Adverse Events with 4 Months of Rifampin Therapy or 9 Months of Isoniazid Therapy for Latent Tuberculosis Infection

Abstract

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. To compare the frequency of adverse events and treatment completion in 2 treatment regimens for latent tuberculosis infection. Multicenter, randomized, open-label trial. Tuberculosis clinics located in university hospitals in Canada, Brazil, and Saudi Arabia. 847 patients without a contraindication for rifampin and requiring treatment for latent tuberculosis infection. Four months of daily rifampin therapy or 9 months of daily isoniazid therapy. 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). 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##lt## 0.001]). The study did not measure efficacy, and the open-label design may increase the chance of bias in ascertainment of adverse events. 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.