Are higher rifampin doses for pulmonary TB more effective?
REPORTING FROM CROI 2018
BOSTON – Current daily doses of rifampin for treating pulmonary tuberculosis may be too low and could be safely increased, results of a randomized phase 2 study suggest.
“Back in the 1970s, rifampin was an expensive drug, and attempts to shorten TB therapy using higher but intermittent doses of rifampin were unsuccessful at that time because of increased toxicity. That line of inquiry was essentially dormant for 40 years,” said Gustavo Velásquez, MD, from Brigham & Women’s Hospital in Boston.
To get a better idea of optimal rifampin dosing for the treatment of pulmonary TB, Dr. Velásquez and his colleagues conducted the HIRIF (High-Dose Rifampin in Patients With TB) trial. The phase 2 study was designed to evaluate the pharmacokinetics, efficacy, and safety of higher daily rifampin doses for pulmonary TB.
They looked at the three parameters across three treatments arms: 10 mg/kg rifampin (the current standard of care), 15 mg/kg, or 20 mg/kg.
Patients in Peru were screened, enrolled, and randomized in cohorts of 60 patients each to one of the three specified dose levels, which they received either as additional rifampin tablets or placebo for the first 8 weeks of treatment, after which all patients were continued on rifampin 10 mg/kg to complete a 6-month regimen. All patients were followed for an additional 6 months to for assessment of TB recurrence.
Rifampin total doses ranged from as low as 300 mg for patients in the 30 kg-37 kg weight range, to as high as 1,500 mg for those weighing more than 70 kg.
