Strengthening Evidence on Optimal Multidrug-resistant Tuberculosis Treatment Regimens

Study Overview
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Brief Summary
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This is a multisite prospective cohort study of patients with multidrug- or rifampin-resistant tuberculosis who are treated with an all-oral shortened regimen under routine program conditions in one of three countries (Peru, Lesotho, Kazakhstan).

Official Title
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Strengthening Evidence on Optimal Multidrug-resistant Tuberculosis Treatment Regimens Through Improved Epidemiologic Methods

Conditions
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HIV, Tuberculosis, Multidrug-Resistant

Intervention / Treatment
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* Drug: Bdq, Lzd, Lfx, Dlm, Cfz (9-12 months)
* Drug: Bdq, Lzd, Lfx, Cfz, Cs (9-12 months)
* Drug: Bdq, Lzd, Lfx, Z, Dlm (9-12 months)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients with pulmonary tuberculosis that is resistant to rifampin (RIF) or to both RIF and isoniazid who initiate an all-oral treatment regimen (short or long) under routine or operational conditions, per local country guidance, will be included. Exclusion Criteria: Exclusions are based on local guidance in each country. Currently, individuals with fluoroquinolone resistant tuberculosis are excluded from all-oral shortened treatment.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lesotho Cohort<br>200 patients receiving an all-oral shorter regimen in Lesotho under routine program conditions. | Drug: Bdq, Lzd, Lfx, Dlm, Cfz (9-12 months)<br>* Bdq, Lzd, Lfx, Dlm, Cfz for nine months, with extension to 12 months as needed<br>|
| Peru Cohort<br>50 patients receiving an all-oral shorter regimen in Peru under routine program conditions. | Drug: Bdq, Lzd, Lfx, Dlm, Cfz (9-12 months)<br>* Bdq, Lzd, Lfx, Dlm, Cfz for nine months, with extension to 12 months as needed<br>|
| Kazakhstan Cohort<br>550 patients receiving an all-oral shorter regimen in Kazakhstan under routine program conditions. | Drug: Bdq, Lzd, Lfx, Dlm, Cfz (9-12 months)<br>* Bdq, Lzd, Lfx, Dlm, Cfz for nine months, with extension to 12 months as needed<br>Drug: Bdq, Lzd, Lfx, Cfz, Cs (9-12 months)<br>* Bdq, Lzd, Lfx, Cfz, Cs for nine months, with extension to 12 months as needed<br>Drug: Bdq, Lzd, Lfx, Z, Dlm (9-12 months)<br>* Bdq, Lzd, Lfx, Z, Dlm for nine months, with extension to 12 months as needed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End-of-treatment outcome | Number of individuals experiencing each tuberculosis treatment outcome (cure, completion, death, failure, lost-to-follow-up), assessed at the end of treatment by a clinician, based on culture results | 9-12 months after treatment initiation | 
| Final tuberculosis treatment outcome | Number of individuals experiencing each final tuberculosis treatment outcome (cure, completion, death, failure, lost-to-follow-up, relapse), assessed at 6, 12, and 24 months by a clinician, based on culture results | 6-24 months after treatment completion | 
| Adverse events of interest | Assessed by a clinician based on symptomatology, subjective screening, and/or laboratory findings | Tuberculosis treatment, an average of 9 months |