Evaluation of Centralised TB Assay Solutions

Completed

• Conditions: Tuberculosis; Drug-resistant Tuberculosis

• Registration Number: NCT04147676
• Lead Sponsor: Foundation for Innovative New Diagnostics, Switzerland

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-20
• Status Verified: 2019-10
• Study First Submitted: 2019-10-30
• Study First Submitted QC: 2019-10-30
• Study First Posted: 2019-11-01
• Primary Completion: 2023-04-17
• Study Completion: 2023-09-01
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1050

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Diagnostic accuracy for MTB detection	four to six months	clinical sensitivity and specificity by smear-status measured against mycobacterial culture as the reference standard.
Diagnostic accuracy for RIF/INH detection	four to six months	clinical point estimates of sensitivity and specificity measured against a composite reference standard of phenotypic DST and targeted sequencing.

Secondary Outcome Measures

Name	Time	Method
Operational characteristics:	four to six months	description of operator experience with the assays through daily observed usage and user appraisal questionnaires.

Trial Locations

Locations (6)

National Center for Tuberculosis and Lung Diseases; 🇬🇪 Tbilisi, Georgia

Division of Wits Health Consortium (DMMH); 🇿🇦 Johannesburg, South Africa

National Institute for Research in Tuberculosis; 🇮🇳 Chennai, India

Forschungszentrum Borstel. Leibniz Lungenzentrum (Borstel); 🇩🇪 Borstel, Germany

Indian Council of Medical Research (ICMR) Regional Medical Research Centre; 🇮🇳 Bhubaneswar, India

Institute of Phthisiopneumology "Ch. Draganiuc" (PPI NRL), Moldova; 🇲🇩 Chisinau, Moldova, Republic of