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

doi:10.1016/j.ijid.2023.05.002

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

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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Abstract

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 language	English
Journal	International Journal of Infectious Diseases
Volume	133
Pages (from-to)	78-81
Number of pages	4
ISSN	1201-9712
DOIs	https://doi.org/10.1016/j.ijid.2023.05.002
Publication status	Published - 2023

Keywords

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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2023ijid0078Final published version, 327 KBLicence: CC BY-NC-ND

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Souleymane, M. B., Kadri, S., Piubello, A., Tsoumanis, A., Soumana, A., Issa, H., Amoussa, A. K., Van Deun, A., Lynen, L., de Jong, B. C., & Decroo, T. (2023). High rate of adverse drug reactions with a novel tuberculosis retreatment regimen combining triple-doses of both isoniazid and rifampicin. International Journal of Infectious Diseases, 133, 78-81. https://doi.org/10.1016/j.ijid.2023.05.002

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

abstract = "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.",

keywords = "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",

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

note = "FTX; DOAJ; (CC BY-NC-ND 4.0); Copyright {\textcopyright} 2023. Published by Elsevier Ltd.",

year = "2023",

doi = "10.1016/j.ijid.2023.05.002",

language = "English",

volume = "133",

pages = "78--81",

journal = "International Journal of Infectious Diseases",

issn = "1201-9712",

publisher = "Elsevier",

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Souleymane, MB, Kadri, S, Piubello, A, Tsoumanis, A, Soumana, A, Issa, H, Amoussa, AK, Van Deun, A, Lynen, L , de Jong, BC & Decroo, T 2023, 'High rate of adverse drug reactions with a novel tuberculosis retreatment regimen combining triple-doses of both isoniazid and rifampicin', International Journal of Infectious Diseases, vol. 133, pp. 78-81. https://doi.org/10.1016/j.ijid.2023.05.002

High rate of adverse drug reactions with a novel tuberculosis retreatment regimen combining triple-doses of both isoniazid and rifampicin. / Souleymane, Mahamadou Bassirou; Kadri, Sani; Piubello, Alberto et al.
In: International Journal of Infectious Diseases, Vol. 133, 2023, p. 78-81.

Research output: Contribution to journal › A1: Web of Science-article › peer-review

TY - JOUR

T1 - High rate of adverse drug reactions with a novel tuberculosis retreatment regimen combining triple-doses of both isoniazid and rifampicin

AU - Souleymane, Mahamadou Bassirou

AU - Kadri, Sani

AU - Piubello, Alberto

AU - Tsoumanis, Achilleas

AU - Soumana, Alphazazi

AU - Issa, Hamidou

AU - Amoussa, Abdoulaziz Kabirou

AU - Van Deun, Armand

AU - Lynen, Lutgarde

AU - de Jong, Bouke Catherine

AU - Decroo, Tom

PY - 2023

Y1 - 2023

N2 - 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.

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 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.

KW - Adult

KW - Antitubercular Agents/adverse effects

KW - Drug Therapy, Combination

KW - Drug-Related Side Effects and Adverse Reactions

KW - Female

KW - Humans

KW - Isoniazid/adverse effects

KW - Male

KW - Rifampin/adverse effects

KW - Treatment Outcome

KW - Tuberculosis/drug therapy

U2 - 10.1016/j.ijid.2023.05.002

DO - 10.1016/j.ijid.2023.05.002

M3 - A1: Web of Science-article

C2 - 37150352

SN - 1201-9712

VL - 133

SP - 78

EP - 81

JO - International Journal of Infectious Diseases

JF - International Journal of Infectious Diseases

ER -

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

Abstract

Keywords

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