10.3 Treatment regimens in operational research conditions

MDR/RR-TB patients can be treated under operational research conditions with short regimens other than the standard STRs. Whatever the rationale or results of operational research, they should be communicated as they may complement those of clinical trials.

10.3.1 Operational research conditions

The requirements for conducting operational research include:

• A study protocol including 12-month post-end-of-treatment follow-up.
• A clinical treatment guide.
• A patient consent process.
• Approval by an ethics review board and Ministry of Health.
• A pharmacovigilance system (core aDSM a Citation a. World Health Organization. Active tuberculosis drug-safety monitoring and management (aDSM). Framework for implementation. WHO, Geneva, 2015.
  https://iris.who.int/bitstream/handle/10665/204465/WHO_HTM_TB_2015.28_eng.pdf?sequence=1 ).

Study protocol templates are available from the Global Drug-resistant TB Initiative (GDI) b Citation b. Global Drug Initiative-StopTB Partnership: The Evaluation of Effectiveness and Safety of Novel Shorter Treatment Regimens for Multidrug-Resistant Tuberculosis Operational Research Protocol Template, May 2018.
http://www.stoptb.org/wg/mdrtb/assets/documents/GDI%20OR%20generic%20protocol%20final.pdf and WHO c Citation c. World Health Organization. ShORRT. (Short, all-Oral Regimens for Rifampicin-resistant Tuberculosis) Research Package. Version 4 June 2020.
https://tdr.who.int/docs/librariesprovider10/shorrt-initiative/shorrt-generic-protocol-june2020_en.pdf?sfvrsn=df85f6c1_3 .

10.3.2 Treatment regimens under investigation

The following regimens are examples of standardized regimens that can be used under operational research conditions. These regimens have been reviewed by scientific committees and have been tested, or are currently being tested, in clinical trials.

For FQ-susceptible MDR/RR-TB patients

• The five endTB trial experimental regimens [1] Citation 1. https://clinicaltrials.gov/ct2/show/NCT02754765 :
  • 9Bdq-Lzd-Mfx-Z
  • 9Bdq-Cfz-Lzd-Lfx-Z
  • 9Bdq-Dlm-Lzd-Lfx-Z
  • 9Dlm-Cfz-Lzd-Lfx-Z
  • 9Dlm-Cfz-Mfx-Z
• The TB-PRACTECAL regimen that includes clofazimine [2] Citation 2. https://clinicaltrials.gov/ct2/show/NCT02589782 : 6Bdq-Pa-Lzd-Cfz (BPaLC regimen)

For FQ-resistant MDR/RR-TB patients

• The endTB-Q trial regimen: 6 or 9Bdq-Dlm-Lzd-Cfz [3] Citation 3. https://clinicaltrials.gov/ct2/show/NCT03896685
• The TB-PRACTECAL regimen that includes clofazimine: 6Bdq-Pa-Lzd-Cfz (BPaLC regimen)