A Pragmatic Trial of a 6-Month Strategy for Rifampicin-Resistant Tuberculosis.

BACKGROUND

Safer, more effective treatment regimens for rifampicin-resistant tuberculosis are needed.

METHODS

We conducted a phase 3, open-label, pragmatic, randomized, controlled noninferiority trial in South Africa to assess a 6-month treatment strategy for pulmonary rifampicin-resistant tuberculosis. Participants with pulmonary rifampicin-resistant tuberculosis who were 6 years of age or older were randomly assigned to a regimen consisting of bedaquiline, linezolid, delamanid, and levofloxacin or clofazimine or both for 6 months (trial-strategy group) or the 9-month standard-of-care treatment regimen that was current in South Africa (control group). Persons who were pregnant or breastfeeding and those who had fluoroquinolone-resistant tuberculosis were included in the trial population. Treatment in both groups was adjusted on the basis of results of second-line drug susceptibility testing. The primary efficacy end point was a successful outcome (cure or completion of treatment) at the end of treatment and at 76 weeks after randomization. The noninferiority margin was 10 percentage points. The primary safety end point was an adverse event of grade 3 or higher.

RESULTS

Among the 432 persons who were screened, 403 underwent randomization; 203 were assigned to the trial-strategy group, and 200 to the control group. A successful outcome was observed in 174 of 202 participants (86.1%) in the trial-strategy group and in 172 of 200 (86.0%) in the control group. The adjusted risk difference was -0.2 percentage points (95% confidence interval [CI], -6.9 to 6.5; P = 0.001 for noninferiority). Adverse events of grade 3 or higher occurred during treatment in 63 of 202 participants (31.2%) in the trial-strategy group and in 74 of 200 (37.0%) in the control group; 10 participants in each group died.

CONCLUSIONS

Among participants in South Africa with rifampicin-resistant tuberculosis, the 6-month trial strategy was noninferior to the standard-of-care strategy with respect to a successful outcome. The safety profiles of the two strategies were similar. (Funded by the U.S. Agency for International Development and others; BEAT Tuberculosis ClinicalTrials.gov number, NCT04062201.).