PMID- 25580725 OWN - NLM STAT- MEDLINE DCOM- 20150430 LR - 20210717 IS - 2168-6211 (Electronic) IS - 2168-6203 (Print) IS - 2168-6203 (Linking) VI - 169 IP - 3 DP - 2015 Mar TI - Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid. PG - 247-55 LID - 10.1001/jamapediatrics.2014.3158 [doi] AB - IMPORTANCE: Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data for children are limited. OBJECTIVES: To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children. DESIGN, SETTING, AND PARTICIPANTS: A pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2-17 years) who were eligible for treatment of latent tuberculosis infection. INTERVENTIONS: Twelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months. MAIN OUTCOMES AND MEASURES: We compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%. RESULTS: Of 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was -2.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of -0.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion. CONCLUSIONS AND RELEVANCE: Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00023452. FAU - Villarino, M Elsa AU - Villarino ME AD - Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. FAU - Scott, Nigel A AU - Scott NA AD - Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia2CDC Foundation, Atlanta, Georgia. FAU - Weis, Stephen E AU - Weis SE AD - Department of Medicine, University of North Texas Health Science Center at Ft Worth. FAU - Weiner, Marc AU - Weiner M AD - Department of Medicine, Audie L. Murphy San Antonio Veterans Administration Medical Center, San Antonio, Texas. FAU - Conde, Marcus B AU - Conde MB AD - Department of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Jones, Brenda AU - Jones B AD - Department of Medicine, University of Southern California, Los Angeles. FAU - Nachman, Sharon AU - Nachman S AD - Department of Pediatrics, State University of New York at Stony Brook. FAU - Oliveira, Ricardo AU - Oliveira R AD - Department of Pediatrics, Pediatric Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Moro, Ruth N AU - Moro RN AD - Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia2CDC Foundation, Atlanta, Georgia. FAU - Shang, Nong AU - Shang N AD - Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. FAU - Goldberg, Stefan V AU - Goldberg SV AD - Division of Tuberculosis Elimination, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia. FAU - Sterling, Timothy R AU - Sterling TR AD - Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. CN - International Maternal Pediatric and Adolescents AIDS Clinical Trials Group CN - Tuberculosis Trials Consortium LA - eng SI - ClinicalTrials.gov/NCT00023452 GR - CC999999/Intramural CDC HHS/United States GR - P30 AI050409/AI/NIAID NIH HHS/United States GR - P30 AI094189/AI/NIAID NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Pediatr JT - JAMA pediatrics JID - 101589544 RN - 0 (Antitubercular Agents) RN - V83O1VOZ8L (Isoniazid) RN - VJT6J7R4TR (Rifampin) RN - XJM390A33U (rifapentine) SB - IM CIN - JAMA Pediatr. 2015 Mar;169(3):208-10. PMID: 25581905 CIN - Indian Pediatr. 2015 May;52(5):421-5. PMID: 26061929 EIN - JAMA Pediatr. 2015 Sep;169(9):878. PMID: 26348861 MH - Adolescent MH - Antitubercular Agents/administration & dosage/adverse effects/*therapeutic use MH - Child MH - Child, Preschool MH - Drug Therapy, Combination MH - Female MH - Humans MH - Isoniazid/administration & dosage/adverse effects/*therapeutic use MH - Latent Tuberculosis/*prevention & control MH - Male MH - Rifampin/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use MH - Treatment Outcome PMC - PMC6624831 MID - NIHMS926789 COIS- Conflict of Interest Disclosures: Mr Scott and Dr Moro report being employed by the CDC Foundation, which receives funds for rifapentine research from Sanofi. Dr Weiner reports receiving a grant to perform rifapentine pharmacokinetics studies in children and adults for the University of Texas Health Science Center at San Antonio from Sanofi. Dr Sterling reports giving a 1-day consultation for Sanofi for presentation of PREVENT TB study data to the US Food and Drug Administration and being on the data safety monitoring board for a clinical trial sponsored by Otsuka Pharmaceutical. No other disclosures were reported. 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Starke, Jeffrey IR - Starke J EDAT- 2015/01/13 06:00 MHDA- 2015/05/01 06:00 PMCR- 2019/07/12 CRDT- 2015/01/13 06:00 PHST- 2015/01/13 06:00 [entrez] PHST- 2015/01/13 06:00 [pubmed] PHST- 2015/05/01 06:00 [medline] PHST- 2019/07/12 00:00 [pmc-release] AID - 2089639 [pii] AID - 10.1001/jamapediatrics.2014.3158 [doi] PST - ppublish SO - JAMA Pediatr. 2015 Mar;169(3):247-55. doi: 10.1001/jamapediatrics.2014.3158.