Pragmatic Use of Next-generation Sequencing for Management of Drug-resistant Tuberculosis

Not Applicable

Recruiting

• Conditions: HIV Coinfection; Drug-resistant Tuberculosis; Cost-Benefit Analysis
• Interventions: Diagnostic Test: Targeted next-generation sequencing

• Registration Number: NCT05553236
• Lead Sponsor: University of California, San Francisco

Brief Summary

TS ELiOT is a stepped-wedge, cluster randomized trial assessing the effect of a next-generation sequencing-based strategy on rifampin-resistant tuberculosis management and patient outcomes.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-09-12
• Study First Submitted QC: 2022-09-20
• Study First Posted: 2022-09-23
• Study Start: 2024-08-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-14
• Last Update Posted: 2024-10-16
• Primary Completion: 2027-01
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2500

Inclusion Criteria

1. Active RR-TB diagnosed at a study facility during the study period
2. Positive Mtb culture, smear, or specimen derivative (e.g., GenoLyse remnant, Xpert cartridge extract)

Exclusion Criteria

1. Patient expects to relocate/move residence outside of the study region
2. Patient does not agree to participate in the study

In addition, participants later found to have isolates with rifamycin susceptibility on at least two additional tests (e.g., phenotypic DST, LPA, or sequencing) will be considered late exclusions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sequencing Intervention in addition to standard of care	Targeted next-generation sequencing	Batched targeted deep sequencing in addition to the locally accepted standard of care drug susceptibility determination of multidrug/extensively drug-resistant tuberculosis (M/XDR-TB)

Primary Outcome Measures

Name	Time	Method
Number of participants with prespecified end of treatment outcomes	At the anticipated completion of prescribed treatment, up to 18 months	The number of participants with each of the following prespecified end of treatment outcomes will be reported: cure, treatment completed, loss to follow up, treatment failure, death, transfer, and still on treatment.

Secondary Outcome Measures

Name	Time	Method
Number of participants with acquired drug resistance	At the anticipated completion of prescribed treatment, up to 18 months	Number of participants with M.tuberculosis acquiring additional drug resistance during treatment
12-month relapse-free survival	From completion of prescribed treatment to death or TB recurrence, up to 12 months	Length of time after treatment ends that the patient survives without TB recurrence
Time to effective treatment initiation with three drugs	From diagnosis to treatment initiation with at least three effective drugs, up to 18 months	Length of time from diagnosis to treatment initiation with at least three effective drugs to which M.tuberculosis is susceptible
Time to effective treatment initiation with four drugs	From diagnosis to treatment initiation with at least four effective drugs, up to 18 months	Length of time from diagnosis to treatment initiation with at least four effective drugs to which M.tuberculosis is susceptible
Exposure time to ineffective drugs	At the anticipated completion of prescribed treatment, up to 18 months	Cumulative length of time on individual drugs to which Mtb is found to be resistant, per participant
Time to culture conversion	From diagnosis to stable culture conversion, up to 9 months	Length of time from diagnosis to stable culture conversion, defined as the first of two (consecutive or non-consecutive) negative sputum cultures without an intervening positive culture, and/or visits wherein the participant is unable to produce sputum and has no signs of active TB, up to 9 months

Trial Locations

Locations (1)

South African National Health Laboratory Service; 🇿🇦 Cape Town, South Africa