High-dose rifampin may help shorten tuberculosis treatment
Higher doses of rifampin result in more rapid sputum sterilization and similar toxicity, a study has shown. These findings support the investigation of increased rifampin doses to shorten tuberculosis treatment.
To determine whether increased rifampin doses could shorten standard therapy for tuberculosis without increased toxicity, the investigators conducted a blinded, randomized, controlled phase II clinical trial involving 180 adults with new smear-positive pulmonary tuberculosis, susceptible to isoniazid and rifampin. Participants were randomized 1:1:1 to 10, 15 and 20 mg/kg/day of rifampin during the intensive phase.
The primary efficacy and safety endpoints were as follows: change in elimination rate of M. tuberculosis log10 colony forming units and frequency of grade ≥2 rifampin related adverse events (AEs). Efficacy by treatment arm and by primary (AUC/MIC) and secondary (AUC) pharmacokinetic exposure was also reported.
Differences of –0.011 (95 percent CI, –0.025 to 0.002; p=0.230) and –0.022 (–0.046 to –0.002; p=0.022) log10 colony forming units/mL/day were recorded in the modified intention-to-treat and per-protocol analyses, respectively, for every 5 mg/kg/day increase in rifampin dose. In the per-protocol group, elimination rate significantly increased with rifampin AUC0-6 (p=0.011) but not with AUC0-6/MIC99.9 (p=0.053).
Occurrence of grade ≥2 rifampin-related AEs showed similar frequency across the three treatment arms: 26 (43.3 percent), 31 (51.7 percent) and 23 (38.3 percent) participants in the 10, 15 and 20 mg/kg/day rifampin dose groups, respectively, had at least one AE (p=0.7092) up to 4 weeks after the intensive phase. In addition, 11 (6.1 percent) participants had treatment failure or disease recurrence.