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An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens: study protocol for a randomized controlled trial

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dc.contributor.author Bouton, Tara C.
dc.contributor.author Phillips, Patrick P. J.
dc.contributor.author Mitnick, Carole D.
dc.contributor.author Peloquin, Charles A.
dc.contributor.author Eisenach, Kathleen
dc.contributor.author Patientia, Ramonde F.
dc.contributor.author Lecca, Leonid
dc.contributor.author Gotuzzo Herencia, José Eduardo
dc.contributor.author Gandhi, Neel R.
dc.contributor.author Butler, Donna
dc.contributor.author Diacon, Andreas H.
dc.contributor.author Martel, Bruno
dc.contributor.author Santillan, Juan
dc.contributor.author Hunt, Kathleen Robergeau
dc.contributor.author Vargas, Dante
dc.contributor.author von Groote-Bidlingmaier, Florian
dc.contributor.author Seas Ramos, Carlos Rafael
dc.contributor.author Dianis, Nancy
dc.contributor.author Moreno-Martinez, Antonio
dc.contributor.author Horsburgh, C. Robert
dc.date.accessioned 2019-01-25T16:59:36Z
dc.date.available 2019-01-25T16:59:36Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4870
dc.description.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. en_US
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartofseries Trials
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Drug Resistance, Multiple, Bacterial en_US
dc.subject Antitubercular Agents/administration & dosage/adverse effects/pharmacokinetics en_US
dc.subject Clinical Protocols en_US
dc.subject Drug Administration Schedule en_US
dc.subject Drug Therapy, Combination en_US
dc.subject Fluoroquinolones en_US
dc.subject Humans en_US
dc.subject Levofloxacin en_US
dc.subject Levofloxacin/administration & dosage/adverse effects/pharmacokinetics en_US
dc.subject Microbial Sensitivity Tests en_US
dc.subject Multidrug resistant tuberculosis en_US
dc.subject Mycobacterium tuberculosis/drug effects en_US
dc.subject Optimized background regimen en_US
dc.subject Research Design en_US
dc.subject Time Factors en_US
dc.subject Treatment Outcome en_US
dc.subject Tuberculosis, Multidrug-Resistant/diagnosis/drug therapy/microbiology en_US
dc.subject Tuberculosis, Pulmonary/diagnosis/drug therapy/microbiology en_US
dc.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 en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1186/s13063-017-2292-x
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05
dc.relation.issn 1745-6215


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