Project 170718

Although effective medications to treat and prevent Tuberculosis (TB) have been available for over 60 years, TB remains the most important infectious cause of mortality among adults in the world. One of the cornerstones of control of this disease is detection and treatment of TB infection while it is still latent, or dormant. Nine months of daily Isoniazid (9INH) is very effective to treat latent infection, but this medication can cause serious, even fatal side effects, while the long duration of treatment makes it hard for patients to complete treatment, and increases cost. An alternate treatment, of four months daily Rifampin (4RIF) has been recommended, Since there is not much published information about this treatment, we have initiated a research program to evaluate 4RIF. We have conducted two studies with 963 patients in total to compare 4RIF with 9INH. The 4RIF treatment is safer, particularly for liver toxicity - which is important because this complication can be fatal. As well more subjects completed a full course of 4RIF, and this treatment costs less. We are now proposing a third phase to compare the effectiveness of the two regimens in preventing active TB. Clinics in Montreal, Toronto, Saskatoon, Edmonton and Vancouver will be involved, as well as clinics in West Africa, Australia, Brazil, Ecuador, Korea, and Saudi Arabia. We plan to enroll 5818 persons, who will be randomized (i.e. assigned by chance) to take either 9INH or 4RIF. We will continue to monitor safety closely, and measure costs of treatment and follow-up. All patients who agree to take part will be followed for over 2 years, to see if they develop active TB. If 4RIF is as effective as 9INH in preventing TB, this will be a major advance, because this treatment is safer, cheaper, and easier for patients to complete.

large-scale, international, randomized trial comparing two treatment regimens for latent TB infection