A Randomized, Double-Blind, Placebo-Controlled Trial of Pleconaril for the Treatment of Neonates With Enterovirus Sepsis.
J Pediatric Infect Dis Soc
; 5(1): 53-62, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26407253
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 21 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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Oxidiazóis
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Enterovirus
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Infecções por Enterovirus
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Sepse Neonatal
Tipo de estudo:
Clinical_trials
Limite:
Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
J Pediatric Infect Dis Soc
Ano de publicação:
2016
Tipo de documento:
Article