High rate of adverse drug reactions with a novel tuberculosis re-treatment regimen combining triple doses of both isoniazid and rifampicin.

OBJECTIVES: High-dose rifampicin (R) and isoniazid (H) are known to be safe but were not yet combined in a single regimen. The primary objective of the TRIple-DOse RE-treatment (TRIDORE) study is to determine whether a 6-month firstline regimen with triple dose of both R and H (intervention arm; 6R3H3ZE) is non-inferior in terms of safety compared to a normal-dose regimen (6RHZE) in previously treated patients with R-susceptible (Rs) recurrent tuberculosis (TB). DESIGN/METHODS: TRIDORE is an ongoing pragmatic open-label multi-stage randomized clinical trial. RESULTS: Between March 2021 and February 2022, 127 consenting patients were randomly assigned to either the intervention or control arm: 62 and 65 were treated with 6R3H3ZE and 6RHZE, respectively. Of 127, 111 (87.4%) were male and the median age (interquartile range) was 37 (30-48) years. The median body mass index at enrollment was 18.1 (16.3-19.7) kg/m2. Drugrelated severe adverse events (AEs) (grade III-V) were significantly more frequent when 6R3H3ZE was used (5/62 vs 0/65, P = 0.03, difference weighted for site 8% [95% confidence interval: 1.0,14.3]). The Data and Safety Monitoring Board recommended publishing our interim safety data analysis. CONCLUSION: We show that the combination of triple-dose R with triple-dose H in a re-treatment regimen for patients with Rs-TB causes excess drug-related AEs.

[Epidemiological, clinical and evolutionary profile of patients with tuberculosis at the Regional Hospital of Maradi, Republic of the Niger]. / Profil épidémiologique, clinique et évolutif des patients tuberculeux au Centre Hospitalier Régional (CHR) de Maradi, République du Niger.

INTRODUCTION: This study aimed to describe the epidemiological, clinical and evolutionary profile of patients treated for tuberculosis at the Regional Hospital of Maradi. METHODS: We conducted a retrospective, descriptive and analytical study of data from the medical records of patients treated for tuberculosis from 1st January 2015 to 31st December 2017. RESULTS: A total of 595 patients were followed (406 men, 68.24%, and 189 women, 31.76%) with a prevalence of 27,71%. The average age of patients was 42.3 ranging from 13 months to 85 years; 70.5% of these patients were from urban areas. Merchants represented 36.9% of the cases. Bacterial test was positive in 64.7% of cases. Functional signs included: coughing (99.5%), fever (79.5%), and chest pain. Pulmonary tuberculosis represented 78.7% of cases. Therapy was effective in 81.28% of cases. HIV prevalence was 13.6%, lethality 10.42% (40.4% of patients died from TB/HIV co-infection). CONCLUSION: Tuberculosis is a scourge in low-income countries, with 10.42% of deaths. HIV/AIDS infection has negatively contributed to these deaths during the study period. The search for comorbidities in any patient with tuberculosis should be systematic in order to improve their global management.