Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial.
BACKGROUND
Treatment of latent tuberculosis infection with isoniazid for 9 months is complicated by poor patient adherence and the need for close follow-up of side effects, especially hepatotoxicity. Shorter and safer regimens are needed.


OBJECTIVE
To compare the frequency of adverse events and treatment completion in 2 treatment regimens for latent tuberculosis infection.


METHODS
Multicenter, randomized, open-label trial.


METHODS
Tuberculosis clinics located in university hospitals in Canada, Brazil, and Saudi Arabia.


METHODS
847 patients without a contraindication for rifampin and requiring treatment for latent tuberculosis infection.


METHODS
Four months of daily rifampin therapy or 9 months of daily isoniazid therapy.


METHODS
Grade 3 to 4 drug-related adverse events resulting in drug discontinuation (primary outcome), and on-time treatment completion, grade 1 to 2 drug-related adverse events, and changes in liver enzymes and hematologic variables (secondary outcomes).


RESULTS
Seventeen of 422 participants who started isoniazid therapy developed grade 3 to 4 adverse events compared with 7 of 418 who started rifampin therapy (risk difference [rifampin minus isoniazid], -2.3% [95% CI, -5% to -0.1%]; P = 0.040). Grade 3 or 4 hepatitis occurred in 16 of 422 isoniazid recipients compared with 3 of 418 rifampin recipients (risk difference, -3.1% [CI, -5% to -1%]; P = 0.003). Grade 1 or 2 adverse events attributed to study drugs occurred with similar frequency. Asymptomatic reduction in platelet and leukocyte counts were more frequent in rifampin recipients. More patients completed rifampin treatment (78%) than isoniazid treatment (60%) (difference, 18% [CI, 12% to 24%]; P < 0.001]).


CONCLUSIONS
The study did not measure efficacy, and the open-label design may increase the chance of bias in ascertainment of adverse events.


CONCLUSIONS
Treatment of latent tuberculosis with 4 months of rifampin leads to fewer serious adverse events and better adherence than 9 months of isoniazid. These findings justify a large-scale trial to compare the efficacy of rifampin with that of isoniazid.
Menzies
Dick
D
Montreal Chest Institute, McGill University, Montreal, Quebec, Canada. dick.menzies@mcgill.ca
Long
Richard
R
Trajman
Anete
A
Dion
Marie-Josée
MJ
Yang
Jae
J
Al Jahdali
Hamdan
H
Memish
Ziad
Z
Khan
Kamran
K
Gardam
Michael
M
Hoeppner
Vernon
V
Benedetti
Andrea
A
Schwartzman
Kevin
K
D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects*; D008099:Liver / Q000201:enzymology; D008297:Male; D010349:Patient Compliance; D010352:Patient Dropouts; D011446:Prospective Studies; D012293:Rifampin / Q000009:adverse effects*; D000637:Transaminases / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
D000995:Antitubercular Agents; D000637:Transaminases; D007538:Isoniazid; D012293:Rifampin