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

NCT05553236 | Recruiting

• 2 other identifiers: AI153213R01AI153213
• Study Type: interventional
• Target: 2,500
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Coinfection; Cost-Benefit Analysis; Drug-resistant Tuberculosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 12-month relapse-free survival

  From completion of prescribed treatment to death or TB recurrence, up to 12 months

• Exposure time to ineffective drugs

  At the anticipated completion of prescribed treatment, up to 18 months

• Number of participants with acquired drug resistance

  At the anticipated completion of prescribed treatment, up to 18 months

• Time to effective treatment initiation with three drugs

  From diagnosis to treatment initiation with at least three effective drugs, up to 18 months

• Time to effective treatment initiation with four drugs

  From diagnosis to treatment initiation with at least four effective drugs, up to 18 months

Other Outcomes (2)

• Number of participants with clinical uptake of sequencing intervention results

  At the anticipated completion of prescribed treatment, up to 18 months

• Cost-effectiveness of the sequencing intervention

  At the anticipated completion of prescribed treatment, up to 18 months

Study Arms (2)

Sequencing Intervention in addition to standard of care

EXPERIMENTAL

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)

Diagnostic Test: Targeted next-generation sequencing

Standard of Care

NO INTERVENTION

Locally accepted standard of care which is consistent with the WHO recommendations for the drug susceptibility determination of M/XDR-TB

Interventions

Targeted next-generation sequencing DIAGNOSTIC_TEST

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.

Sequencing Intervention in addition to standard of care

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

South African National Health Laboratory Service

Cape Town, South Africa

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; HIV Infections

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• John Z Metcalfe, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Z Metcalfe, MD, PhD

CONTACT

+14152068314; john.metcalfe@ucsf.edu

Rob Warren, PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 23, 2022
• Study Start: August 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)