Conference Coverage

Are higher rifampin doses for pulmonary TB more effective?



The efficacy analysis was by modified intention to treat, excluding 6 patients who had insufficient log­10 colony-forming units (CFUs) of TB, and a per-protocol analysis excluding an additional 42 patients whose doses of rifampin were affected by three study halts for adverse events. After each halt and review by the data-safety monitoring board, the trial was allowed to resume, but because enrollment and experimental dosing also were suspended, patients in the 15- and 20-mg/kg arms received 10 mg/kg during the 2-5 week halts. The number of patients in the 10-, 15-, and 20-mg/kg doses included in the per-protocol analysis were 56, 38, and 38, respectively,

Pharmacokinetic evidence from this study, previously published, showed that the median maximum drug concentration (Cmax) in serum in the experimental arms reached the lower end of the targeted range of 8 mcg/mL or greater, whereas the median in the standard-of-care arm was 6.2 mcg/mL. Only 33% of patients in the 10-mg/kg arm reached the minimum 8-mcg/mL level, Dr. Velásquez noted, vs. 72% and 81% of patients in the 15- and 20-mg/kg doses, respectively.

In the modified intention-to-treat population, for every 5-mg/kg increase in rifampin dose, there was a nonsignificant trend toward faster decline in TB CFUs in sputum. Similarly, for every 1-log increase in rifampin AUC/MIC, there was a trend, albeit nonsignificant, toward faster decline.

However, in patients in the per-protocol analysis, every 5-mg/kg dose increase and 1-log increase in rifampin AUC was associated with significantly faster declines in CFUs (P = .022 and .011, respectively).


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