Randomized trial suggests that self-administered latent tuberculosis treatment is noninferior to direct observation

1. Once-weekly isoniazid (INH) and rifapentine treatment for latent tuberculosis infection (LTBI) via self-administered therapy (SAT) had high completion rates in the United States (U.S.), Spain, and Hong Kong, and SAT was found to be noninferior to directly observed therapy (DOT) in the U.S.

2. Adverse events were similar in all groups and similar to previous reports.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: LTBI transitioning to active infection constitutes approximately 86% of active TB cases in the U.S., which makes LTBI diagnosis and treatment important for preventing active cases.  Although once-weekly INH and rifapentine under DOT for 3 months is as effective as daily INH SAT for 9 months, DOT is often too costly for TB programs, not offered by primary care providers, and not accepted by patients.  This randomized clinical trial compared completion of treatment and safety of once-weekly INH and rifapentine via DOT to that via SAT.  Of treatment sites in four countries studied, researchers found that rates of SAT treatment completion were high in the U.S., Spain, and Hong Kong.  The study design did not allow the cause of low completion rates in South Africa to be determined.  In the U.S., SAT without reminders was noninferior to DOT.  Noninferiority criteria were not met by SAT-with-reminders groups in the U.S. or SAT groups with or without reminders in the other countries.  Adverse events were few and similar for all groups.  Study results suggest that once-weekly INH and rifapentine SAT could be a suitable treatment option for LTBI in the U.S. and in areas where DOT is unfeasible.

Strengths of the study include participants representative of LTBI patients receiving treatment at public health clinics and use of multiple U.S. treatment sites, which may assist in generalizability in the U.S.  A limitation is that more complicated packaging (compared to clinical use) used to organize medication doses and to track pill bottle openings may have been a factor in reduced treatment completion for the SAT groups.  Also, receipt of reminders was not confirmed for patients in the SAT-with-reminders group.

Click to read the study in Annals of Internal Medicine

Click to read an accompanying editorial in Annals of Internal Medicine 

Relevant Reading: Tuberculosis treatment outcomes: directly observed therapy compared with self-administered therapy

In-Depth [randomized controlled trial]: This phase 4 randomized clinical trial included 1002 participants ≥18 years of age who were recommended for LTBI treatment.  Participants were a median age of 36 years, 48% women, and 77% enrolled at sites in the U.S.  The study was conducted at 9 U.S. sites and 1 site each in Spain, Hong Kong, and South Africa.  Participants received once-weekly INH and rifapentine via DOT, SAT with monitoring each month, or SAT with both monthly monitoring and weekly text message reminders.  The primary and secondary outcomes were completion of treatment (≥11 doses within 16 weeks) and adverse events, respectively.  The study design was a noninferiority trial with a maximum treatment completion decrease of 15%.  Overall, treatment completion for the DOT, SAT, and SAT-with-reminders groups were 87.2%, 74.0%, and 76.4%, respectively.  In the U.S., treatment completion for the DOT, SAT, and SAT-with-reminders groups were 85.4%, 77.9%, and 76.7%, respectively.  Adverse events (total, drug-related, and severe) were similar in all groups and similar to previous reports.

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