학술논문
A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis
Document Type
Academic Journal
Author
Abzug, Mark J.; Michaels, Marian G.; Wald, Ellen; Jacobs, Richard F.; Romero, José R.; Sánchez, Pablo J.; Wilson, Gregory; Krogstad, Paul; Storch, Gregory A.; Lawrence, Robert; Shelton, Mark; Palmer, April; Robinson, Joan; Dennehy, Penelope; Sood, Sunil K.; Cloud, Gretchen; Jester, Penelope; Acosta, Edward P.; Whitley, Richard; Kimberlin, David; Rotbart, Harley; Modlin, John; Kinney, Janet; Bradley, John; Weiner, Leonard; McKinlay, Mark; Grose, Charles; Cohen, Jeffrey; Van Raden, Mark; Fisher, Gerald; Jankelevich, Shirley; Blount, Sharon; Austin, Linda; Ritchey, Dunia; Edwards, Kathryn; Halasa, Natasha; Esterl, Elizabeth; Goodman, Sharolene; Smitely, Leslie; Winborn, Anna; Perry, Dewan; Zeray, Fiker; Johnson, Shanda
Source
Journal of the Pediatric Infectious Diseases Society. Mar 01, 2016 5(1):53-62
Subject
Language
English
ISSN
2048-7193
Abstract
BACKGROUND: Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available. METHODS: Neonates with suspected enterovirus sepsis (hepatitis, coagulopathy, and/or myocarditis) with onset at ≤15 days of life were randomized 2:1 to receive oral pleconaril or placebo for 7 days. Serial virologic (oropharynx, rectum, urine, serum), clinical, pharmacokinetic, and safety evaluations were performed. RESULTS: Sixty-one subjects were enrolled (43 treatment, 18 placebo), of whom 43 were confirmed enterovirus infected (31 treatment, 12 placebo). There was no difference in day 5 oropharyngeal culture positivity (primary endpoint; 0% in both groups). However, enterovirus-infected subjects in the treatment group became culture negative from all anatomic sites combined faster than placebo group subjects (median 4.0 versus 7.0 days, P = .08), and fewer subjects in the treatment group remained polymerase chain reaction (PCR)–positive from the oropharynx when last sampled (23% versus 58%, P = .02; median, 14.0 days). By intent to treat, 10/43 (23%) subjects in the treatment group and 8/18 (44%) in the placebo group died (P = .02 for 2-month survival difference); among enterovirus-confirmed subjects, 7/31 (23%) in the treatment group died versus 5/12 (42%) in the placebo group (P = .26). All pleconaril recipients attained concentrations greater than the IC90 after the first study day, but 38% were less than the IC90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events. CONCLUSIONS: Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.