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

Details

• 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.
• 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.
  
  
• Subjects:
  Adult Antibiotics, Antitubercular Antitubercular Agents Article Directly Observed Therapy Drug Administration Schedule Drug Therapy, Combination Female Humans Isoniazid Latent Tuberculosis Male Medication Adherence Middle Aged Reminder Systems Rifampin Self Administration Text Messaging

  More +
• 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
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:1eaf3d3079d1c6c2a5cf2e5f036c08a2dacf84093d97486506f106471a434d7e
• Download URL:
  https://stacks.cdc.gov/view/cdc/50870/cdc_50870_DS1.pdf
• File Type:
  [PDF - 728.03 KB ]