Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial.

Abstract

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.

DESIGN:

Multicenter, randomized, open-label trial.

SETTING:

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

PATIENTS:

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

INTERVENTION:

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

MEASUREMENTS:

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]).

LIMITATION:

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

CONCLUSION:

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.

• Authors: Dick Menzies, Richard Long, Anete Trajman, Marie-Josée Dion, Jae Yang, Hamdan Al Jahdali, Ziad Memish, Kamran Khan, Michael Gardam, Vernon Hoeppner, Andrea Benedetti, Kevin Schwartzman
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 149 Issue 10 Pg. 689-97 (Nov 18 2008) ISSN: 1539-3704 [Electronic] United States
• PMID: 19017587 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antitubercular Agents
• Transaminases
• Isoniazid
• Rifampin

Topics

• Adolescent
• Adult
• Antitubercular Agents (adverse effects)
• Chemical and Drug Induced Liver Injury (enzymology, etiology)
• Drug Administration Schedule
• Female
• Humans
• Isoniazid (adverse effects)
• Liver (enzymology)
• Male
• Patient Compliance
• Patient Dropouts
• Prospective Studies
• Rifampin (adverse effects)
• Transaminases (metabolism)
• Tuberculosis (drug therapy)
• Young Adult