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
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Published in |
Trials, November 2017
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DOI | 10.1186/s13063-017-2292-x |
Pubmed ID | |
Authors |
Tara C. Bouton, Patrick P. J. Phillips, Carole D. Mitnick, Charles A. Peloquin, Kathleen Eisenach, Ramonde F. Patientia, Leonid Lecca, Eduardo Gotuzzo, Neel R. Gandhi, Donna Butler, Andreas H. Diacon, Bruno Martel, Juan Santillan, Kathleen Robergeau Hunt, Dante Vargas, Florian von Groote-Bidlingmaier, Carlos Seas, Nancy Dianis, Antonio Moreno-Martinez, C. Robert Horsburgh |
Abstract |
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. 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. 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. ClinicalTrials.gov, NCT01918397 . Registered on 5 August 2013. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 99 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 11 | 11% |
Researcher | 11 | 11% |
Student > Master | 10 | 10% |
Student > Bachelor | 9 | 9% |
Other | 6 | 6% |
Other | 23 | 23% |
Unknown | 29 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 24 | 24% |
Nursing and Health Professions | 8 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 7% |
Biochemistry, Genetics and Molecular Biology | 6 | 6% |
Unspecified | 6 | 6% |
Other | 18 | 18% |
Unknown | 30 | 30% |