Bedaquiline, moxifloxacin, pretomanid, and pyrazinamide during the first 8 weeks of treatment of patients with drug-susceptible or drug-resistant pulmonary tuberculosis: a multicentre, open-label, partially randomised, phase 2b trial.
Antitubercular Agents
/ administration & dosage
Diarylquinolines
/ administration & dosage
Drug Administration Schedule
Drug Therapy, Combination
Humans
Moxifloxacin
/ administration & dosage
Nitroimidazoles
/ administration & dosage
Pyrazinamide
/ administration & dosage
Rifampin
/ administration & dosage
South Africa
Sputum
/ microbiology
Tanzania
Treatment Outcome
Tuberculosis, Multidrug-Resistant
/ drug therapy
Uganda
Journal
The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
11
12
2018
revised:
28
08
2019
accepted:
03
09
2019
pubmed:
17
11
2019
medline:
2
7
2020
entrez:
17
11
2019
Statut:
ppublish
Résumé
New anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis. In this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDRplus) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1-14 then 200 mg three times per week (B Between Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to B B TB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany.
Sections du résumé
BACKGROUND
New anti-tuberculosis regimens that are shorter, simpler, and less toxic than those that are currently available are needed as part of the global effort to address the tuberculosis epidemic. We aimed to investigate the bactericidal activity and safety profile of combinations of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide in the first 8 weeks of treatment of pulmonary tuberculosis.
METHODS
In this multicentre, open-label, partially randomised, phase 2b trial, we prospectively recruited patients with drug-susceptible or rifampicin-resistant pulmonary tuberculosis from seven sites in South Africa, two in Tanzania, and one in Uganda. Patients aged 18 years or older with sputum smear grade 1+ or higher were eligible for enrolment, and a molecular assay (GeneXpert or MTBDRplus) was used to confirm the diagnosis of tuberculosis and to distinguish between drug-susceptible and rifampicin-resistant tuberculosis. Patients who were HIV positive with a baseline CD4 cell count of less than 100 cells per uL were excluded. Patients with drug-susceptible tuberculosis were randomly assigned (1:1:1) using numbered treatment packs with sequential allocation by the pharmacist to receive 56 days of treatment with standard tuberculosis therapy (oral isoniazid, rifampicin, pyrazinamide, and ethambutol; HRZE), or pretomanid (oral 200 mg daily) and pyrazinamide (oral 1500 mg daily) with either oral bedaquiline 400 mg daily on days 1-14 then 200 mg three times per week (B
FINDINGS
Between Oct 24, 2014, and Dec 15, 2015, we enrolled 180 patients with drug-susceptible tuberculosis (59 were randomly assigned to B
INTERPRETATION
B
FUNDING
TB Alliance, UK Department for International Development, Bill & Melinda Gates Foundation, US Agency for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and the Federal Ministry for Education and Research of Germany.
Identifiants
pubmed: 31732485
pii: S2213-2600(19)30366-2
doi: 10.1016/S2213-2600(19)30366-2
pmc: PMC7641992
pii:
doi:
Substances chimiques
Antitubercular Agents
0
Diarylquinolines
0
Nitroimidazoles
0
pretomanid
0
Pyrazinamide
2KNI5N06TI
bedaquiline
78846I289Y
Moxifloxacin
U188XYD42P
Rifampin
VJT6J7R4TR
Banques de données
ClinicalTrials.gov
['NCT02193776']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1048-1058Subventions
Organisme : Medical Research Council
ID : MC_UU_12023/27
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
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