Randomized Clinical Trial to Improve TB Treatment

Enrollment began this month in Lima, Peru, in the first-ever, collaborative Partners In Health/Socios En Salud/Harvard Medical School/Brigham and Women's Hospital (PIH/SES/HMS/BWH) randomized clinical trial to improve tuberculosis (TB) treatment. This Phase II study will examine higher doses of a standard anti-TB drug, rifampin, to shorten the duration of TB therapy. The findings of the high-dose rifampin trial (known as HIRIF) are critical to the nine million people in the world who develop TB each year, nearly two million of whom die.

This study, and the capacity to implement it, is borne out of the longstanding partnership between PIH/SES [www.pih.org] and the Department of Global Health and Social Medicine (DGHSM), which began in the early 1990s. HIRIF, as part of the larger collaborative research and service endeavor, has enhanced important resources for those suffering from TB in Peru and elsewhere, including a world-class microbiology laboratory and centralized pharmacy.

HIRIF is funded by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health. It is a triple-blind, randomized trial with three treatment arms that will enroll 180 patients over the next year (see http://www.clinicaltrials.gov, NCT01408914). As a proof-of-concept study, the primary endpoint is pharmacokinetic. The study will estimate the relationship between blood concentrations of rifampin and dose. Secondary endpoints and substudies will explore the efficacy of increased concentrations of rifampin and novel methods for discerning the impact of treatment on important bacterial subpopulations. Safety is also important as cost and perceived dose-related toxicity derailed efforts to study higher doses of rifampin for TB in the 1980s. Study PI, Carole Mitnick, associate professor of global health and social medicine, considers this a distinct, social-justice building block in the effort to optimize TB treatment: for 50 years, doubts have persisted about the dose of rifampin prescribed for millions each year. These were never resolved, first because of the cost of the drug, later because of very limited resources devoted to research on TB, a disease of the poor. Now, the DGHSM and collaborators have a chance to right this long-standing wrong.