Performance Evaluation of TB Breath- and Cough-testing Platforms

Performance Evaluation of Two Diagnostic Technologies for TB Detection Based Upon Breath Testing

This will be a prospective, multicentre study conducted to evaluate the diagnostic accuracy of two TB breath-based technologies independently of the manufacturers. Assay error and failure rates and device operational characteristics will also be assessed during this study. Participants will be enrolled in this study in line with FIND sample banking activities. Results from index tests will not be used to make clinical decisions. Participation in this study will not alter the standard of care.

Study Overview

• Status: Unknown
• Conditions: Diagnoses Diseases; Pulmonary TB
• Intervention / Treatment: Device: Rapid Biosensor Systems (RBS) TB Breathalyser; Device: eNose AeonoseTM

• Study Type: Observational
• Enrollment (Anticipated): 360

Contacts and Locations

• Study Contact: Name: Sonia Arafah; Phone Number: +41 (22) 710 05 90; Email: sonia.arafah@finddx.org

Study Locations

• South Africa
  • Cape Town, South Africa, 7700
    • Recruiting
    • Nolungile Clinic, University of Cape Town
    • Contact: Shireen Surtie
    • Contact: Pamela Jordan

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

All adult patients who have symptoms consistent with pulmonary TB presenting to health facilities during study period. Patients will be asked by study or non-study clinicians or staff if they would be interested in participating in the study. Interested individuals will be referred to study personnel for additional information and screening, if appropriate, samples will be obtained following the informed consent process.

Description

Inclusion Criteria:

• Symptoms suggesting pulmonary TB, i.e. persistent cough (generally > 3 weeks or as per local definition of TB suspect) and at least one other finding listed below:

  1. Persistent cough
  2. Fever
  3. Malaise
  4. Recent weight loss
  5. Night sweats
  6. Contact w/ active case
  7. Hemoptysis
  8. Chest pain
  9. Loss of appetite
  10. Other [specify]
• Provision of informed consent to sample collection, banking and HIV and breath-based assay testing
• Production of adequate quantity of sputum (sputum induction whenever possible)
• Adult age (>18 years old)

Exclusion Criteria:

• Participants receiving any anti-tuberculosis medication, including fluoroquinolone and aminoglycosides in the 60 days prior to enrolment.
• Participants with ONLY extra-pulmonary disease will be excluded.
• Participants for whom complete follow-up and a clear final diagnosis are judged to be difficult (e.g. residents elsewhere or about to move).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adults with pulmonary TB symptoms; All patients will be tested with both the reference and index TB diagnostic tests. Index test results will not be used to inform case management. All samples must be collected before the patient starts any form of TB treatment. Patients will be randomized to receive either the TB Breathalyser or AeonoseTM on Day 1, and will be tested with the remaining breath-test on Day 2. A follow-up evaluation will be required after 8 weeks for all patients who do not have microbiologic confirmation of TB (smear or culture). Two additional breath samples may also be collected upon follow-up.

Device: Rapid Biosensor Systems (RBS) TB Breathalyser; Rapid Biosensor Systems (RBS) recently developed a portable, non-invasive, rapid TB diagnostic 'Breathalyser' capable of diagnosing TB in patient breath samples collected while patients cough (Figure 1). The TB Breathalyser comprises a disposable, single-use sample collection tube and a multi-use reader. At the bottom of the collection tube is a glass bio-sensor coated with a biochemical sensor that is formulated to react with TB bacilli. Patients cough into the collection tube after nebulization with 0.9% saline solution. Following sample collection, the tube is placed into the reader, where a diode laser interrogates the biochemical coating in the sample collection tube and reports the presence of TB bacilli. The entire process takes about two minutes.; Device: eNose AeonoseTM; The eNose Company has also developed a hand-held, non-invasive rapid TB diagnostic 'electronic nose' (AeonoseTM) for TB detection based upon analysis of exhaled breath. After the device has been calibrated, the patient is instructed to breathe into the device through a mouthpiece for 5 minutes. Within the device is a micro-hotplate, metal-oxide sensor which behaves as a semiconductor at high temperature. Redox-reactions occurring at the sensor surface result in changes in resistance, with results read and interpreted by a phone application to confirm the presence of MTB.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiological TB Diagnosis	TB diagnosed by AFB smear microscopy or by one of two MGIT (liquid) or LJ (solid) cultures on enrollment or follow-up sputum sample	8 weeks

Collaborators and Investigators

• Sponsor: Find
• Collaborators: University of Cape Town; Universidad Peruana Cayetano Heredia
• Investigators: Study Director: Timothy C Rodwell, MD, PhD, MPH, Find

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 29, 2017
• Primary Completion (ANTICIPATED): December 1, 2017
• Study Completion (ANTICIPATED): December 1, 2017

Study Registration Dates

• First Submitted: January 17, 2017
• First Submitted That Met QC Criteria: January 18, 2017
• First Posted (ESTIMATE): January 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: P07212-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO