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A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis.

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Nunn, Andrew J, Phillips, Patrick P J, Meredith, Sarah K, Chiang, Chen-Yuan, Conradie, Francesca, Dalai, Doljinsuren, van Deun, Armand, Dat, Phan-Thuong, Lan, Ngoc, Master, Iqbal, Mebrahtu, Tesfamarium, Meressa, Daniel, Moodliar, Ronelle, Ngubane, Nosipho, Sanders, Karen, Squire, Bertie ORCID: https://orcid.org/0000-0001-7173-9038, Torrea, Gabriela, Tsogt, Bazarragchaa and Rusen, I D (2019) 'A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis.'. New England Journal of Medicine, Vol 380, pp. 1201-1213.

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Abstract

BACKGROUND

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 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 Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.).

Item Type: Article
Subjects: WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
WF Respiratory System > Tuberculosis > WF 250 Immunological aspects
WF Respiratory System > Tuberculosis > WF 310 Therapy
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1056/NEJMoa1811867
Depositing User: Stacy Murtagh
Date Deposited: 18 Mar 2019 11:38
Last Modified: 11 Apr 2019 14:23
URI: http://archive.lstmed.ac.uk/id/eprint/10399

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