Self-administered treatment with once-weekly isoniazid and rifapentine could be an effective strategy for U.S. patients with latent tuberculosis, a new study indicates.
Researchers at 12 outpatient tuberculosis clinics performed an open-label, phase 4 randomized clinical trial to compare rates of treatment completion and safety with once-weekly isoniazid and rifapentine administered by patients themselves with and without reminders versus direct observation. The trial, which was funded by the CDC and conducted by its Tuberculosis Trials Consortium, was designed as a noninferiority study with a 15% margin (a predetermined maximum difference between treatment approaches acceptable in considering them to be noninferior). The study drugs were provided by Sanofi. Nine of the study sites were in the U.S. and one each were in Spain, Hong Kong, and South Africa.
Patients 18 years of age and older in whom latent tuberculosis treatment had been recommended were randomly assigned to receive once-weekly isoniazid and rifapentine by direct observation, through self-administration with monthly monitoring, or through self-administration with weekly reminders via text message plus monthly monitoring. Treatment completion, defined as at least 11 doses within 16 weeks, was the primary outcome. Clinical documentation and pill counts were used to measure those in the direct observation group, while self-reports, pill counts, and medication event-monitoring systems (MEMS) were used to measure those in the self-administration groups. Adverse event rate was the main secondary outcome. The study results were published online Nov. 7 by Annals of Internal Medicine.
Overall, 1,002 patients screened between September 2012 and April 2014 were enrolled in the study, and 964 were randomly assigned to treatment. Three hundred twenty-eight patients were randomly assigned to directly observed therapy, 321 were assigned to self-administered therapy, and 315 were assigned to self-administered therapy plus reminders. Median age was 36 years. Slightly fewer than half of the patients (48.1%) were women, and 77.2% were enrolled in the U.S. Overall rates of treatment completion were as follows: 87.2% in the direct-observation group, 74.0% in the self-administration group, and 76.4% in the self-administration plus reminders group. Among U.S. patients, treatment completion rates were 85.4%, 77.9%, and 76.7%, respectively, and self-administered therapy with no reminders was noninferior to direct observation. Completion rates with self-administered treatment were high in the U.S., Spain, and Hong Kong but low in South Africa. Rates of drug-related adverse events were similar across study groups: 7.1% in the directly observed group, 8.3% in the self-administered group, and 7.9% in the self-administered plus reminders group.
The authors noted that weekly text messages could not be sent to all patients assigned to the self-monitoring plus reminders group due to access issues and that only one of the study sites was located in a country with a high burden of tuberculosis, among other limitations. However, they concluded that completion rates for once-weekly treatment with isoniazid and rifapentine were high in three of the four study sites and that self-administered therapy with monthly monitoring could be an acceptable strategy for treating latent tuberculosis in the U.S., as well as in other countries and settings when directly observed therapy is not feasible.
In an accompanying editorial, a representative from the World Health Organization's Global TB Programme said the study indicates that self-administered treatment of latent tuberculosis should be promoted in some settings and that shared decision making between patients and clinicians will be needed to determine settings in which self-administration is likely to be successful. “Evidence-based incentives and approaches tailored to the specific needs of patients and their families need to be promoted as part of programmatic management of [latent tuberculosis infection],” the editorialist wrote.