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Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial.
Ann Intern Med. 2017 Nov 21; 167(10):689-697.AIM

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.

Authors+Show Affiliations

From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.From Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, Denver, Colorado; Emory University and Fulton County Department of Health and Wellness, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia; Public Health Agency of Barcelona and CIBER de Epidemiología y Salud Pública, Barcelona, Spain; University of the Witwatersrand, Johannesburg, South Africa; Vanderbilt University, Nashville, Tennessee; Westat, Fort Lauderdale, Florida; University of Barcelona, Barcelona, Spain; and University of Texas Health Science Center and Veterans Administration Medical Center, San Antonio, Texas.No affiliation info available

Pub Type(s)

Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

29114781

Citation

Belknap, Robert, et al. "Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: a Randomized Trial." Annals of Internal Medicine, vol. 167, no. 10, 2017, pp. 689-697.
Belknap R, Holland D, Feng PJ, et al. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. Ann Intern Med. 2017;167(10):689-697.
Belknap, R., Holland, D., Feng, P. J., Millet, J. P., Caylà, J. A., Martinson, N. A., Wright, A., Chen, M. P., Moro, R. N., Scott, N. A., Arevalo, B., Miró, J. M., Villarino, M. E., Weiner, M., & Borisov, A. S. (2017). Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. Annals of Internal Medicine, 167(10), 689-697. https://doi.org/10.7326/M17-1150
Belknap R, et al. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: a Randomized Trial. Ann Intern Med. 2017 Nov 21;167(10):689-697. PubMed PMID: 29114781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection: A Randomized Trial. AU - Belknap,Robert, AU - Holland,David, AU - Feng,Pei-Jean, AU - Millet,Joan-Pau, AU - Caylà,Joan A, AU - Martinson,Neil A, AU - Wright,Alicia, AU - Chen,Michael P, AU - Moro,Ruth N, AU - Scott,Nigel A, AU - Arevalo,Bert, AU - Miró,José M, AU - Villarino,Margarita E, AU - Weiner,Marc, AU - Borisov,Andrey S, AU - ,, Y1 - 2017/11/07/ PY - 2017/11/9/pubmed PY - 2017/12/12/medline PY - 2017/11/9/entrez SP - 689 EP - 697 JF - Annals of internal medicine JO - Ann. Intern. Med. VL - 167 IS - 10 N2 - 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. SN - 1539-3704 UR - https://www.unboundmedicine.com/medline/citation/29114781/full_citation L2 - https://www.annals.org/aim/fullarticle/doi/10.7326/M17-1150 DB - PRIME DP - Unbound Medicine ER -