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 May 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: May 18, 2014
Last verified: May 2014
  Purpose

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.


Condition
Cytomegalovirus Infections

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Evaluation of the Pharmacokinetics and Pharmacodynamics of Ganciclovir in Premature Infants Receiving Treatment for Cytomegalovirus Infection

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples Without DNA

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.


Estimated Enrollment: 32
Study Start Date: April 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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 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.

  Eligibility

Ages Eligible for Study:   up to 180 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Premature infants who receive intravenous ganciclovir as part of clinical care

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01602614

Contacts
Contact: Bari Cotton, RN 205-934-2424 bcotton@peds.uab.edu
Contact: Penelope M Jester, RN, MPH 205-934-2424 pjester@peds.uab.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: David Kimberlin, MD    877-975-7280    dkimberlin@peds.uab.edu   
Contact: Bari Cotton, RN    205-934-2424    bcotton@peds.uab.edu   
United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Jose Romero, MD    501-364-1416    romeroJose@uams.edu   
Principal Investigator: Jose Romero, MD         
United States, Colorado
University of Colorado at Denver Health Sciences Center Not yet recruiting
Denver, Colorado, United States, 80045
Contact: Mark J Abzug, MD    720-777-6389    abzug.mark@tchden.org   
Principal Investigator: Mark J Abzug, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Roberta L Debiasi, MD    202-476-5051    rdebiasi@cnmc.org   
Principal Investigator: Roberta L DeBiasi, MD         
United States, Florida
University of South Florida School of Medicine Recruiting
Tampa, Florida, United States, 33606
Contact: Jorge Lujan-Zilbermann, MD    813-259-8800    jlujanzi@health.usf.edu   
Principal Investigator: Jorge Lujan-Zilbermann, MD         
United States, Louisiana
Louisiana State University Health Science Center - Shreveport Recruiting
Shreveport, Louisiana, United States, 71103
Contact: John Vanchiere, MD, PhD    318-675-7877    jvanch@lshusc.edu   
Principal Investigator: John Vanchiere, MD, PhD         
United States, Maryland
Johns Hopkins Medical Institutions Recruiting
Baltimore, Maryland, United States, 21287
Contact: Ravit Boger, MD    410-614-3917    boger@jhmi.edu   
Principal Investigator: Ravit Boger, MD         
United States, Missouri
Washington University in St Louis School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Gregory Storch, MD    314-454-6079    storch_G@kids.wustl.edu   
Principal Investigator: Gregory Storch, MD         
United States, New York
Steven & Alexandra Cohen Children's Medical Center of New York (CCMC) Recruiting
Manhasset, New York, United States, 11030
Contact: Sunil Sood, MD    516-562-3957    sood@lij.edu   
Principal Investigator: Sunil Sood, MD         
United States, North Carolina
Carolinas Medical Center - Charlotte Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Amina Ahmed, MD, BS    704-381-6870    amina.ahmed@carolinashealthcare.org   
Principal Investigator: Amina Ahmed, MD, BS         
United States, Ohio
MetroHealth Medical Center Recruiting
Cleveland, Ohio, United States, 44109
Contact: Nazha F Abughali, MD    216-778-3402    nabughali@metrohealth.org   
Principal Investigator: Nazha F Abughali, MD         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Marian J Michaels, MD, MPH    412-692-6786    marian.michaels@chp.edu   
Principal Investigator: Marian J Michaels, MD, MPH         
United States, Rhode Island
Rhode Island Hospital Not yet recruiting
Providence, Rhode Island, United States, 02903
Contact: Penelope Dennehy, MD    401-444-8360    pdennehy@lifespan.org   
Principal Investigator: Penelope Dennehy, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Natasha B Halasa, MD, MPH    615-322-3346    natasha.halasa@vanderbilt.edu   
Principal Investigator: Natasha B Halasa, MD, MPH         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: David Kimberlin, MD University of Birmingham at Alabama
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: David Kimberlin, MD, Protocol Principal and Lead Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01602614     History of Changes
Other Study ID Numbers: F21116007
Study First Received: May 17, 2012
Last Updated: May 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Infection
Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Ganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014