Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults
Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults
Data
2018
Autores
Menzies, D.
Adjobimey, M.
Ruslami, R.
Trajman, A.
Sow, O.
Kim, H.
Baah, J. Obeng
Marks, G.B.
Long, R.
Hoeppner, V.
Journal Title
Journal ISSN
Volume Title
Publisher
The New England Journal of Medicine
Resumo
BACKGROUND:
A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent
tuberculosis infection. However, the regimen has been associated with poor adherence
rates and with toxic effects.
METHODS:
In an open-label trial conducted in nine countries, we randomly assigned adults with
latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or
a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis
within 28 months after randomization. Noninferiority and potential superiority were
assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse
events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adju-
dicated by independent review panels.
RESULTS:
Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed
in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years
of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the
isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin
minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence inter-
val [CI], −0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100
person-years (95% CI, −0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis.
The upper boundaries of the 95% confidence interval for the rate differences of the
confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis
were less than the prespecified noninferiority margin of 0.75 percentage points in cu-
mulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The
difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7
to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days
(120% of the 4-month planned duration of the rifampin regimen) were −1.1 percentage
points (95% CI, −1.9 to −0.4) for all events and −1.2 percentage points (95% CI, −1.7 to
−0.7) for hepatotoxic events.
CONCLUSIONS:
The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid
for the prevention of active tuberculosis and was associated with a higher rate of treat-
ment completion and better safety. (Funded by the Canadian Institutes of Health Research
and the Australian National Health and Medical Research Council; ClinicalTrials.gov
number, NCT00931736.).
Description
Palavras-chave
Adolescent, Adult, Aged, Aged, 80 and over, Antibiotics, Antitubercular / administration & dosage*, Antibiotics, Antitubercular / adverse effects, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Isoniazid / administration & dosage*, Isoniazid / adverse effects, Latent Tuberculosis / drug therapy*, Male, Medication Adherence, Middle Aged, Rifampin / administration & dosage*, Rifampin / adverse effects.
Citação
Menzies D, Adjobimey M, Ruslami R, Trajman A, Sow O, Kim H, Obeng Baah J, Marks GB, Long R, Hoeppner V, Elwood K, Al-Jahdali H, Gninafon M, Apriani L, Koesoemadinata RC, Kritski A, Rolla V, Bah B, Camara A, Boakye I, Cook VJ, Goldberg H, Valiquette C, Hornby K, Dion MJ, Li PZ, Hill PC, Schwartzman K, Benedetti A. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. N Engl J Med. 2018 Aug 2;379(5):440-453. doi: 10.1056/NEJMoa1714283.