Self-administered versus directly observed once-weekly isoniazid and rifapentine treatment of latent tuberculosis infection

Robert Belknap, David Holland, Pei Jean Feng, Joan Pau Millet, Joan A. Cayla, Neil A. Martinson, Alicia Wright, Michael P. Chen, Ruth N. Moro, Nigel A. Scott, Bert Arevalo, Jose M. Miro, Margarita E. Villarino, Marc H Weiner, Andrey S. Borisov

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Background: Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective: To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design: An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711) Setting: Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants: 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention: Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements: The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event- monitoring devices for self-administration. The main secondary outcome was adverse events. Results: Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the directobservation group, 74.0% (CI, 68.9% to 78.6%) in the selfadministration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration-with-reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups. Limitation: Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion: These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible. Primary Funding Source: Centers for Disease Control and Prevention.

Original languageEnglish (US)
Pages (from-to)689-697
Number of pages9
JournalAnnals of Internal Medicine
Volume167
Issue number10
DOIs
StatePublished - Nov 21 2017
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Belknap, R., Holland, D., Feng, P. J., Millet, J. P., Cayla, J. A., Martinson, N. A., Wright, A., Chen, M. P., Moro, R. N., Scott, N. A., Arevalo, B., Miro, J. M., Villarino, M. E., Weiner, M. H., & Borisov, A. S. (2017). Self-administered versus directly observed once-weekly isoniazid and rifapentine treatment of latent tuberculosis infection. Annals of Internal Medicine, 167(10), 689-697. https://doi.org/10.7326/M17-1150