A trial of a shorter regimen for rifampin-resistant tuberculosis

Andrew J. Nunn, Patrick P.J. Phillips, Sarah K. Meredith, Chen Yuan Chiang, Francesca Conradie, Doljinsuren Dalai, Armand Van Deun, Phan Thu Ong Dat, Ngoc Lan, Iqbal Master, Tesfamarium Mebrahtu, Daniel Meressa, Ronelle Moodliar, Nosipho Ngubane, Karen Sanders, Stephen Bertel Squire, Gabriela Torrea, Bazarragchaa Tsogt, I. D. Rusen

研究成果: 雜誌貢獻文章

29 引文 (Scopus)

摘要

Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], −7.5 to 9.5) (P=0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, −10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P=0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONS In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current ControlledTrialsnumber,ISRCTN78372190;ClinicalTrials.govnumber,NCT02409290.).

原文英語
頁(從 - 到)1201-1213
頁數13
期刊New England Journal of Medicine
380
發行號13
DOIs
出版狀態已發佈 - 三月 28 2019

指紋

Fluoroquinolones
Aminoglycosides
Rifampin
Tuberculosis
United States Agency for International Development
Confidence Intervals
Social Adjustment
Multidrug-Resistant Tuberculosis
Bangladesh
Random Allocation
Mycobacterium tuberculosis
Population
Cohort Studies
HIV
Guidelines
Safety
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

引用此文

Nunn, A. J., Phillips, P. P. J., Meredith, S. K., Chiang, C. Y., Conradie, F., Dalai, D., ... Rusen, I. D. (2019). A trial of a shorter regimen for rifampin-resistant tuberculosis. New England Journal of Medicine, 380(13), 1201-1213. https://doi.org/10.1056/NEJMoa1811867

A trial of a shorter regimen for rifampin-resistant tuberculosis. / Nunn, Andrew J.; Phillips, Patrick P.J.; Meredith, Sarah K.; Chiang, Chen Yuan; Conradie, Francesca; Dalai, Doljinsuren; Van Deun, Armand; Dat, Phan Thu Ong; Lan, Ngoc; Master, Iqbal; Mebrahtu, Tesfamarium; Meressa, Daniel; Moodliar, Ronelle; Ngubane, Nosipho; Sanders, Karen; Squire, Stephen Bertel; Torrea, Gabriela; Tsogt, Bazarragchaa; Rusen, I. D.

於: New England Journal of Medicine, 卷 380, 編號 13, 28.03.2019, p. 1201-1213.

研究成果: 雜誌貢獻文章

Nunn, AJ, Phillips, PPJ, Meredith, SK, Chiang, CY, Conradie, F, Dalai, D, Van Deun, A, Dat, PTO, Lan, N, Master, I, Mebrahtu, T, Meressa, D, Moodliar, R, Ngubane, N, Sanders, K, Squire, SB, Torrea, G, Tsogt, B & Rusen, ID 2019, 'A trial of a shorter regimen for rifampin-resistant tuberculosis', New England Journal of Medicine, 卷 380, 編號 13, 頁 1201-1213. https://doi.org/10.1056/NEJMoa1811867
Nunn AJ, Phillips PPJ, Meredith SK, Chiang CY, Conradie F, Dalai D 等. A trial of a shorter regimen for rifampin-resistant tuberculosis. New England Journal of Medicine. 2019 3月 28;380(13):1201-1213. https://doi.org/10.1056/NEJMoa1811867
Nunn, Andrew J. ; Phillips, Patrick P.J. ; Meredith, Sarah K. ; Chiang, Chen Yuan ; Conradie, Francesca ; Dalai, Doljinsuren ; Van Deun, Armand ; Dat, Phan Thu Ong ; Lan, Ngoc ; Master, Iqbal ; Mebrahtu, Tesfamarium ; Meressa, Daniel ; Moodliar, Ronelle ; Ngubane, Nosipho ; Sanders, Karen ; Squire, Stephen Bertel ; Torrea, Gabriela ; Tsogt, Bazarragchaa ; Rusen, I. D. / A trial of a shorter regimen for rifampin-resistant tuberculosis. 於: New England Journal of Medicine. 2019 ; 卷 380, 編號 13. 頁 1201-1213.
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abstract = "Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95{\%} confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8{\%} of participants in the long-regimen group and in 78.8{\%} of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95{\%} confidence interval [CI], −7.5 to 9.5) (P=0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95{\%} CI, −10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4{\%} of participants in the long-regimen group and in 48.2{\%} in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0{\%} of participants in the short-regimen group, as compared with 6.4{\%} in the long-regimen group (P=0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5{\%} of participants in the short-regimen group and in 6.4{\%} in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3{\%} and 2.3{\%}, respectively. CONCLUSIONS In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current ControlledTrialsnumber,ISRCTN78372190;ClinicalTrials.govnumber,NCT02409290.).",
author = "Nunn, {Andrew J.} and Phillips, {Patrick P.J.} and Meredith, {Sarah K.} and Chiang, {Chen Yuan} and Francesca Conradie and Doljinsuren Dalai and {Van Deun}, Armand and Dat, {Phan Thu Ong} and Ngoc Lan and Iqbal Master and Tesfamarium Mebrahtu and Daniel Meressa and Ronelle Moodliar and Nosipho Ngubane and Karen Sanders and Squire, {Stephen Bertel} and Gabriela Torrea and Bazarragchaa Tsogt and Rusen, {I. D.}",
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pages = "1201--1213",
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TY - JOUR

T1 - A trial of a shorter regimen for rifampin-resistant tuberculosis

AU - Nunn, Andrew J.

AU - Phillips, Patrick P.J.

AU - Meredith, Sarah K.

AU - Chiang, Chen Yuan

AU - Conradie, Francesca

AU - Dalai, Doljinsuren

AU - Van Deun, Armand

AU - Dat, Phan Thu Ong

AU - Lan, Ngoc

AU - Master, Iqbal

AU - Mebrahtu, Tesfamarium

AU - Meressa, Daniel

AU - Moodliar, Ronelle

AU - Ngubane, Nosipho

AU - Sanders, Karen

AU - Squire, Stephen Bertel

AU - Torrea, Gabriela

AU - Tsogt, Bazarragchaa

AU - Rusen, I. D.

PY - 2019/3/28

Y1 - 2019/3/28

N2 - Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], −7.5 to 9.5) (P=0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, −10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P=0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONS In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current ControlledTrialsnumber,ISRCTN78372190;ClinicalTrials.govnumber,NCT02409290.).

AB - Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides. Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines. The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], −7.5 to 9.5) (P=0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, −10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P=0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONS In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current ControlledTrialsnumber,ISRCTN78372190;ClinicalTrials.govnumber,NCT02409290.).

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