Evaluation of Centralised TB Assay Solutions

NCT04147676 | Completed

• 1 other identifier: 7213-2/1
• Study Type: observational
• Target: 1,050
• Locations: 5 countries
• Sites: 6

Brief Summary

Tuberculosis (TB) remains a life-threatening disease partly due to increasing incidence of multidrug and extensively drug-resistant TB. Diagnostic based on culture and conventional drug susceptibility testing using media take several weeks leading to prolonged periods of ineffective therapy and ongoing transmission. Development of rapid molecular diagnostic tests for the identification of Mycobacterium tuberculosis (MTB) and drug resistance has become a high priority. The Xpert® MTB/RIF Assay does not provide information on INH-resistance and the LPA is only recommended for use in smear-positive samples, complex to perform and requires manual interpretation. Several novel assays have been recently developed/CE-marked offering high sample throughput and higher sensitivity for detection of MTB, RIF- and INH-resistance in centralized laboratories. However, published data on their performance and operational characteristics is extremely limited. This is a prospective, multicentre, diagnostic accuracy trial in which the performance of centralised TB assay solutions will be assessed at the intended setting of use with culture, phenotypic DST and sequencing as reference standard. Potential trial participants will be identified at participating TB clinics or hospitals (enrolment sites). Sputum samples will be collected and transported to the associated TB reference laboratories (testing sites). In order for the results of this trial to be generalizable, adults with symptoms compatible with pulmonary TB undergoing evaluation will be screened for inclusion at geographically diverse participating centres in high burden TB countries. Additionally, to supplement the drug-resistant cases to timely achieve accurate performance estimates, well-characterized frozen sputum samples from the FIND specimen bank will be used.

Conditions

Tuberculosis; Drug-resistant Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Diagnostic accuracy for MTB detection

  clinical sensitivity and specificity by smear-status measured against mycobacterial culture as the reference standard.

  four to six months

• Diagnostic accuracy for RIF/INH detection

  clinical point estimates of sensitivity and specificity measured against a composite reference standard of phenotypic DST and targeted sequencing.

  four to six months

Secondary Outcomes (1)

• Operational characteristics:

  four to six months

Study Arms (1)

TB suspects

Sputum specimens will be collected from TB suspects enrolled in the study. The specimens will be tested with 1. Roche cobas MTB - for the detection of Mycobacterium tuberculosis complex 2. Roche cobas MTB-RIF/INH - all specimens that are Mycobacterium tuberculosis complex positive will be reflexed to the Roche cobas MTB-RIF/INH test for the detection of resistance to rifampicin and isoniazid 3. Hain FluoroType MTBDR - for the detection of Mycobacterium tuberculosis complex and the detection of resistance to rifampicin and isoniazid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients in whom pulmonary TB is suspected. Additionally, well-characterized RIF-resistant and INH-resistant samples will be used to supplement drug-resistant cases.

You may qualify if:

• Aged ≥18 years
• Clinical suspicion of pulmonary TB including cough ≥2 weeks (or any duration if HIV positive ) and ≥1 other symptom typical of pulmonary TB listed below:
• Fever
• Malaise
• Recent weight loss
• Night sweats
• Contact with active case
• Haemoptysis
• Chest pain
• Loss of appetite

You may not qualify if:

• Unwilling or unable to provide informed consent
• Unwilling to provide four sputum specimens at enrolment i.e. 2x sputa on day 1 and 2x sputa on day 2 (up to 1 week from enrolment)
• Patients with only extra-pulmonary TB signs \& symptoms
• Receipt of any dose of TB treatment within 6 months prior to enrolment

Sponsors & Collaborators

• Foundation for Innovative New Diagnostics, Switzerland: lead

Study Sites (6)

National Center for Tuberculosis and Lung Diseases

Tbilisi, Georgia

Location

Forschungszentrum Borstel. Leibniz Lungenzentrum (Borstel)

Borstel, 23845, Germany

Location

Indian Council of Medical Research (ICMR) Regional Medical Research Centre

Bhubaneswar, 751023, India

Location

National Institute for Research in Tuberculosis

Chennai, 600031, India

Location

Institute of Phthisiopneumology "Ch. Draganiuc" (PPI NRL), Moldova

Chisinau, 2025, Moldova

Location

Division of Wits Health Consortium (DMMH)

Johannesburg, 2193, South Africa

Location

Biospecimen

Retention: SAMPLES WITH DNA

Sputum specimens M. tuberculosis cultures isolates from patient specimens

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Multidrug-Resistant

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: November 1, 2019
• Study Start: May 20, 2019
• Primary Completion: April 17, 2023
• Study Completion: September 1, 2023
• Last Updated: November 18, 2023

Record last verified: 2019-10

Locations

MO (1); GE (1); DE (1); IN (2); ZA (1)