Details:

Alternative Title:
Ann Intern Med
Personal Author:
Belknap, Robert ; Holland, David ; Feng, Pei-Jean ; Millet, Joan-Pau ; Caylà, Joan A. ; ... More +
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. Less -
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:
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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
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/
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:

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