Clinical trial NCT04147676: Evaluation of Centralised TB Assay Solutions
Official title: Multicentre Trial to Assess the Performance of Centralized Assay Solutions for Detection of MTB and Resistance to Rifampin and Isoniazid
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Drug-resistant Tuberculosis
Lead sponsor: Foundation for Innovative New Diagnostics, Switzerland
Sponsor class: OTHER
First posted: 2019-11-01
Enrollment: 1050
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Diagnostic accuracy for MTB detection
timeFrame: four to six months
measure: Diagnostic accuracy for RIF/INH detection
timeFrame: four to six months
Secondary outcomes:
measure: Operational characteristics:
timeFrame: four to six months
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: National Center for Tuberculosis and Lung Diseases
city: Borstel
country: Germany
facility: Forschungszentrum Borstel. Leibniz Lungenzentrum (Borstel)
city: Bhubaneswar
country: India
facility: Indian Council of Medical Research (ICMR) Regional Medical Research Centre
city: Chennai
country: India
facility: National Institute for Research in Tuberculosis
city: Chisinau
country: Moldova, Republic of
facility: Institute of Phthisiopneumology "Ch. Draganiuc" (PPI NRL), Moldova
city: Johannesburg
country: South Africa
facility: Division of Wits Health Consortium (DMMH)
Study officials:
References: