Four months daily rifampicin vs. 3 months daily rifampicin/isoniazid for the treatment of tuberculosis infection in asylum seekers: a randomized controlled trial

Abstract

Objectives: Treatment of tuberculosis (TB) infection is a core intervention of the TB elimination strategy. The WHO recommends both 4 months of daily rifampicin (4R) and 3 months of daily isoniazid/rifampicin (3HR) for preventive therapy, but no trial directly compared the two regimens. We measured the completion rate and tolerability of 4R and 3HR for TB preventive therapy.

Methods: We conducted a prospective, open-label, randomized phase 4 superiority trial to demonstrate an increase of at least 15% in the completion rate of 4R over 3HR among asylum seekers in Italy. Asylum seekers were tested for TB infection by the Quantiferon Plus test and offered to participate in the study if infected. The primary outcome was treatment completion, measured by adherence to clinical visits and pill count. Unadjusted Kaplan-Meier curves were used to compare permanent interruptions in the two arms by days of treatment. Generalized linear model for the binomial family and logit link function was performed to determine factors associated with treatment completion.

Results: From June 2021 to July 2023, we randomized 113 individuals to 4R and 112 to 3HR. Treatment was completed by 88 subjects (77.9; 95% CI, 69.1-85.1) in the 4R arm and 85 (75.9; 95% CI, 66.9-83.5) in the 3HR arm (p 0.7). The risk ratio for completing treatment was 1.03 (95% CI, 0.89-1.18) in the 4R arm compared with the 3HR arm with a risk difference of 0.03 (95% CI, -0.09 to 0.13). Dropout rates due to side effects (25/113 in 4R vs. 27/112 in 3HR) and the overall rate of adverse events (47/113 in 4R vs. 36/112 in 3HR) were not statistically different in the two groups.

Discussion: 4R was not superior, in terms of completion rate, to 3HR for the treatment of TB infection among asylum seekers in Italy.

Trial registration number: EudraCT 2021-001438-20.

Keywords: Asylum seekers; Tuberculosis infection; Tuberculosis preventive therapy.