Cost-Benefit Analysis, Drug-resistant Tuberculosis, HIV Coinfection
Conditions
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.
Interventions
DIAGNOSTIC_TESTTargeted 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.
Sponsors
University of California, San Francisco
University of Stellenbosch
National Health Laboratory Service (NHLS), South Africa
National Institute for Communicable Diseases, South Africa
National Institute of Allergy and Infectious Diseases (NIAID)
Find
Translational Genomics Research Institute
University Hospital Heidelberg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
South Africa
Contacts
CONTACTJohn Z Metcalfe, MD, PhD
CONTACTRob Warren, PhD
PRINCIPAL_INVESTIGATORJohn Z Metcalfe, MD, PhD
University of California, San Francisco
Outcome results
None listed