Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection

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• Alternative Title:
  Ann Intern Med
• Personal Author:
  Belknap, Robert ; Holland, David ; Feng, Pei-Jean ; Millet, Joan-Pau ; Caylà, Joan A. ; Martinson, Neil A. ; Wright, Alicia ; Chen, Michael P. ; Moro, Ruth N. ; Scott, Nigel A. ; Arevalo, Bert ; Miró, José M. ; Villarino, Margarita E. ; Weiner, Marc ; Borisov, Andrey S.
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• Description:
  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 direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration 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.
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• Subjects:
  • Article
  • Adult
  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Directly Observed Therapy
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Isoniazid
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• Source:
  Ann Intern Med. 167(10):689-697
• Pubmed ID:
  29114781
• Pubmed Central ID:
  PMC5766341
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  167
• Issue:
  10
• Download URL:
  https://stacks.cdc.gov/view/cdc/50870/cdc_50870_DS1.pdf
• File Type:
  [PDF - 728.03 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:1eaf3d3079d1c6c2a5cf2e5f036c08a2dacf84093d97486506f106471a434d7e