

Outcome Measure	Time Frame
To compare the diagnostic accuracy of ImmunoXpert™ to currently available lab measures (WBC, ANC, PCT, CRP), using sensitivity and specificity measures and predetermined cutoffs	0-6 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	0-6 days after the initiation of symptoms
To estimate the potential improvement in health and economic outcomes following the usage of ImmunoXpert™ compared to current practice	0-6 days after the initiation of symptoms
To estimate the diagnostic accuracy of ImmunoXpert™ in differentiating between infectious vs non-infectious patients	0-6 days after the initiation of symptoms

Collaborators and Investigators

• Sponsor: MeMed Diagnostics Ltd.
• Collaborators: Rambam Health Care Campus; Rabin Medical Center; European Commission; Carmel Medical Center
• Investigators: Principal Investigator: Mical Paul, MD, Rambam Health Care Campus

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.
• 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.
• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 10, 2017
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): January 7, 2020

Study Registration Dates

• First Submitted: January 4, 2017
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (ESTIMATE): January 5, 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: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Infections; Communicable Diseases; Respiratory Tract Infections; Bronchitis
• Other Study ID Numbers: MM-1005-OB