# Acceptability and safety of one versus three months of rifapentine and isoniazid to prevent tuberculosis in people exposed in the household or workplace in Brazil: The Ultra-Curto randomized controlled trial

## TL;DR

A study in Brazil compared one month of daily tuberculosis preventive therapy with three months of weekly therapy, finding both had high completion rates but similar safety profiles.

## Contribution

The study provides the first head-to-head comparison of 1HP and 3HP regimens in non-HIV individuals for tuberculosis prevention.

## Key findings

- Both 1HP and 3HP had high treatment completion rates (89.6% and 84.1%, respectively).
- 1HP had slightly higher rates of targeted safety events compared to 3HP.
- Neither regimen was found to be superior in terms of acceptability or safety.

## Abstract

Short-course tuberculosis preventive therapy with isoniazid and rifapentine (HP) is widely recommended, but the acceptability and safety of one month of daily HP (1HP) compared to three months of weekly HP (3HP) is uncertain. We compared treatment with these two regimens in people with a positive latent tuberculosis infection test and without HIV infection. We hypothesized that 1HP would have greater treatment completion and fewer targeted safety events than 3HP.

We conducted a Phase 4 randomized trial of 1HP versus 3HP in adolescents and adults without HIV infection with recent tuberculosis exposure and a positive latent tuberculosis infection test in two sites in Brazil. The primary outcomes were successful completion of >90% of medication as ascertained by self-report, pill counts, and pharmacologic monitoring, and safety. Treatment safety was defined as occurrence of Grade >2 targeted events or discontinuation of treatment for side effects. We randomized 500 individuals to 1HP (249) and 3HP (251); 193 males and 307 females, with a median age of 39 years. Treatment completion was 89.6% for 1HP recipients versus 84.1% for 3HP recipients (site-adjusted risk difference 5.2%, [95% CI: [−0.1%, 11.2%], p = 0.10). Targeted >Grade 2 adverse safety events or treatment discontinuation occurred in 16.1% of 1HP recipients and 10.4% of 3HP recipients (site-adjusted risk difference 6.1%, [95%CI: [−0.04%, 12.3%], p = 0.05). The proportions who discontinued treatment for any side effect were 7.2% for 1HP and 4.4% for 3HP. The risk difference for the primary safety outcome adjusted for site and baseline demographic and clinical covariates was 3.4% (95% CI [−2.3,9.1%], p = 0.24). The trial was not designed to ascertain efficacy.

Both 1HP and 3HP had high rates of treatment success. Participants assigned to 1HP had more targeted safety events, mostly low-grade. Neither regimen was superior to the other. These results will inform global guidelines for tuberculosis preventive therapy. NCT04703075 (clinicaltrials.gov).

Tuberculosis Preventive Therapy (TPT) is an important method for reducing the incidence of tuberculosis that previously required 6–9 months of treatment.

Two new shorter treatment regimens (1HP and 3HP) have been shown to be efficacious, but 1HP has only been studied in people with HIV infection and the safety of the regimens has not been compared in a head-to-head trial.

We performed a randomized clinical trial comparing treatment success, defined as completing >90% of medication, and safety of these two regimens in 500 adolescents and adults without HIV infection who had positive tests for TB infection after exposure to someone with active TB in their household or workplace.

We found that both 1HP and 3HP had high rates of treatment success and low rates of adverse safety effects.

This study of 1HP in people without HIV infection demonstrates that the regimen is safe and has high completion rates.

Both regimens had similar rates of completion and the 3HP regimen had slightly lower rates of adverse reactions.

These data show that both regimens can be used by clinicians and public health programs as options for TPT.

The study was not designed to determine whether either regimen was more effective than the other due to the small sample size.

In a multi-center, randomized controlled trial, Betina Durovni and colleagues assess the acceptability and safety of a short-course tuberculosis preventive therapy taken daily or weekly for different durations by persons recently exposed to tuberculosis. short version: In a randomized controlled trial, Betina Durovni and colleagues assess the acceptability and safety of a short-course tuberculosis preventive therapy for different durations.