Source:

Villarino
ME
,
Scott
NA
,
Weis
SE
, et al
.
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
.
JAMA Pediatr
.
2015
;
169
(
3
):
247
255
; doi:
https://doi.org/10.1001/jamapediatrics.2014.3158

Investigators at 29 international sites conducted a randomized clinical trial to evaluate the safety and effectiveness of a short course of combination therapy in treating latent tuberculosis (TB) infection in children and adolescents. Children were eligible to participate if they were 2–17 years old and met high risk criteria for TB, according to age, TB skin test results, and TB exposure history. Enrolled participants were randomized to receive either a 3-month course of combined rifapentine plus isoniazid (given on a once-weekly basis) or daily isoniazid-only for 9 months. Weekly rifapentine-isoniazid doses were given under direct supervision by a health care professional, while isoniazid doses were supplied monthly for daily self-administration.

Primary outcomes were adverse events (AEs) and TB diagnosis within 33 months of enrollment. Study clinicians followed the children for clinical status and AEs at regular intervals during the study through a 33-month follow-up period. A TB diagnosis was confirmed by either a positive culture for Mycobacterium tuberculosis in a study participant or a clinical diagnosis meeting diagnostic criteria established by the American Thoracic Society and Centers for Disease Control and Prevention. The goals of the study were to determine equivalency of combination therapy, compared to daily isoniazid, in terms of AEs, defined as <5% difference in rates of discontinuing therapy (because of AEs), and effectiveness in preventing TB.

Of 1,058 children enrolled, including 552 in the combination therapy group and 506 in the isoniazid-only treatment group, 905 were eligible for evaluation for effectiveness and 766 completed treatment. Treatment completion differed between the 2 groups, with 415 of 471 evaluable children (88.1%) completing weekly combination therapy and 351 of 434 evaluable children (80.9%) completing daily monotherapy (P = .003). Loss of contact for ≥3 months significantly contributed to completion failure in the monotherapy group compared to the combination therapy group (P < .001). Among study patients receiving combination therapy, 1.7% discontinued the medications for reasons related to AEs, while 0.5% stopped isoniazid-only for reasons related to AEs (P = .11). There was no hepatotoxicity, serious AE, or death attributed to the study drugs. None of the 471 children with combination prophylaxis developed TB, whereas 3 of the 434 children (0.74%) who received isoniazid-only had progression to TB.

The authors conclude that combining rifapentine and isoniazid as a weekly supervised dose for 3 months is as safe and effective as daily self-administered isoniazid only for 9 months to prevent TB disease in children and adolescents with latent TB infection.

Dr Santisteban-Ponce has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Nearly 1 million children worldwide develop TB each...

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