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

Mahamadou Bassirou Souleymane, Sani Kadri, Alberto Piubello, Achilleas Tsoumanis, Alphazazi Soumana, Hamidou Issa, Abdoulaziz Kabirou Amoussa, Armand Van Deun, Lutgarde Lynen, Bouke Catherine de Jong, Tom Decroo

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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; 6R 3H 3ZE) 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 6R 3H 3ZE 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/m 2. Drugrelated severe adverse events (AEs) (grade III-V) were significantly more frequent when 6R 3H 3ZE 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.

Original languageEnglish
JournalInternational Journal of Infectious Diseases
Pages (from-to)78-81
Number of pages4
Publication statusPublished - 2023


  • Adult
  • Antitubercular Agents/adverse effects
  • Drug Therapy, Combination
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Isoniazid/adverse effects
  • Male
  • Rifampin/adverse effects
  • Treatment Outcome
  • Tuberculosis/drug therapy

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