Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin: a study protocol of a phase II clinical trial (HighShort-RP).
adverse events
clinical pharmacology
clinical trials
tuberculosis
Journal
BMJ open
ISSN: 2044-6055
Titre abrégé: BMJ Open
Pays: England
ID NLM: 101552874
Informations de publication
Date de publication:
10 03 2022
10 03 2022
Historique:
entrez:
11
3
2022
pubmed:
12
3
2022
medline:
28
4
2022
Statut:
epublish
Résumé
Increased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen. Adult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (C The study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal. NCT04694586.
Identifiants
pubmed: 35273049
pii: bmjopen-2021-054788
doi: 10.1136/bmjopen-2021-054788
pmc: PMC8915351
doi:
Substances chimiques
Antitubercular Agents
0
Pyrazinamide
2KNI5N06TI
Isoniazid
V83O1VOZ8L
Rifampin
VJT6J7R4TR
Banques de données
ClinicalTrials.gov
['NCT04694586']
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e054788Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Clin Infect Dis. 2009 Jun 15;48(12):1685-94
pubmed: 19432554
J Antimicrob Chemother. 2013 Sep;68(9):2066-73
pubmed: 23657802
Drugs. 2014 Jun;74(8):839-54
pubmed: 24846578
Antimicrob Agents Chemother. 2017 Oct 24;61(11):
pubmed: 28827417
J Antimicrob Chemother. 2018 Oct 1;73(10):2838-2845
pubmed: 30124844
BMJ. 2013 Jan 08;346:e7586
pubmed: 23303884
Ann Intern Med. 2013 Feb 5;158(3):200-7
pubmed: 23295957
J Biomed Inform. 2019 Jul;95:103208
pubmed: 31078660
Am J Respir Crit Care Med. 2015 May 1;191(9):1058-65
pubmed: 25654354
Eur Respir J. 2021 Jul 20;58(1):
pubmed: 33542052
Scand J Infect Dis. 2013 Nov;45(11):825-36
pubmed: 24041274
J Biomed Inform. 2009 Apr;42(2):377-81
pubmed: 18929686
Int J Tuberc Lung Dis. 1999 Oct;3(10 Suppl 2):S231-79
pubmed: 10529902
Lancet. 2012 Sep 15;380(9846):986-93
pubmed: 22828481
Clin Pharmacokinet. 2021 Jun;60(6):685-710
pubmed: 33674941
N Engl J Med. 2021 May 6;384(18):1705-1718
pubmed: 33951360
J Infect Dis. 2018 Aug 14;218(6):991-999
pubmed: 29718390
Clin Microbiol Infect. 2020 Nov;26(11):1488-1492
pubmed: 32750539
Am J Respir Crit Care Med. 2003 May 15;167(10):1348-54
pubmed: 12519740
N Engl J Med. 2014 Oct 23;371(17):1599-608
pubmed: 25337749
Clin Microbiol Infect. 2015 Feb;21(2):148.e5-7
pubmed: 25640156
Clin Infect Dis. 2018 Jun 18;67(1):34-41
pubmed: 29917079
Tubercle. 1978 Mar;59(1):13-32
pubmed: 345572
PLoS One. 2013 Jul 03;8(7):e67030
pubmed: 23843980
Ther Drug Monit. 1997 Dec;19(6):669-74
pubmed: 9421109
Am Rev Respir Dis. 1978 Aug;118(2):219-28
pubmed: 100029
Br J Clin Pharmacol. 2019 Oct;85(10):2341-2350
pubmed: 31269277
Clin Pharmacol Ther. 2018 Apr;103(4):674-683
pubmed: 28653479
Tubercle. 1981 Jun;62(2):95-102
pubmed: 7029838
Lancet Microbe. 2020 Jun;1(2):e84-e92
pubmed: 33834177
Nat Med. 2018 Nov;24(11):1708-1715
pubmed: 30397355
Lancet Infect Dis. 2017 Jan;17(1):39-49
pubmed: 28100438
Lancet. 1972 May 20;1(7760):1079-85
pubmed: 4112569
N Engl J Med. 2014 Oct 23;371(17):1588-98
pubmed: 25337748
Anal Bioanal Chem. 2013 Jul;405(19):6323-35
pubmed: 23719934
Int J Tuberc Lung Dis. 2020 Jan 1;24(1):48-64
pubmed: 32005307
N Engl J Med. 2014 Oct 23;371(17):1577-87
pubmed: 25196020
J Infect Dis. 2013 Nov 1;208(9):1464-73
pubmed: 23901086
Antimicrob Agents Chemother. 2010 Jul;54(7):2847-54
pubmed: 20439617
Thorax. 2020 Jul;75(7):606-608
pubmed: 32354738
Eur Respir J. 2021 Jul 8;58(1):
pubmed: 33542056
Microbiol Spectr. 2014 Aug;2(4):MGM2-0023-2013
pubmed: 26104205
Am J Respir Crit Care Med. 2018 Sep 1;198(5):657-666
pubmed: 29954183
Antimicrob Agents Chemother. 2012 Nov;56(11):5442-9
pubmed: 22777045
Clin Infect Dis. 2017 May 15;64(10):1350-1359
pubmed: 28205671
Eur Respir J. 2019 Dec 19;54(6):
pubmed: 31601711
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Aug 15;878(24):2286-91
pubmed: 20663720