Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis

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• Alternative Title:
  N Engl J Med
• Personal Author:
  Dorman, Susan E. ; Nahid, Payam ; Kurbatova, Ekaterina V. ; Phillips, Patrick P.J. ; Bryant, Kia ; Dooley, Kelly E. ; Engle, Melissa ; Goldberg, Stefan V. ; Phan, Ha T.T. ; Hakim, James ; Johnson, John L. ; Lourens, Madeleine ; Martinson, Neil A. ; Muzanyi, Grace ; Narunsky, Kim ; Nerette, Sandy ; Nguyen, Nhung V. ; Pham, Thuong H. ; Pierre, Samuel ; Purfield, Anne E. ; Samaneka, Wadzanai ; Savic, Radojka M. ; Sanne, Ian ; Scott, Nigel A. ; Shenje, Justin ; Sizemore, Erin ; Vernon, Andrew ; Waja, Ziyaad ; Weiner, Marc ; Swindells, Susan ; Chaisson, Richard E.
  More +
• Description:
  BACKGROUND ; Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis. ; METHODS ; In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months. ; RESULTS ; Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval CI, −2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, −1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points 95% CI, −0.6 to 6.6; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points 95% CI, 1.2 to 7.7). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group. ; CONCLUSIONS ; The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.)
• Subjects:
  • Adolescent
  • Adult
  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Child
  • Confidence Intervals
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
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• Source:
  N Engl J Med. 384(18):1705-1718
• Pubmed ID:
  33951360
• Pubmed Central ID:
  PMC8282329
• Document Type:
  Text
• Funding:
  UM1 AI068634/AI/NIAID NIH HHSUnited States/ ; UM1 AI069463/AI/NIAID NIH HHSUnited States/ ; UM1 AI106701/AI/NIAID NIH HHSUnited States/ ; UM1 AI068636/AI/NIAID NIH HHSUnited States/ ; UM1 AI068634, UM1 AI068636 and UM1 AI106701./National Institute of Allergy and Infectious Diseases/ ; 200-2009-32582, 200-2009-32593, 200-2009-32594, 20/CC/CDC HHSUnited States/
• Genre:
  Journal Article
• Volume:
  384
• Issue:
  18
• Download URL:
  https://stacks.cdc.gov/view/cdc/111315/cdc_111315_DS1.pdf
• File Type:
  [PDF - 1.01 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:0046cd4946d50df90b4ba1f44316e84e50546739ee67e2c78778ae4c69e0b04a78d2f6d3f1ec3dc84915f8d34cd2f84c8f976a62714f82bb5e5e9bf4d2816484