An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens: study protocol for a randomized controlled trial
| Autor: | Eduardo Gotuzzo, Bruno Martel, R. F. Patientia, Florian von Groote-Bidlingmaier, Kathleen D. Eisenach, Nancy Dianis, Carlos Seas, Andreas H. Diacon, Charles A. Peloquin, Patrick P. J. Phillips, Carole D. Mitnick, Antonio Moreno-Martinez, Donna Butler, Neel R. Gandhi, Leonid Lecca, Juan Santillan, Dante Vargas, Kathleen Robergeau Hunt, C. Robert Horsburgh, Tara C. Bouton |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Comparative Effectiveness Research Time Factors Multidrug resistant tuberculosis Drug Resistance Antitubercular Agents Medicine (miscellaneous) Levofloxacin Cardiorespiratory Medicine and Haematology law.invention Study Protocol 0302 clinical medicine Randomized controlled trial Clinical Protocols law Drug Resistance Multiple Bacterial Tuberculosis Multidrug-Resistant Culture conversion Pharmacology (medical) 030212 general & internal medicine Optimized background regimen lcsh:R5-920 Tuberculosis Multidrug-Resistant/diagnosis/drug therapy/microbiology Bacterial Area under the curve Pulmonary Multidrug-Resistant 3. Good health Infectious Diseases Treatment Outcome Tolerability Research Design 6.1 Pharmaceuticals Tuberculosis Pulmonary/diagnosis/drug therapy/microbiology Combination HIV/AIDS Drug Therapy Combination lcsh:Medicine (General) Infection Multiple medicine.drug Fluoroquinolones medicine.medical_specialty Clinical Trials and Supportive Activities Clinical Sciences 030106 microbiology Context (language use) Microbial Sensitivity Tests Drug Administration Schedule Vaccine Related 03 medical and health sciences Rare Diseases Drug Therapy Clinical Research Biodefense General & Internal Medicine Internal medicine medicine Tuberculosis Humans purl.org/pe-repo/ocde/ford#3.01.05 [https] Dosing Tuberculosis Pulmonary business.industry Prevention Mycobacterium tuberculosis/drug effects Evaluation of treatments and therapeutic interventions Mycobacterium tuberculosis Surgery Regimen Orphan Drug Emerging Infectious Diseases Good Health and Well Being Cardiovascular System & Hematology Antitubercular Agents/administration & dosage/adverse effects/pharmacokinetics Levofloxacin/administration & dosage/adverse effects/pharmacokinetics Antimicrobial Resistance business |
| Zdroj: | Trials Trials, vol 18, iss 1 Trials, Vol 18, Iss 1, Pp 1-8 (2017) |
| ISSN: | 1745-6215 0191-8397 |
| Popis: | 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. Trial registration ClinicalTrials.gov, NCT01918397. Registered on 5 August 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2292-x) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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