Evaluation of Centralised TB Assay Solutions

Tuberculosis Clinical Trial

Official title:

Multicentre Trial to Assess the Performance of Centralized Assay Solutions for Detection of MTB and Resistance to Rifampin and Isoniazid

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04147676
• Other study ID #: 7213-2/1
• Status: Completed
• Start date: May 20, 2019
• Est. completion date: September 1, 2023

Study information

• Verified date: October 2019
• Source: Foundation for Innovative New Diagnostics, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1050
• Est. completion date: September 1, 2023
• Est. primary completion date: April 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patients are eligible to be included as trial participants only if all of the following inclusion criteria apply:

• 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

Exclusion Criteria:

Participants are excluded from the trial if any of the following exclusion criteria apply:

• 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

Related Conditions & MeSH terms

• Drug-resistant Tuberculosis
• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Locations

Country	Name	City	State
Georgia	National Center for Tuberculosis and Lung Diseases	Tbilisi
Germany	Forschungszentrum Borstel. Leibniz Lungenzentrum (Borstel)	Borstel
India	Indian Council of Medical Research (ICMR) Regional Medical Research Centre	Bhubaneswar
India	National Institute for Research in Tuberculosis	Chennai
Moldova, Republic of	Institute of Phthisiopneumology "Ch. Draganiuc" (PPI NRL), Moldova	Chisinau
South Africa	Division of Wits Health Consortium (DMMH)	Johannesburg

Sponsors (1)

Lead Sponsor	Collaborator
Foundation for Innovative New Diagnostics, Switzerland

Countries where clinical trial is conducted

Georgia,  Germany,  India,  Moldova, Republic of,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic accuracy for MTB detection	clinical sensitivity and specificity by smear-status measured against mycobacterial culture as the reference standard.	four to six months
Primary	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	Operational characteristics:	description of operator experience with the assays through daily observed usage and user appraisal questionnaires.	four to six months