RetourThree Phase III trials (i.e. REMoxTB, OFLOTUB and RIFAQUIN) failed to demonstrate non-inferiority of shorter regimens used to treat DS-TB (26-28). The recent Phase III trial Study 31 (1) assessed the safety and efficacy of two 4-month regimens for the treatment of DS-TB (29). Patients from 13 countries were recruited for this multicentre, open-label, three-arm non-inferiority RCT, which was carried out in adolescents and adults (aged ≥12 years) with smear and culture positive pulmonary DS-TB (29).
The 4-month rifapentine-moxifloxacin arm demonstrated non-inferiority when compared with the standard of care (the WHO-recommended 2HRZE/4HR regimen). The primary efficacy end-point of Study 31 was TB disease-free survival at 12 months after randomization, whereas the primary safety end-point was the proportion of participants with grade 3 or higher adverse events during the study’s drug treatment.
The proportion of patients who were cured was 84.5%, with 99.7% retention on treatment and 0.4% all-cause mortality recorded within 14 days of the end of treatment. Grade 3 or higher adverse events were noted in 18.8% of participants in the rifapentine-moxifloxacin arm compared with 19.3% in the standard 2HRZE/4HR regimen (29).
The slight difference in all-cause mortality and adverse events during treatment, and the slight increase in retention on treatment compared with the 6-month 2HRZE/4HR regimen allowed WHO to recommend this shorter regimen, as follows:
Patients aged 12 years or older with pulmonary DS-TB may receive a 4-month regimen of isoniazid, rifapentine, moxifloxacin and pyrazinamide. (2HPMZ/2HPM). (Conditional recommendation, moderate certainty of evidence) – new recommendation