1323. Tolerability among children of three months of once-weekly rifapentine + INH (3HP) vs. 9 months of daily INH (9H) for treatment of latent tuberculosis infection: The PREVENT TB Study (TBTC Study 26/ACTG 5259)
Session: Oral Abstract Session: Clinical Management of Infectious Disease
Saturday, October 20, 2012: 11:45 AM
Room: SDCC 26 AB
Background: In the PREVENT TB study, 3 months of once-weekly rifapentine 900 mg + INH 900 mg under direct observation (3HP-DOT) was at least as effective as 9H in a population of mostly HIV-seronegative adults (NEJM 2011).

Methods: Children 2-17 years old who were close contacts of infectious TB were enrolled between June 2001 and December 2010. Enrollment of children <12 years into PREVENT TB was extended 22 months past the last enrollment of HIV negative adults and adolescents to enrich this study population.  Children were treated with protocol-specified, age- and weight-adjusted treatment regimens. We gave a slurry of crushed tablets in food to children unable to swallow whole tablets. We report here on regimen tolerability.  Follow-up continues for the primary endpoint of TB disease.

Results: 1,058 children were enrolled from the US/Canada (884), Brazil (171), Hong Kong (2) and Spain (1). Of these, 1,032 received >1 dose of therapy and are in the tolerability analysis. Median (IQR) age was 11(4-15) years; the population was 51% male, 71% white, 14% black, and of those enrolled at US/Canada sites, 73% Hispanic. Five (0.5%) were HIV-infected. 

Tolerability Outcomes

9H (n=493)

3HP (n=539)

P-value

Completion of study treatment regimen*

350/436 (80.3)

417/473 (88.2)

0.001

Drug d/c due to adverse event (AE)**

4 (0.8)

7 (1.3)

0.55

Grade 3 toxicity AEs

6 (1.2)

6 (1.1)

1.0

Grade 4 toxicity AEs

2 (0.4)

1 (0.2)

0.61

Death (Grade 5 toxicity)*

2/436 (0.5)

0/473

0.23

Possible hypersensitivity (HS)†

0

7 (1.3)

0.02

Hepatotoxicity

0

0

N/A

*Among MITT study population (enrolled and eligible to complete study)

 ** Events: 4 possible HS, 3 pruritic rashes, 2 non-pruritic rashes, 1 GI intolerance and 1 concomitant diagnosis (Kawasaki’s Disease)

1 severe (Grade 3 oral blisters and fever) and 6 mild-moderate

Conclusion: As in adults, 3HP-DOT had higher treatment completion in children, with no difference in grade 3/4/5 toxicity, but more cases of possible drug HS than 9H. Drug d/c due to AEs was similar by treatment arm (not higher in 3HP-DOT as in adults) and there were no cases of hepatotoxicity.  The once-weekly, short duration 3HP-DOT regimen was generally well-tolerated and offers substantial advantages compared to the current standard of 9H for treatment of LTBI in children.

Elsa Villarino, MD, MPH1, Nigel Scott, MS1, Stephen Weis, DO2, Marc Weiner, MD3, Marcus Conde, MD4, Brenda Jones, MD5, Sharon Nachman, MD6, Ricardo Oliveira, MD7, Nong Shang, PhD1, Timothy Sterling, MD8 and IMPAACT and TB Trials Consortium, (1)Centers for Disease Control and Prevention, Atlanta, GA, (2)University of North Texas Health Sciences, Fort Worth, TX, (3)South Texas Veterans Health Care System, San Antonio, TX, (4)TB Trials Consortium, Rio de Janeiro, Brazil, (5)Los Angeles County-University of Southern California Medical Center, Los Angeles, CA, (6)SUNY Stony Brook, Stony Brook, NY, (7)IMPAACT, Rio de Janeiro, Brazil, (8)Division of Infectious Diseases, Vanderbilt University, Nashville, TN

Disclosures:

E. Villarino, None

N. Scott, None

S. Weis, None

M. Weiner, None

M. Conde, None

B. Jones, None

S. Nachman, None

R. Oliveira, None

N. Shang, None

T. Sterling, None

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