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

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 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.

Adherence to treatment in allergic rhinitis using mobile technology. The MASK Study

“…Adherence in randomized control trials is high but does not reflect the real‐life situation, and alternative measurement of adherence in a real‐life setting is needed. The best studies would be using electronic devices that count and record the drugs taken.…”

Latent tuberculosis infection: Opportunities and challenges

“…Treatment completion with self‐administered 3HP in Hong Kong, Spain and the US was lower than DOT but comparable to prior reports of self‐administered rifampin . Completion with self‐administered therapy in South Africa was much lower than DOT and may have reflected the population enrolled which is not routinely offered LTBI treatment by local programmatic guidelines …”

“…61 Treatment completion with self-administered 3HP in Hong Kong, Spain and the US was lower than DOT but comparable to prior reports of self-administered rifampin. 62 Completion with self-administered therapy in South Africa was much lower than DOT and may have reflected the population enrolled which is not routinely offered LTBI treatment by local programmatic guidelines. 62 A recent updated network meta-analysis of 61 studies reaffirmed the evidence for the efficacy and safety of 6-month INH monotherapy, rifampicin monotherapy and combination therapies with 3-4 months of INH and rifampicin.…”

“…62 Completion with self-administered therapy in South Africa was much lower than DOT and may have reflected the population enrolled which is not routinely offered LTBI treatment by local programmatic guidelines. 62 A recent updated network meta-analysis of 61 studies reaffirmed the evidence for the efficacy and safety of 6-month INH monotherapy, rifampicin monotherapy and combination therapies with 3-4 months of INH and rifampicin. 63 A large clinical trial of daily rifampin for 4 months has been completed and the results of that trial are expected soon.…”

Tuberculosis Screening and Treatment in Solid Organ Transplantation

“…A combination of weekly rifapentine and isoniazid for 12 weeks (3HP) is also as effective as 9H and, like 4R, and is associated with higher rates of treatment completion [34]. While initially recommended only in the context of directly observed therapy, 3HP has subsequently been found to be efficacious as self-administered therapy and recommendations now permit both treatment administration options [35,36]. While hepatotoxicity is less common with 3HP compared to 9H, more patients on 3HP had to permanently discontinue the regimen due to ADRs [34].…”