PMID- 37150352
OWN - NLM
STAT- MEDLINE
DCOM- 20230609
LR  - 20230609
IS  - 1878-3511 (Electronic)
IS  - 1201-9712 (Linking)
VI  - 133
DP  - 2023 Aug
TI  - High rate of adverse drug reactions with a novel tuberculosis re-treatment 
      regimen combining triple doses of both isoniazid and rifampicin.
PG  - 78-81
LID - S1201-9712(23)00550-7 [pii]
LID - 10.1016/j.ijid.2023.05.002 [doi]
AB  - 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(3)H(3)ZE) 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(3)H(3)ZE 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(3)H(3)ZE 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.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Souleymane, Mahamadou Bassirou
AU  - Souleymane MB
AD  - Damien Foundation, Niamey, Niamey, Niger. Electronic address: 
      bachirsoul@gmail.com.
FAU - Kadri, Sani
AU  - Kadri S
AD  - National Hospital of Niamey, Niamey, Niger.
FAU - Piubello, Alberto
AU  - Piubello A
AD  - Damien Foundation, Brussels, Belgium.
FAU - Tsoumanis, Achilleas
AU  - Tsoumanis A
AD  - Institute of Tropical Medicine, Clinical Trials Unit, Antwerp, Belgium.
FAU - Soumana, Alphazazi
AU  - Soumana A
AD  - Programme National de Lutte contre la Tuberculose, Coordination nationale, 
      Niamey, Niger.
FAU - Issa, Hamidou
AU  - Issa H
AD  - University of Zinder, Faculty of Health Sciences, Zinder, Niger.
FAU - Amoussa, Abdoulaziz Kabirou
AU  - Amoussa AK
AD  - Centre Hospitalier regional de Maradi, CAT, Maradi, Niger.
FAU - Van Deun, Armand
AU  - Van Deun A
AD  - Independent Consultant, Leuven, Belgium.
FAU - Lynen, Lutgarde
AU  - Lynen L
AD  - Institute of Tropical Medicine, TB-HIV Unit, Antwerp, Belgium.
FAU - de Jong, Bouke Catherine
AU  - de Jong BC
AD  - Institute of Tropical Medicine, Unit of Mycobacteriology, Antwerp, Belgium.
FAU - Decroo, Tom
AU  - Decroo T
AD  - Institute of Tropical Medicine, TB-HIV Unit, Antwerp, Belgium.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20230505
PL  - Canada
TA  - Int J Infect Dis
JT  - International journal of infectious diseases : IJID : official publication of the 
      International Society for Infectious Diseases
JID - 9610933
RN  - VJT6J7R4TR (Rifampin)
RN  - V83O1VOZ8L (Isoniazid)
RN  - 0 (Antitubercular Agents)
SB  - IM
MH  - Humans
MH  - Male
MH  - Adult
MH  - Female
MH  - Rifampin/adverse effects
MH  - Isoniazid/adverse effects
MH  - Antitubercular Agents/adverse effects
MH  - Drug Therapy, Combination
MH  - *Tuberculosis/drug therapy
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Adverse drug reactions
OT  - High isoniazid
OT  - High rifampicin
COIS- Declarations of competing interest The authors have no competing interests to 
      declare.
EDAT- 2023/05/08 00:41
MHDA- 2023/06/09 06:42
CRDT- 2023/05/07 19:26
PHST- 2023/03/01 00:00 [received]
PHST- 2023/04/20 00:00 [revised]
PHST- 2023/05/02 00:00 [accepted]
PHST- 2023/06/09 06:42 [medline]
PHST- 2023/05/08 00:41 [pubmed]
PHST- 2023/05/07 19:26 [entrez]
AID - S1201-9712(23)00550-7 [pii]
AID - 10.1016/j.ijid.2023.05.002 [doi]
PST - ppublish
SO  - Int J Infect Dis. 2023 Aug;133:78-81. doi: 10.1016/j.ijid.2023.05.002. Epub 2023 
      May 5.