Bouton, TC;
Phillips, PPJ;
Mitnick, CD;
Peloquin, CA;
Eisenach, K;
Patientia, RF;
Lecca, L;
... Horsburgh, CR; + view all
(2017)
An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens: study protocol for a randomized controlled trial.
Trials
, 18
, Article 563. 10.1186/s13063-017-2292-x.
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Abstract
Background: Current guidelines for treatment of multidrug-resistant tuberculosis (MDR-TB) are largely based on expert opinion and observational data. Fluoroquinolones remain an essential part of MDR-TB treatment, but the optimal dose of fluoroquinolones as part of the regimen has not been defined. Methods/design: We designed a randomized, blinded, phase II trial in MDR-TB patients comparing across levofloxacin doses of 11, 14, 17 and 20 mg/kg/day, all within an optimized background regimen. We assess pharmacokinetics, efficacy, safety and tolerability of regimens containing each of these doses. The primary efficacy outcome is time to culture conversion over the first 6 months of treatment. The study aims to determine the area under the curve (AUC) of the levofloxacin serum concentration in the 24 hours after dosing divided by the minimal inhibitory concentration of the patient’s Mycobacterium tuberculosis isolate that inhibits > 90% of organisms (AUC/MIC) that maximizes efficacy and the AUC that maximizes safety and tolerability in the context of an MDR-TB treatment regimen. Discussion: Fluoroquinolones are an integral part of recommended MDR-TB regimens. Little is known about how to optimize dosing for efficacy while maintaining acceptable toxicity. This study will provide evidence to support revised dosing guidelines for the use of levofloxacin as part of combination regimens for treatment of MDR-TB. The novel methodology can be adapted to elucidate the effect of other single agents in multidrug antibiotic treatment regimens.
| Type: | Article |
|---|---|
| Title: | An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens: study protocol for a randomized controlled trial |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13063-017-2292-x |
| Publisher version: | http://doi.org/10.1186/s13063-017-2292-x |
| Language: | English |
| Additional information: | Copyright © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated |
| Keywords: | Multidrug resistant tuberculosis, Optimized background regimen, Fluoroquinolones, Levofloxacin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10041760 |
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