A Study to Describe the Pharmacokinetics of Acyclovir in Premature Infants (PTN_Acyclo)
Condition: Herpes Simplex Virus; Neonatal Sepsis
MeSH terms: Herpes Simplex; Neonatal Sepsis; Premature Birth
Intervention: Acyclovir
Intervention description: Protocol V2 & up: Acyclovir 7mg/ml to be administered IV at 10 mg/kg IV q12 or 20 mg/kg IV q12 or 20 mg/kg IV q8 for a total of 6-9 doses(3 days).
Protocol V1: Acyclovir 5 mg/mL to be administered IV at 500 mg/m2 IV q8h for a total of approximately 15 doses (10 days).
Intervention MeSH terms: Acyclovir
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Maximum age: 45 Days
Healthy volunteers: No
Keywords: HSV; Acyclovir; Pharmacokinetics; Neonate; Premature; Sepsis

Summary:

      Acyclovir is a drug used to treat herpes simplex virus (HSV) infections in babies.
      Appropriate dosing of acyclovir is known for adults and children but acyclovir has not been
      adequately studied in full-term or premature neonates. HSV is a very serious infection in
      babies <6 months of age and often results in death or profound mental retardation. HSV leads
      to profound mental retardation in young infants because the virus attacks the central nervous
      system.

      The investigators hypothesize that the currently recommended dose of acyclovir is inadequate
      to produce adequate blood levels to combat herpes simplex infection. The investigators
      propose to study acyclovir levels in the blood of babies who are placed on acyclovir to treat
      a suspected HSV infection. This will allow them to determine the appropriate dose in
      premature infants. This is an unmet public health need because it is likely that the drug
      behaves differently in premature infants than it does in term infants and older children.
      Premature babies have more body water and less body tissue. Their kidneys are more immature
      and do not function as well as full term infants. Premature neonates are also at the greatest
      risk from herpes infection because they have poorly functioning immature immune systems.
      Early and appropriate treatment with acyclovir has resulted in improved outcome in term
      infants.
    

Eligibility criteria:

        The investigator or other study site personnel will document in the source documents (e.g.,
        the hospital chart) that informed consent was obtained. Laboratory tests or
        non-pharmacologic treatment procedures that were performed as standard of care within 72
        hours prior to first dose of study drug may be used for screening procedures and recorded
        in the CRF.

        Inclusion Criteria

          1. < 45 days of age at the time of initial study drug administration.

          2. Sufficient venous access to permit administration of study medication.

          3. Availability and willingness of the parent/legal guardian to provide written informed
             consent.

          4. Suspected HSV sepsis OR At least two (2) of the following

               -  Signs of sepsis AND negative blood cultures for >24 hours7

               -  Respiratory distress8

               -  Lethargy8

               -  Fever ≥ 38.0°C7

               -  Skin lesions7,8

               -  Seizures (clinical OR EEG confirmed)7

               -  Irritability7

               -  AST OR ALT >2 X upper limit of normal7,8

               -  >20 WBCs/µL or >500 RBCs/µL7

        Exclusion Criteria

          1. History of anaphylaxis attributed to acyclovir.

          2. Serum creatinine >1.7 mg/dL.

          3. Urine output <0.5 mL/kg/hour over the previous 12 hours

          4. Previous participation in the study.

          5. Concomitant condition, which in the opinion of the investigator would preclude a
             participant's participation in the study