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

Primary Purpose

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

Status
Not yet recruiting
Phase
Not Applicable
Locations
South Africa
Study Type
Interventional
Intervention
Targeted next-generation sequencing
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Drug-resistant Tuberculosis

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • South African National Health Laboratory Service

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Sequencing Intervention in addition to standard of care

Standard of Care

Arm Description

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)

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

12-month relapse-free survival
Length of time after treatment ends that the patient survives without TB recurrence
Exposure time to ineffective drugs
Cumulative length of time on individual drugs to which Mtb is found to be resistant, per participant
Number of participants with acquired drug resistance
Number of participants with M.tuberculosis acquiring additional drug resistance during treatment
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
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
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

Full Information

First Posted
September 12, 2022
Last Updated
February 24, 2023
Sponsor
University of California, San Francisco
Collaborators
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
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1. Study Identification

Unique Protocol Identification Number
NCT05553236
Brief Title
Pragmatic Use of Next-generation Sequencing for Management of Drug-resistant Tuberculosis
Acronym
TSELiOT
Official Title
Targeted Sequencing to Enhance, Liberate, and Optimize Treatment of Drug-resistant Tuberculosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 31, 2023 (Anticipated)
Primary Completion Date
January 2027 (Anticipated)
Study Completion Date
January 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug-resistant Tuberculosis, HIV Coinfection, Cost-Benefit Analysis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sequencing Intervention in addition to standard of care
Arm Type
Experimental
Arm Description
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)
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Locally accepted standard of care which is consistent with the WHO recommendations for the drug susceptibility determination of M/XDR-TB
Intervention Type
Diagnostic Test
Intervention Name(s)
Targeted next-generation sequencing
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants with prespecified end of treatment outcomes
Description
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.
Time Frame
At the anticipated completion of prescribed treatment, up to 18 months
Secondary Outcome Measure Information:
Title
12-month relapse-free survival
Description
Length of time after treatment ends that the patient survives without TB recurrence
Time Frame
From completion of prescribed treatment to death or TB recurrence, up to 12 months
Title
Exposure time to ineffective drugs
Description
Cumulative length of time on individual drugs to which Mtb is found to be resistant, per participant
Time Frame
At the anticipated completion of prescribed treatment, up to 18 months
Title
Number of participants with acquired drug resistance
Description
Number of participants with M.tuberculosis acquiring additional drug resistance during treatment
Time Frame
At the anticipated completion of prescribed treatment, up to 18 months
Title
Time to effective treatment initiation with three drugs
Description
Length of time from diagnosis to treatment initiation with at least three effective drugs to which M.tuberculosis is susceptible
Time Frame
From diagnosis to treatment initiation with at least three effective drugs, up to 18 months
Title
Time to effective treatment initiation with four drugs
Description
Length of time from diagnosis to treatment initiation with at least four effective drugs to which M.tuberculosis is susceptible
Time Frame
From diagnosis to treatment initiation with at least four effective drugs, up to 18 months
Title
Time to culture conversion
Description
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
Time Frame
From diagnosis to stable culture conversion, up to 9 months
Other Pre-specified Outcome Measures:
Title
Number of participants with clinical uptake of sequencing intervention results
Description
The number of sequencing intervention results with treatment regimen adjustment where appropriate treatment change is indicated
Time Frame
At the anticipated completion of prescribed treatment, up to 18 months
Title
Cost-effectiveness of the sequencing intervention
Description
Costs of necessary personnel, consumables, facility, logistics, and per unit tests
Time Frame
At the anticipated completion of prescribed treatment, up to 18 months

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: Patient expects to relocate/move residence outside of the study region 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Z Metcalfe, MD, PhD
Phone
+14152068314
Email
john.metcalfe@ucsf.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Rob Warren, PhD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Z Metcalfe, MD, PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
South African National Health Laboratory Service
City
Cape Town
Country
South Africa
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robin M Warren, PhD
First Name & Middle Initial & Last Name & Degree
Nabila Ismail, PhD
Email
nabilai@sun.ac.za

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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