Overview
To determine if a high-dose first-line regimen is non-inferior (non-inferiority margin 10%) in terms of safety to the same regimen at regular dosing, in previously treated patients with rifampicin-susceptible recurrent Tuberculosis (TB).
Description
Stage 1: This is a pragmatic open-label multi-stage randomized clinical trial. Potential participants will be screened and enrolled in Damien Foundation (DF) clinics participating in the trial.
First we will perform a two-arm study with 6EHRZ as control arm and 6EH³R³Z as intervention arm. If at interim analysis the intervention arm is not considered to be non-inferior to the control arm, the intervention stops and enrolment will continue in a an adapted intervention arm and the control arm (6EHRZ). Otherwise, enrolment continues to 6EHRZ and 6EH³R³Z.
Observational study (stage 2): The DSMB members agreed due to safety concerns to continuing the study as a cohort with only the control arm. The control regimen will remain the same (6EHRZ).
As per routine practice, during treatment patients are in daily contact with the direct observed therapy (DOT) supervisor and minimally monthly clinic visits are scheduled for monitoring of safety and treatment response.
Additionally, liver function tests will be performed at fixed intervals during treatment. Six month and one year after treatment completion or cure the patient will be checked for relapse with systematic sputum acid-fast bacilli (AFB)-microscopy and TB culture.
Eligibility
Inclusion Criteria:
- All newly registered patients with smear-positive recurrent pulmonary TB
- Adults as well as children (no age limit)
- Able and willing to provide written informed consent
- Added for stage 2: lives within 5 km of a health facility with a medical doctor
Exclusion Criteria:
- All patients with TB initially resistant to rifampicin on Xpert MTB/RIF testing
- Patients transferred to a health facility not supported by the Damien Foundation
- Patients previously enrolled in the trial, and with another episode of rifampicin-susceptible TB during the study period
- Those with grade III elevation of liver function tests at baseline, or with clinically active liver disease at screening
- Pregnant or breastfeeding woman
- HIV co-infected patients requiring treatment with a protease inhibitor