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Journal Article > Research

Four-month high-dose rifampicin regimens for pulmonary tuberculosis

Jindani A, Atwine D, Grint D, Bah B, Adams J, Ticona ER, Shrestha BR, Agizew T, Hamid SS, Jamil B, Byamukama A, Kananura K, Mugisha Taremwa I, Bonnet MMB, Camara LM, Bah-Sow OY, Bah KS, Bah NM, Sow MS, Ticona Huaroto CE, Mugruza Pineda R, Tandukar B, Raya BB, Shrestha N, Mathoma A, Mathebula-Modongo UP, Basotli J, Irfan M, Begum D, Muzammil A, Ahmed I, Hasan R, Burgos MV, Sultan F, Hassan MRA, Masood I, Robb C, Decker J, Grubnic S, Butcher PD, Witney A, Dhillon J, Munshi T, Fielding K, Harrison TS
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Abstract
BACKGROUND
Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens.

METHODS
We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200?mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800?mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first.

RESULTS
Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively.

CONCLUSIONS
Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis.
Countries
BotswanaGuineaNepalPakistanPeruUganda
Subject Area
tuberculosisantimicrobial resistance
DOI
10.1056/EVIDoa2300054
Published Date
01-Sep-2023
PubMed ID
31981713
Languages
English
Journal
NEJM Evidence
Volume / Issue / Pages
Volume 2, Issue 9, Pages 1-12
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