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Evaluation of the PK and PD of Ganciclovir in Premature Infants Receiving Treatment for CMV Infection (Gan Premie)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
David Kimberlin, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01602614
First received: May 17, 2012
Last updated: November 18, 2014
Last verified: November 2014

May 17, 2012
November 18, 2014
April 2013
July 2016   (final data collection date for primary outcome measure)
Plasma pharmacokinetics parameters for ganciclovir Area Under the Curve at 12 hours (AUC12) [ Time Frame: within 12 hours after dose administration ] [ Designated as safety issue: No ]
A series of blood samples will be collected to assess the ganciclovir levels in the blood at the following time points: 0 hour (immediately prior to intravenous (IV) ganciclovir dose; within 15 min prior to dose), 1 hour (immediately after the end of the IV ganciclovir dose; within 15 min after dose), 2-3 hour, 5-7 hour, and 10-12 hour; required amount of whole blood for plasma ganciclovir determination at each time point is at least 0.2 mL
Same as current
Complete list of historical versions of study NCT01602614 on ClinicalTrials.gov Archive Site
  • Plasma pharmacokinetics parameters for ganciclovir, including maximum serum concentration (Cmax), half-life (T1/2), CL, and Vd [ Time Frame: within 12 hours after dose administration ] [ Designated as safety issue: No ]
  • Correlation of ganciclovir plasma concentrations with CMV whole blood viral load [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Correlation of ganciclovir plasma concentrations with clearance of CMV in urine [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Correlation of ganciclovir plasma concentrations with neutropenia [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Detection of resistance to ganciclovir [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Evaluation of the PK and PD of Ganciclovir in Premature Infants Receiving Treatment for CMV Infection
Evaluation of the Pharmacokinetics and Pharmacodynamics of Ganciclovir in Premature Infants Receiving Treatment for Cytomegalovirus Infection

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.

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 AUC and 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 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, AST, and 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
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:

Remnant blood will be retained for future CMV studies if subjects/subject families consent to future use. IRB approval for any future studies of remnant specimens will be required.

Non-Probability Sample

Premature infants who receive intravenous ganciclovir as part of clinical care

Cytomegalovirus Infections
Not Provided
  • Group 1
    ≤ 27 weeks 6 days gestational age at birth and ≤ 30 days chronologic age at study enrollment
  • Group 2
    ≤ 27 weeks 6 days gestational age at birth and > 30 days chronologic age at study enrollment
  • Group 3
    ≥ 28 weeks 0 days gestational age at birth and ≤ 30 days chronologic age at study enrollment
  • Group 4
    ≥ 28 weeks 0 days gestational age at birth and > 30 days chronologic age at study enrollment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
32
July 2016
July 2016   (final data collection date for primary outcome measure)

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
Both
up to 180 Days
No
Contact: Bari Cotton, RN 205-934-2424 bcotton@peds.uab.edu
Contact: Penelope M Jester, RN, MPH 205-934-2424 pjester@peds.uab.edu
United States
 
NCT01602614
F21116007
Yes
David Kimberlin, MD, University of Alabama at Birmingham
University of Alabama at Birmingham
Not Provided
Principal Investigator: David Kimberlin, MD University of Birmingham at Alabama
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham
University of Alabama at Birmingham
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP