Evaluation of the Pharmacokinetics (PK) and Pharmacodymamics (PD) of Ganciclovir (GCV) in Premature Infants Receiving Treatment for Cytomegalorivus (CMV) Infection

NCT ID: NCT01602614

Last Updated: 2020-06-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 18 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2019-03-31

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.

Conditions

Cytomegalovirus Infections

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1

≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.

No interventions assigned to this group

Group 2

≤ 27 weeks 6 days gestational age at birth and \> 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.

No interventions assigned to this group

Group 3

≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.

No interventions assigned to this group

Group 4

≥ 28 weeks 0 days gestational age at birth and \> 30 days chronologic age at study enrollment. Dose and duration of intravenous ganciclovir therapy is at the discretion of the treating physician and will not be dictated by the research protocol.

No interventions assigned to this group

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 180 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

David Kimberlin, MD

Protocol Principal and Lead Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Kimberlin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Birmingham at Alabama

Richard Whitley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

University of South Florida School of Medicine

St. Petersburg, Florida, United States

Louisiana State University Health Science Center - Shreveport

Shreveport, Louisiana, United States

Johns Hopkins Medical Institutions

Baltimore, Maryland, United States

Washington University in St Louis School of Medicine

St Louis, Missouri, United States

Steven & Alexandra Cohen Children's Medical Center of New York (CCMC)

Manhasset, New York, United States

University of Rochester

Rochester, New York, United States

Carolinas Medical Center - Charlotte

Charlotte, North Carolina, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Nationwide Childrens Hospital

Columbus, Ohio, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

F21116007

Identifier Type: -

Identifier Source: org_study_id