Clinical trial NCT01602614: Evaluation of the Pharmacokinetics (PK) and Pharmacodymamics (PD) of Ganciclovir (GCV) in Premature Infants Receiving Treatment for Cytomegalorivus (CMV) Infection
Official title: Evaluation of the Pharmacokinetics and Pharmacodynamics of Ganciclovir in Premature Infants Receiving Treatment for Cytomegalovirus Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cytomegalovirus Infections
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2012-05-21
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 180
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Premature infants who receive intravenous ganciclovir as part of clinical care

Brief 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.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent from parent(s) or legal guardian(s)
2. Confirmation of CMV infection from urine, blood, or saliva by culture, shell vial, or PCR tests (local lab)
3. Receiving intravenous ganciclovir, prescribed by the patient's physician
4. \< 32 weeks gestational age at birth
5. ≥ 500 grams at study enrollment

Exclusion Criteria:

1. Imminent demise
2. Current receipt of valganciclovir or foscarnet
3. Receiving breast milk from a mother who is being treated with ganciclovir or valganciclovir
4. Current receipt of other investigational drugs
5. Major congenital anomaly that in the site investigator's opinion may impact drug metabolism or the patient's volume of distribution

Primary outcomes:
measure: Plasma Pharmacokinetics Parameters for Ganciclovir Area Under the Curve at 12 Hours (AUC12mgxh/L)
timeFrame: within 12 hours after dose administration
Secondary outcomes:
measure: Plasma Pharmacokinetics Parameters for Ganciclovir, Including Maximum Serum Concentration (Cmax mg/L).
timeFrame: within 12 hours after dose administration
measure: Plasma Pharmacokinetics Parameters for Ganciclovir for Half-life (T1/2 hr).
timeFrame: within 12 hours after dose administration
measure: Plasma Pharmacokinetics Parameters for Ganciclovir for Clearance (Cl L/hr/kg).
timeFrame: within 12 hours after dose administration
measure: Plasma Pharmacokinetics Parameters for Ganciclovir for Volume of Distribution (Vd L).
timeFrame: within 12 hours after dose administration
measure: Correlation of Ganciclovir Plasma Pharmacokinetics (Clearance (CL) With Whole Blood Cytomegalovirus (CMV) Viral Load.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Maximum Serum Concentration (Cmax) With Whole Blood Cytomegalovirus (CMV) Viral Load.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Area Under the Curve (AUC12) With Whole Blood Cytomegalovirus (CMV) Viral Load.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Half-life (T1/2) With Whole Blood Cytomegalovirus (CMV) Viral Load.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Volume of Distribution (Vd) With Whole Blood Cytomegalovirus (CMV) Viral Load.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Clearance (Cl) With Clearance of CMV in Urine
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Maximum Serum Concentration (Cmax) With Clearance of CMV in Urine.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Area Under the Curve (AUC) With Clearance of CMV in Urine.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Maximum Serum Half Life (T1/2) With Clearance of CMV in Urine.
timeFrame: 6 weeks
measure: Correlation of Ganciclovir Plasma Pharmacokinetics Volume of Distribution (Vd) With Clearance of CMV in Urine.
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: University of South Florida School of Medicine
state: Florida
city: Shreveport
country: United States
facility: Louisiana State University Health Science Center - Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Medical Institutions
state: Maryland
city: Saint Louis
country: United States
facility: Washington University in St Louis School of Medicine
state: Missouri
city: Manhasset
country: United States
facility: Steven & Alexandra Cohen Children's Medical Center of New York (CCMC)
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center - Charlotte
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: University of Birmingham at Alabama
name: David Kimberlin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Richard Whitley, MD
role: PRINCIPAL_INVESTIGATOR
References: