Evaluation of Centralised TB Assay Solutions


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.

Full Title of Study: “Multicentre Trial to Assess the Performance of Centralized Assay Solutions for Detection of MTB and Resistance to Rifampin and Isoniazid”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: August 1, 2020

Arms, Groups and Cohorts

  • TB suspects
    • Sputum specimens will be collected from TB suspects enrolled in the study. The specimens will be tested with Roche cobas MTB – for the detection of Mycobacterium tuberculosis complex 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 Hain FluoroType MTBDR – for the detection of Mycobacterium tuberculosis complex and the detection of resistance to rifampicin and isoniazid

Clinical Trial Outcome Measures

Primary Measures

  • Diagnostic accuracy for MTB detection
    • Time Frame: 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
    • Time Frame: four to six months
    • clinical point estimates of sensitivity and specificity measured against a composite reference standard of phenotypic DST and targeted sequencing.

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Foundation for Innovative New Diagnostics, Switzerland
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Margaretha de Vos, PhD, +41 (0) 22 749 29 31, margaretha.devos@finddx.org

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