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dc.contributor.authorGillespie, Stephen H.
dc.contributor.authorCrook, Angela M.
dc.contributor.authorMcHugh, Timothy D.
dc.contributor.authorMendel, Carl M.
dc.contributor.authorMeredith, Sarah K.
dc.contributor.authorMurray, Stephen R.
dc.contributor.authorPappas, Frances
dc.contributor.authorPhillips, Patrick P.J.
dc.contributor.authorNunn, Andrew J.
dc.contributor.authorfor the REMoxTB Consortium
dc.date.accessioned2015-03-07T00:01:34Z
dc.date.available2015-03-07T00:01:34Z
dc.date.issued2014-10-23
dc.identifier.citationGillespie , S H , Crook , A M , McHugh , T D , Mendel , C M , Meredith , S K , Murray , S R , Pappas , F , Phillips , P P J , Nunn , A J & for the REMoxTB Consortium 2014 , ' Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis ' , New England Journal of Medicine , vol. 371 , no. 17 , pp. 1577-1587 . https://doi.org/10.1056/NEJMoa1407426en
dc.identifier.issn0028-4793
dc.identifier.otherPURE: 147208418
dc.identifier.otherPURE UUID: 96f1f5d7-f986-4949-8aa2-ce814da4e30c
dc.identifier.otherBibtex: urn:1185a7a37968db08f4c89afb08fb9184
dc.identifier.otherPubMed: 25196020
dc.identifier.otherScopus: 84908126151
dc.identifier.otherORCID: /0000-0001-6537-7712/work/39477830
dc.identifier.otherWOS: 000343648500006
dc.identifier.urihttp://hdl.handle.net/10023/6192
dc.descriptionSupported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.en
dc.description.abstractBackground: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofNew England Journal of Medicineen
dc.rightsFrom The New England Journal of Medicine, Stephen H. Gillespie, Angela M. Crook, Timothy D. McHugh, Carl M. Mendel, Sarah K. Meredith, Stephen R. Murray, Frances Pappas, Patrick P.J. Phillips, and Andrew J. Nunn. Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis, Copyright © 2014 Massachusetts Medical Society. Reprinted with permission.en
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccRA0421en
dc.titleFour-month moxifloxacin-based regimens for drug-sensitive tuberculosisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Global Health Implementation Groupen
dc.contributor.institutionUniversity of St Andrews.Gillespie Groupen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Infection Groupen
dc.identifier.doihttps://doi.org/10.1056/NEJMoa1407426
dc.description.statusPeer revieweden
dc.date.embargoedUntil2015-03-07


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