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Mark J. Abzug, Marian G. Michaels, Ellen Wald, Richard F. Jacobs, José R. Romero, Pablo J. Sánchez, Gregory Wilson, Paul Krogstad, Gregory A. Storch, Robert Lawrence, Mark Shelton, April Palmer, Joan Robinson, Penelope Dennehy, Sunil K. Sood, Gretchen Cloud, Penelope Jester, Edward P. Acosta, Richard Whitley, David Kimberlin, the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, Harley Rotbart, John Modlin, Janet Kinney, John Bradley, Leonard Weiner, Mark McKinlay, Charles Grose, Jeffrey Cohen, Mark Van Raden, Gerald Fisher, Shirley Jankelevich, Sharon Blount, Linda Austin, Dunia Ritchey, Kathryn Edwards, Natasha Halasa, Elizabeth Esterl, Sharolene Goodman, Leslie Smitely, Anna Winborn, Dewan Perry, Fiker Zeray, Shanda Johnson, the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group, A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis, Journal of the Pediatric Infectious Diseases Society, Volume 5, Issue 1, March 2016, Pages 53–62, https://doi.org/10.1093/jpids/piv015
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Abstract
Neonatal enterovirus sepsis has high mortality. Antiviral therapy is not available.
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.
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 IC 90 after the first study day, but 38% were less than the IC 90 during the first day of treatment. One subject in the treatment group and three in the placebo group had treatment-related adverse events.
Shorter times to culture and PCR negativity and greater survival among pleconaril recipients support potential efficacy and warrant further evaluation.
