Evaluation of the Pharmacokinetics (PK) and Pharmacodymamics (PD) of Ganciclovir (GCV) in Premature Infants Receiving Treatment for Cytomegalorivus (CMV) Infection
Condition: Cytomegalovirus Infections
MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections
Study type: Observational

Summary: 
      This is a clinical sampling study, and no study drugs will be administered under this
      protocol. Premature infants who receive intravenous ganciclovir as part of clinical care will
      be eligible for participation in this study. Intravenous ganciclovir will not be provided
      under this protocol.
    

Detailed description: 
      This is an open-label, multi-center, clinical sampling study to assess ganciclovir
      pharmacokinetics and pharmacodynamics in premature infants. Only those subjects who receive
      ganciclovir for clinical reasons will be enrolled. The decision to initiate ganciclovir
      therapy will be made by the attending physician based upon his/her clinical decision to treat
      virologically-confirmed CMV infection; infants receiving such therapy and meeting entry
      criteria will then be eligible for this study. Therefore, ganciclovir will not provided under
      this protocol.

      Subjects meeting enrollment criteria will be entered into this clinical trial. Subjects will
      be stratified by gestational age and by chronologic age as follows: 1) ≤ 27 weeks 6 days
      gestational age at birth and ≤ 30 days chronologic age at study enrollment; 2) ≤ 27 weeks 6
      days gestational age at birth and > 30 days chronologic age at study enrollment; 3) ≥ 28
      weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment; 4) ≥
      28 weeks 0 days gestational age at birth and > 30 days chronologic age at study enrollment.
      Eight subjects will enroll in each of the four groups, for a total sample size of 32
      subjects. Subjects in each cohort with inadequate pharmacokinetic data for analysis (e.g.,
      due to dropping out of the study before PK assessments are performed, or blood sampling
      obtained but is inadequate for analysis) will be replaced and will not count toward the total
      of eight subjects in each of the four groups. Additionally, enrollment of an additional 2-3
      subjects may be allowed for operational reasons.

      A full pharmacokinetic profile will be obtained with one of the ganciclovir doses received
      after enrollment. PK assessments will be obtained after the subject has received study
      assessment dose 3, 4, 5, 6, 7, or 8 of intravenous ganciclovir. Specimens will be shipped for
      processing at that time. The pharmacokinetic data will then be provided to the study site,
      including the area under curve (AUC) and clearance (CL) values for information purposes.

      Duration of intravenous ganciclovir therapy is at the discretion of the treating physician
      and will not be dictated by the research protocol. Both whole blood for CMV polymerase chain
      reaction (PCR) and urine for CMV detection will be obtained once in each study period as long
      as the subject is receiving intravenous ganciclovir therapy. These specimens will be used to
      determine blood viral load and ganciclovir resistance. Since ganciclovir is a renally
      excreted drug, serum creatinine will be drawn for the research protocol on the day that the
      ganciclovir pharmacokinetic specimens are obtained in order to calculate creatinine clearance
      using a method such as the modified Schwartz formula, and thus correlate ganciclovir
      clearance with renal function. Otherwise, data from hematology assessments (WBC count and
      differential, hemoglobin, platelet count) and from chemistry labs (serum creatinine,
      aspartate aminotransferase (AST) , and alanine aminotransferase (ALT) will be recorded on the
      study case report forms during each study period if they are being obtained for clinical
      reasons, but will not be drawn only for the purposes of the study. Ganciclovir dosing
      information (mg/dose, dosing interval, and patient weight) will be recorded on the day of the
      pharmacokinetic blood draws, and weekly from Period 1 through Period 7 as long as the subject
      is receiving intravenous ganciclovir therapy.

      If the patient continues to receive intravenous ganciclovir from Study Assessment Day 18
      through Study Assessment Day 24 (Period 4), a second PK assessment may be performed at the
      request of the treating physician if the subject weighs 575 grams or more at the time of
      specimen collection.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Premature infants who receive intravenous ganciclovir as part of clinical care
      
Biospecimen description: 
      Remnant blood will be retained for future cytomegalovirus (CMV) studies if subjects/subject
      families consent to future use. Institutional Review Board (IRB) approval for any future
      studies of remnant specimens will be required.