Strengthening Evidence on Optimal Multidrug-resistant Tuberculosis Treatment Regimens (STEM-TB)

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

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).

Study Overview

• Status: Recruiting
• Conditions: HIV; Tuberculosis, Multidrug-Resistant
• Intervention / Treatment: 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)

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: Molly F Franke, ScD; Phone Number: 617-432-5224; Email: molly_franke@hms.harvard.edu

Study Locations

• Kazakhstan
  • Almaty, Kazakhstan
    • Recruiting
    • Partners In Health, Kazakhstan
    • Contact: Yerkebulan Algozhin, MD
• Lesotho
  • Maseru, Lesotho
    • Recruiting
    • Partners In Health, Lesotho
    • Contact: Mikanda Kunda, MD
• Peru
  • Lima, Peru
    • Recruiting
    • Socios En Salud
    • Contact: Leonid Lecca, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study will prospectively follow an observational cohort patients with confirmed MDR-TB who initiate one of the following MDR-TB regimens of interest: (1) an individualized 18-24 month all-oral regimen containing BDQ and/or DLM, designed according to 2019 WHO guidance (Lesotho); or (2) a standardized, shortened all-oral regimen containing BDQ or DLM.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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
Adverse events of interest	Assessed by a clinician based on symptomatology, subjective screening, and/or laboratory findings	Tuberculosis treatment, an average of 9 months
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

Collaborators and Investigators

• Sponsor: Harvard Medical School (HMS and HSDM)
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Partners in Health; Socios En Salud Sucursal, Peru

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 23, 2023

Study Record Updates

• Last Update Posted (Estimated): June 13, 2023
• Last Update Submitted That Met QC Criteria: June 11, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Multidrug-Resistant
• Other Study ID Numbers: R01AI146095 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No