Prospective evaluation of improving fluoroquinolone exposure using centralised therapeutic drug monitoring (TDM) in patients with tuberculosis (PERFECT): a study protocol of a prospective multicentre cohort study.
clinical pharmacology
infectious diseases
organisation of health services
tuberculosis
Journal
BMJ open
ISSN: 2044-6055
Titre abrégé: BMJ Open
Pays: England
ID NLM: 101552874
Informations de publication
Date de publication:
16 06 2020
16 06 2020
Historique:
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
12
2
2021
Statut:
epublish
Résumé
Global multidrug-resistant tuberculosis (MDR-TB) treatment success rates remain suboptimal. Highly active WHO group A drugs moxifloxacin and levofloxacin show intraindividual and interindividual pharmacokinetic variability which can cause low drug exposure. Therefore, therapeutic drug monitoring (TDM) of fluoroquinolones is recommended to personalise the drug dosage, aiming to prevent the development of drug resistance and optimise treatment. However, TDM is considered laborious and expensive, and the clinical benefit in MDR-TB has not been extensively studied. This observational multicentre study aims to determine the feasibility of centralised TDM and to investigate the impact of fluoroquinolone TDM on sputum conversion rates in patients with MDR-TB compared with historical controls. Patients aged 18 years or older with sputum smear and culture-positive pulmonary MDR-TB will be eligible for inclusion. Patients receiving TDM using a limited sampling strategy (t=0 and t=5 hours) will be matched to historical controls without TDM in a 1:2 ratio. Sample analysis and dosing advice will be performed in a centralised laboratory. Centralised TDM will be considered feasible if >80% of the dosing recommendations are returned within 7 days after sampling and 100% within 14 days. The number of patients who are sputum smear and culture-negative after 2 months of treatment will be determined in the prospective TDM group and will be compared with the control group without TDM to determine the impact of TDM. Ethical clearance was obtained by the ethical review committees of the 10 participating hospitals according to local procedures or is pending (online supplementary file 1). Patients will be included after obtaining written informed consent. We aim to publish the study results in a peer-reviewed journal. ClinicalTrials.gov Registry (NCT03409315).
Identifiants
pubmed: 32554740
pii: bmjopen-2019-035350
doi: 10.1136/bmjopen-2019-035350
pmc: PMC7304807
doi:
Substances chimiques
Anti-Bacterial Agents
0
Fluoroquinolones
0
Banques de données
ClinicalTrials.gov
['NCT03409315']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e035350Subventions
Organisme : NIAID NIH HHS
ID : U01 AI115594
Pays : United States
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Anal Bioanal Chem. 2009 Mar;393(5):1499-504
pubmed: 18791707
Clin Infect Dis. 2015 Mar 15;60(6):969-70
pubmed: 25527653
Eur Respir J. 2018 May 17;51(5):
pubmed: 29678945
Antimicrob Agents Chemother. 2019 Jun 24;63(7):
pubmed: 31010868
Eur Respir J. 2012 Dec;40(6):1430-42
pubmed: 22496332
Lancet. 2019 Sep 14;394(10202):953-966
pubmed: 31526739
Int J Tuberc Lung Dis. 2015 Apr;19(4):406-12
pubmed: 25859995
Clin Pharmacokinet. 2010 Aug;49(8):559-65
pubmed: 20608757
J Antimicrob Chemother. 2016 Oct;71(10):2691-703
pubmed: 27231277
Antimicrob Agents Chemother. 2016 Sep 23;60(10):5928-32
pubmed: 27458224
Eur Respir J. 2014 Jul;44(1):23-63
pubmed: 24659544
Int J Infect Dis. 2018 Mar;68:18-23
pubmed: 29253711
Eur Respir J. 2016 Feb;47(2):680-2
pubmed: 26828056
Eur Respir J. 2011 Oct;38(4):888-94
pubmed: 21310881
Clin Infect Dis. 2017 Jan 1;64(1):104-105
pubmed: 27789609
Clin Infect Dis. 2019 Mar 5;68(6):1065-1066
pubmed: 30219826
J Anal Toxicol. 2010 Apr;34(3):135-41
pubmed: 20406537
Eur Respir J. 2017 Apr 26;49(4):
pubmed: 28446561
Eur Respir J. 2017 May 21;49(5):
pubmed: 28529205
Microbiol Spectr. 2017 Jan;5(1):
pubmed: 28084209
Antimicrob Agents Chemother. 2017 Jul 25;61(8):
pubmed: 28507117
Clin Infect Dis. 2020 Apr 10;70(8):1774-1780
pubmed: 31560376
Health Hum Rights. 2016 Jun;18(1):85-102
pubmed: 27781001
Clin Infect Dis. 2018 Aug 16;67(5):708-716
pubmed: 29514175
Antimicrob Agents Chemother. 2018 Nov 26;62(12):
pubmed: 30373800
Lancet. 2018 Sep 8;392(10150):821-834
pubmed: 30215381
Antimicrob Agents Chemother. 2019 Apr 25;63(5):
pubmed: 30782999
Clin Infect Dis. 2018 Nov 28;67(suppl_3):S293-S302
pubmed: 30496461
JAMA. 2013 Nov 27;310(20):2191-4
pubmed: 24141714
Clin Infect Dis. 2016 Oct 1;63(7):e147-e195
pubmed: 27516382
Lancet Infect Dis. 2017 Sep;17(9):898
pubmed: 28845791
Eur Respir J. 2016 Apr;47(4):1288-90
pubmed: 27037319
Clin Infect Dis. 2018 Nov 28;67(suppl_3):S327-S335
pubmed: 30496467
J Infect Dis. 2013 Nov 1;208(9):1464-73
pubmed: 23901086
Eur Respir J. 2019 Jun 5;53(6):
pubmed: 31023852
Expert Opin Drug Metab Toxicol. 2016 May;12(5):509-21
pubmed: 26950189
J Infect Dis. 2004 Nov 1;190(9):1642-51
pubmed: 15478070
J Infect Dis. 2011 Dec 15;204(12):1951-9
pubmed: 22021624
Int J Tuberc Lung Dis. 2019 Jun 1;23(6):645-662
pubmed: 31315696
Eur Respir J. 2016 Jun;47(6):1867-9
pubmed: 26989104
BMC Infect Dis. 2017 Feb 6;17(1):125
pubmed: 28166721