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Comparative efficacy and acceptability of five anti-tubercular drugs in treatment of multidrug resistant tuberculosis: a network meta-analysis.

ABSTRACT: Multidrug resistant tuberculosis (MDR-TB) is a serious form of tuberculosis (TB). There is no recognized effective treatment for MDR-TB, although there are a number of publications that have reported positive results for MDR-TB. We performed a network meta-analysis to assess the efficacy and acceptability of potential antitubercular drugs. We conducted a network meta-analysis of randomized controlled clinical trials to compare the efficacy and acceptability of five antitubercular drugs, bedaquiline, delamanid, levofloxacin, metronidazole and moxifloxacin in the treatment of MDR-TB. We included eleven suitable trials from nine journal articles and six clinical trials from ClinicalTrials.gov, with data for 1472 participants. Bedaquiline (odds ratio [OR] 2.69, 95% CI 1.02-7.43), delamanid (OR 2.45, 95% CI 1.36-4.89) and moxifloxacin (OR 2.47, 95% CI 1.01, 7.31) were significantly more effective than placebo. For efficacy, the results indicated no statistical significance between each antitubercular drug. For acceptability, the results indicated no statistically significant difference between each compared intervention. There is insufficient evidence to suggest that any one of the five antitubercular drugs (bedaquiline, delamanid, levofloxacin, metronidazole and moxifloxacin) has superior efficacy compared to the others.

SUBMITTER: Wang H

PROVIDER: S-EPMC4416256 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Comparative efficacy and acceptability of five anti-tubercular drugs in treatment of multidrug resistant tuberculosis: a network meta-analysis.

Wang Huaidong H Zhang Xiaotian X Bai Yuanxiang Y Duan Zipeng Z Lin Yan Y Wang Guoqing G Li Fan F

Journal of clinical bioinformatics 20150428

Multidrug resistant tuberculosis (MDR-TB) is a serious form of tuberculosis (TB). There is no recognized effective treatment for MDR-TB, although there are a number of publications that have reported positive results for MDR-TB. We performed a network meta-analysis to assess the efficacy and acceptability of potential antitubercular drugs. We conducted a network meta-analysis of randomized controlled clinical trials to compare the efficacy and acceptability of five antitubercular drugs, bedaquil ...[more]

PMID: 25937888

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Project description:Mycobacterium tuberculosis develops spontaneous resistance mutants to virtually every drug in use. Courses of therapy select for these mutants and drug-resistant organisms emerge. The development of drug-resistant organisms has reached the point that drug resistance now threatens to undermine global success against tuberculosis (TB). New drugs are needed. The last new class of drugs specifically developed for treatment of TB was the rifamycins over 40 years ago. New funding sources and the development of product development partnerships have energized the TB drug development effort. There are now more TB drugs in development than at any time in the past. The first of these drugs to be developed and marketed was bedaquiline. Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport. This raises the exciting possibility that bedaquiline may be active against less metabolically active organisms. Drug-drug interactions between rifamycins and the cytochrome P450-3A system will limit bedaquiline's utility and create complexity in treatment regimens. In clinical trials, treatment with bedaquiline added to a background multidrug-resistant TB regimen was associated with earlier culture conversion and higher cure rates, but there were unexplained excess deaths in the bedaquiline arms of these trials. Food and Drug Administration approved bedaquiline for the treatment of multidrug-resistant TB when an effective treatment regimen cannot otherwise be provided. They required a black box warning about excess deaths and require that a phase III trial be completed. A planned Phase III trial is being reorganized. While bedaquiline is an exciting drug and marks a dramatic moment in the history of TB treatment, its ultimate place in the anti-TB drug armamentarium is unclear pending the Phase III trial and the development of other new drugs that are in the pipeline.

Dataset Information

Comparative efficacy and acceptability of five anti-tubercular drugs in treatment of multidrug resistant tuberculosis: a network meta-analysis.

Publications

Comparative efficacy and acceptability of five anti-tubercular drugs in treatment of multidrug resistant tuberculosis: a network meta-analysis.

Similar Datasets

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