Grant: Operating Grant: Clinical Trials Projects - Indirect Costs

Tuberculosis (TB) causes death, severe illness, and long term disability in millions of persons globally each year. This could be avoided through TB preventive treatment (TPT), but only a small minority of persons who could benefit actually take this treatment. Current regimens are long, and can cause serious side effects, even deaths. This makes doctors and nurses reluctant to prescribe TPT, and many persons reluctant to take this treatment. Since TPT is given to otherwise healthy persons without any symptoms of TB, safety of this treatment is absolutely essential. We have shown that 4 months daily Rifampin (4R) is safer, better tolerated, and as effective as 9 months INH (9H), which it has now replaced as the standard TPT regimen in Canada. But 4 months is still long, and many people find it challenging to complete this. We have just completed a study of 1360 participants in which we found that Rifampin at double the standard dose was safe. At the same time other researchers have found that one month of INH and Rifapentine (1HP) is promising, and appears as safe as 9 months INH, but did not compare to a safer treatment like 4 months rifampin. There are other promising treatments, such as one month levofloxacin and rifapentine. In adults and children older than 4, who agree to participate, we will assess severe side effects that cause the drugs to be stopped, as well how many persons complete three different short treatments. We will also assess tolerability, defined as having symptoms that are not severe enough to stop the drug but are bothersome; and acceptability from interviews with participants. We will also measure blood concentrations of the study drugs. If a new TPT regimen meets all criteria - of being safe, well tolerated, and acceptable then a large scale study will be planned to assess how well this works, to prevent TB disease in persons with TB infection.