Pleconaril Enteroviral Sepsis Syndrome
Condition: Enterovirus Infection
MeSH terms: Sepsis; Enterovirus Infections; Toxemia; Systemic Inflammatory Response Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      A common group of viruses that infect humans are enteroviruses. Enteroviruses produce
      illnesses in children which may range from very mild (summer colds) to severe (infections of
      the brain, liver, and heart). The purpose of this study is to determine if a new drug called
      pleconaril helps treat babies with enteroviral sepsis. In addition, researchers are
      attempting to determine a safe and effective dose of pleconaril to help babies with this
      disease. Infants who are 15 days or younger when diagnosed with enteroviral disease are
      eligible for this study. Two out of 3 babies will be randomly assigned to receive Pleconaril
      and the other one out of three will receive a placebo (inactive substitute). Participants
      will be hospitalized while receiving study medication. Babies will receive standard treatment
      care for their symptoms and will be observed for their medical progress. Participants may be
      in the study for up to 2 years.
    

Detailed description: 
      Enteroviral infection is a serious health problem in the newborn infant. Approximately 60-70%
      of infants diagnosed with enteroviral disease within the first 10 days of life acquire their
      infection by transmission from the mother at the time of delivery. Congenital infection is
      rare but often fatal. Perinatal transmission of enteroviral infections in newborn nurseries
      has also been implicated as an important route of spread of the disease in newborn infants
      and postnatal transmission of enteroviral infections during seasonal peaks of enterovirus
      activity occurs commonly. Thus, during periods of high prevalence of enterovirus infection in
      the community, there are many potential sources of infection both during and after discharge
      from the nursery, including the mother, other family members, and hospital staff.
      Approximately 75% of cases of neonatal enteroviral disease carry a benign outcome, with
      diagnosis and symptomatic treatment in non-intensive care unit settings. For the remainder of
      patients, more serious consequences can result from systemic enteroviral infection, including
      meningoencephalitis, cardiovascular collapse, myocarditis, or hepatitis. These last two
      organ-specific complications carry high mortality rates. Historically, symptom management and
      supportive care have been the rule in the management of these patients. No specific
      therapeutic intervention is currently available for the management of these gravely ill
      neonates. The current study will evaluate the antiviral drug pleconaril as a treatment for
      enterovial sepsis syndrome. This trial is a multi-center, randomized, placebo-controlled
      study to evaluate the virologic efficacy, safety, and pharmacokinetics of pleconaril in the
      treatment of severe enteroviral sepsis syndrome. Patients will be randomized 2:1 to drug or
      placebo. For enrollment into this trial, infants must have evidence of severe hepatic
      involvement, myocardial involvement, and/or consumptive coagulopathy. Their age must be 15
      days or less at the time of the onset of disease symptoms. Enrollment will continue until 45
      subjects with confirmed enteroviral disease have been enrolled. The primary objective of this
      investigation is to determine if administration of pleconaril to critically ill neonates with
      enteroviral sepsis syndrome results in more rapid clearance of virus from various body sites.
      Other objectives of this study are to assess the safety and pharmacokinetics of this drug in
      this patient population. The effects of pleconaril on measures of clinical outcome also will
      be evaluated. These include the degree of inotropic and blood product support required during
      the acute illness; duration of hospitalization; the time to resolution of residual organ
      injury; and short-term (at 2 months of age) and long-term (at 1 year of age) survival. The
      primary endpoint will be the percentage of patients shedding virus (as detected by viral
      culture) from the oropharynx (i.e. throat) 5 days after beginning study drug. The secondary
      endpoints will include: duration (in days) of shedding of virus (as detected by viral
      culture) from the oropharynx, rectum, urine, and serum; change in baseline laboratory
      abnormalities [aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin,
      platelets, creatinine), reflecting either resolution or progression of enteroviral disease;
      pleconaril pharmacokinetics; safety; duration (in days) of total hospitalization; survival at
      2 months of age; time (in days) to resolution of residual organ-related abnormalities
      following acute disease; and survival at 1 year of age.
    

Intervention name(s): Placebo; Pleconaril
Intervention type(s): Other; Drug
Intervention description(s): Placebo.; 5 mg/kg /dose oral every 8 hours for 7 days (21 doses) of a 40 mg/mL oral liquid formulation and 8.5 mg/kg/dose oral every 8 hours for 7 days (21 doses) of a 40 mg/mL oral suspension formulation.
Intervention MeSH terms: Pleconaril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: enteroviral sepsis; enterovirus; infants; Pleconaril