Assess a Diagnostic Tool to Distinguish Between Bacterial and Viral Infection

Lower Respiratory Tract Infection Clinical Trial

— OPPORTUNITY  

Official title:

Prospective, Blinded Validation Study to Assess Accuracy of a Diagnostics for Distinguishing Between Bacterial and Viral Etiology in Pediatric Patients With Lower Respiratory Tract Infections and Fever Without Source

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01931254
• Other study ID #: MM-1003-BV
• Status: Completed
• Phase: N/A
• First received: August 22, 2013
• Last updated: November 27, 2017
• Start date: October 2013
• Est. completion date: November 2016

Study information

• Verified date: November 2017
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In the past 70 years antibiotics have served as the first line of defense against infectious diseases. However, antibiotics are only effective against bacterial infections and are not the solution for infections caused by viruses such as common colds or flu. Despite their contribution to healthcare, antibiotics are currently recognized as the most misused drugs in the world with global overuse estimated at 40%-70%, mostly due to the ineffectiveness of current diagnostic solutions to distinguish between bacterial and viral infections. Antibiotics misuse often causes preventable adverse events that impact patient care and lead to the emergence of antibiotic-resistant bacteria, one of the major threats to global health today. To address these challenges, MeMed has been developing the ImmunoDx™, a novel technology that relies on the best available detection system for differentiating between viruses and bacteria - the body's own immune system. The ImmunoDx™ technology employs a simple blood test that provides the physician, within two-hours, the information he needs to decide whether to treat the patient with antibiotics or not. This technology has been tested on over 1000 patients of different ages and diseases and was found to be highly accurate and safe. The current study is a non-interventional study and the participants do not receive any investigational drug nor any experimental examination or procedure. Therefore, the collected data in this study will not affect the diagnosis, prognosis, or treatment of the participants. Participation includes the collection of a teaspoon of blood and collection of a specimen using a nasal swab. These procedures are common in the clinical practice and are widely performed and possess no significant risk. By participating in the study, the subjects impact the development of the ImmunoDx™ technology, which is expected to enable a future faster and more accurate diagnosis of infectious diseases as well as more appropriate prescription of antibiotics. This will open the way to improve treatment decisions in millions of patients around the world.

Description:

This is a prospective clinical validation study of a novel in-vitro diagnostic (IVD) assay that will enroll 830 pediatric patients. The study will be conducted in two stages: In stage A 50 patients will be enrolled with the aim of verifying proper protocol execution including proper collection of patient samples, accurate data retrieval and precise etiology determination. In stage B 780 patients will be enrolled with the aim of blinded validation of the host-response based diagnostics using a fresh independent cohort of patients. Patients enrolling into the study will be managed according to the current standard of care (GCP) and per standard institutional procedures. Participation in this study requires the collection of an additional blood sample and a nasal swab sampling.

The investigated assay requires the measurement of three host-related, blood-based, protein biomarkers that are being integrated using a logistic regression formula into a single score. Based on this score, each patient is classified into one of three categories: (i) bacterial immune response (i.e., pure bacterial infections and mixed bacterial and viral co-infection), (ii) viral immune response, and (iii) marginal immune response (inconclusive or non-infectious). It is estimated that 10-20% of the infected patients will have a marginal immune response. A composite reference standard will be used in order to determine the diagnosis of each patient. Specifically, all the clinical, radiological, microbiological and laboratory data of each patient, will be recorded in a dedicated eCRF. Based on this data, the diagnosis of each patient will be determined by a panel of three independent pediatricians. Each pediatrician will be blinded to the diagnosis of his peers and to the assay results. In the current study, unanimous agreement between the experts ("consensus agreement") will be considered as the true diagnosis for the purpose of computing the assay performance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 777
• Est. completion date: November 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 60 Months

Eligibility

Inclusion Criteria:

Patients aged 1 to 60 months whose their legal guardian agrees to sign an informed consent will be eligible for inclusion.

The infectious disease group (n = 690) should also fulfill the following criteria:

• Peak temperature = 38°C (100.4°F) (AND)

• Symptoms duration = 6 days (AND)

• Clinical suspicion of LRTI (OR)

• Fever without a clear source where no localizing sign of infection are present at the emergency department

The non-infectious disease control group will include:

• Patients with a non-infectious disease (n = 140)

Exclusion Criteria:

Patients who will meet one or more of the following criteria will be excluded from the study:

• Another episode of febrile infection during the past 3 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

Current treatment with immune-suppressive or immune-modulating therapies including without limitations:

1. Use of high dose steroids >1 mg/kg/day prednisone or equivalent in the past two weeks

2. Monoclonal antibody administration

3. Intravenous immunoglobulin (IVIG)

4. Cyclosporine

5. G/GM-CSF

6. Anti-TNF agents

7. Interferon (of all kinds)

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

• Moderate to severe psychomotor retardation

• Thalassemia Major

• Moderate to severe congenital metabolic disorder

Related Conditions & MeSH terms

• Communicable Diseases
• Fever
• Infection
• Lower Respiratory Tract Infection
• Respiratory Tract Infections
• Unspecified Fever

Locations

Country	Name	City	State
Israel	Pediatrics Department, Hillel Yaffe Medical center (HYMC),	Hadera
Israel	Pediatric Emergency Department (ED), Bnei Zion Medical Center (BZMC),	Haifa
Netherlands	UMC Utrecht, Wilhelmina Kinderziekenhuis	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	MeMed Diagnostics Ltd.

Countries where clinical trial is conducted

Israel,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	sensitivity / specificity diagnostic tool	To determine the sensitivity and specificity of a host-response based diagnostics in differentiating between bacterial and viral etiology of pediatric patients aged 1 to 60 months with LRTI or FWS.	One year
Primary	sensitivity / specificity diagnostic tool	To determine the sensitivity and specificity of a host-response based diagnostics in differentiating between bacterial and viral etiology of pediatric patients aged 2 to 60 months with LRTI or FWS.	one year
Secondary	sensitivity /specificity diagnostic tool	To determine the sensitivity and specificity of a host-response based diagnostics in differentiating between infectious and non-infectious disease of pediatric patients aged 2 to 60 months.	One year