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

Cost-Benefit Analysis Clinical Trial

— TSELiOT  

Official title:

Targeted Sequencing to Enhance, Liberate, and Optimize Treatment of Drug-resistant Tuberculosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05553236
• Other study ID #: AI153213
• Secondary ID: R01AI153213
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 28, 2024
• Est. completion date: January 2027

Study information

• Verified date: May 2024
• Source: University of California, San Francisco
• Contact: John Z Metcalfe, MD, PhD
• Phone: +14152068314
• Email: john.metcalfe[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2500
• Est. completion date: January 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Coinfection
• Cost-Benefit Analysis
• Drug-resistant Tuberculosis
• HIV Coinfection
• HIV Infections
• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Intervention

Diagnostic Test:
• Targeted next-generation sequencing
During intervention periods, an additional patient sample derived from routinely collected specimens will be processed by a local technician. Extracted DNA extracted from these samples will be batched on a regular basis for targeted deep sequencing. Sequencing results will be regularly transmitted to a clinical advisory committee.

Locations

Country	Name	City	State
South Africa	South African National Health Laboratory Service	Cape Town

Sponsors (8)

Lead Sponsor	Collaborator
University of California, San Francisco	Find, National Health Laboratory Service (NHLS), South Africa, National Institute for Communicable Diseases, South Africa, National Institute of Allergy and Infectious Diseases (NIAID), Translational Genomics Research Institute, University Hospital Heidelberg, University of Stellenbosch

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with clinical uptake of sequencing intervention results	The number of sequencing intervention results with treatment regimen adjustment where appropriate treatment change is indicated	At the anticipated completion of prescribed treatment, up to 18 months
Other	Cost-effectiveness of the sequencing intervention	Costs of necessary personnel, consumables, facility, logistics, and per unit tests	At the anticipated completion of prescribed treatment, up to 18 months
Primary	Number of participants with prespecified end of treatment outcomes	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.	At the anticipated completion of prescribed treatment, up to 18 months
Secondary	12-month relapse-free survival	Length of time after treatment ends that the patient survives without TB recurrence	From completion of prescribed treatment to death or TB recurrence, up to 12 months
Secondary	Exposure time to ineffective drugs	Cumulative length of time on individual drugs to which Mtb is found to be resistant, per participant	At the anticipated completion of prescribed treatment, up to 18 months
Secondary	Number of participants with acquired drug resistance	Number of participants with M.tuberculosis acquiring additional drug resistance during treatment	At the anticipated completion of prescribed treatment, up to 18 months
Secondary	Time to effective treatment initiation with three drugs	Length of time from diagnosis to treatment initiation with at least three effective drugs to which M.tuberculosis is susceptible	From diagnosis to treatment initiation with at least three effective drugs, up to 18 months
Secondary	Time to effective treatment initiation with four drugs	Length of time from diagnosis to treatment initiation with at least four effective drugs to which M.tuberculosis is susceptible	From diagnosis to treatment initiation with at least four effective drugs, up to 18 months
Secondary	Time to culture conversion	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	From diagnosis to stable culture conversion, up to 9 months