Novel Triple-dose Tuberculosis Retreatment Regimen
Novel Triple-dose Tuberculosis Retreatment Regimen
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).
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.

 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.
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

 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