Summary:
Tuberculosis (TB) causes death, severe illness, and long-term disability in millions of people 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 people reluctant to take this treatment. Since TPT is given to otherwise healthy persons without any symptoms of TB, the safety of this treatment is essential. We have shown that 4 months of daily Rifampin (4R) is safer, better tolerated, and as effective as 9 months of 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 completed a study of 1360 participants in which we found that Rifampin at double the standard dose was safe. There are other promising treatments, such as one month of INH and Rifapentine (1HP), or one month of levofloxacin and rifapentine, or an exciting new possibility - a combination of a vaccine adjuvant plus a short course of an anti-TB drug. In adults and children aged 5 and older, we will assess severe side effects that cause the drugs to be stopped, as well as how many people complete new TPT treatments. We will also assess tolerability, meaning bothersome symptoms that are not severe enough to stop the drug, acceptability from interviewing participants, concentrations in the blood of the study drugs, and costs. We will first compare two new TB preventive treatments – two months double-dose rifampin, and one month levofloxacin and rifapentine with the current standard of 4 months rifampin. After close to a year, we will re-assess and may drop one or both of these new treatments and add a new one. After this, we plan to assess how well TB is prevented by the TPT regimen that is safest, best tolerated, and accepted in this study.
Sex & Gender considerations:
Sex is a key determinant of TB infection as well as disease, so it will be considered carefully in design (to ensure inclusion of a representative sample of men and women), data gathering and analyses. In the analyses, planned secondary analyses will include separate estimates of effect, stratified by sex, and an examination of effect modification.
Gender will be considered as part of the qualitative component of this project. This component will explore how gender affects perceptions and understanding of TB and TB prevention, the experiences of participants with the health system during management of TB infection, including investigations prior to enrolment in the trial, as well as experiences as participants in the trial, plus treatment. This will also explore how gender affects the experience with each preventive treatment regimen (pill burden, duration, need for medical visits, and symptoms of side effects/adverse events), and how this may affect adherence and completion of each. Gender may also affect costs – from health system and societal perspectives. Items regarding gender identity will be included in the patient questionnaires. The relationship between gender identity and health system utilization, as well as costs borne by participants and their families, will be assessed in the analysis of this questionnaire.
