• Dick Menzies, Richard Long, Anete Trajman, Marie-Josée Dion, Jae Yang, Hamdan Al Jahdali, Ziad Memish, Kamran Khan, Michael Gardam, Vernon Hoeppner, Andrea Benedetti, and Kevin Schwartzman.
• Montreal Chest Institute, McGill University, Montreal, Quebec, Canada. dick.menzies@mcgill.ca
• Ann. Intern. Med. 2008 Nov 18; 149 (10): 689-97.

BackgroundTreatment 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.ObjectiveTo compare the frequency of adverse events and treatment completion in 2 treatment regimens for latent tuberculosis infection.DesignMulticenter, randomized, open-label trial.SettingTuberculosis clinics located in university hospitals in Canada, Brazil, and Saudi Arabia.Patients847 patients without a contraindication for rifampin and requiring treatment for latent tuberculosis infection.InterventionFour months of daily rifampin therapy or 9 months of daily isoniazid therapy.MeasurementsGrade 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).ResultsSeventeen 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]).LimitationThe study did not measure efficacy, and the open-label design may increase the chance of bias in ascertainment of adverse events.ConclusionTreatment 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.

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