8604: A Retrospective Follow-up Study of the Durability of Antiviral Therapy on Long-Term Hearing and Neurodevelopmental Outcomes Among Patients Treated for Congenital Cytomegalovirus Infection as Infants or Toddlers (DMID 22-0013)
Background
Overall, congenital cytomegalovirus (CMV) accounts for 21% of hearing loss at birth and 24% of hearing loss by four years of age. The overall cost of treating congenital CMV infection has recently been estimated to be $6.6 billion annually. For these reasons, the National Academy of Medicine (formerly the Institute of Medicine) has prioritized CMV in its top rank of pathogens for which a vaccine is needed.
Because of the low rates of occurrence of congenital CMV infection, meaningful studies must be performed by several research sites. Since the 1980s, the Collaborative Antiviral Study Group (CASG) (now known as the Congenital and Perinatal Infections Consortium, or CPIC) has conducted a series of clinical trials with intravenous (IV) ganciclovir and valganciclovir given by mouth, in the population of babies born with congenital CMV disease with signs and symptoms of the disease at birth, including Phase I/II studies of ganciclovir and valganciclovir and Phase III studies of ganciclovir and valganciclovir. These trials have documented that treating such infants slightly improves hearing and development.
Little is known about the long-term benefits or side effects following ganciclovir/valganciclovir treatment of congenital CMV. Subjects who previously participated in CASG studies will be offered enrollment in this follow-up study. Study activities include a one-time assessment of hearing and development, safety, sexual maturity development, and amount of virus in the body. In addition, patients treated with either ganciclovir by IV or valganciclovir by mouth for congenital CMV infection as part of clinical care at a current or former CASG study site will also be offered participation in the study. It is likely that these patients were managed in a similar manner as those enrolled on a CASG study, including hearing test during and following the completion of the medication, and their inclusion in the current follow-up study will increase understanding of longer-term hearing and safety outcomes.
The discoveries from this follow-up study will impact the next research questions to be posed relating to the treatment of congenital CMV disease. For example, if the study determines that there are no long-term side effects of ganciclovir but the benefits of 6 months of antiviral therapy decreased over time, future studies could then evaluate longer durations of treatment during very early childhood. Such a study could utilize valganciclovir possibly in combination with a new anti-CMV drug such as Letermovir that has a different form of action against CMV. Alternatively, if a large number of children treated in early infancy have delayed initiation of sexual maturity or a large number of cancer events, then the hearing and developmental benefits of therapy would be balanced very differently against such newly learned risks. Such a finding could limit future clinical use of ganciclovir or valganciclovir in neonates and young infants.
This study will enroll about 162 babies at multiple research facilities in the US and UK.
What Happens During This Study?
This study will require one study visit that will take about 4-6 hours. This day can be split over multiple days for convenience of the subjects. During this visit, the following will be done:
- We will look at your medical records to collect some medical history.
- We will collect about 4 teaspoons of blood to look at your hormone levels, the level of the CMV virus in your blood.
- You will have a hearing test done.
- You will have an x-ray done of your wrist.
- You will have a test to see how you are developing compared to other children your age.
- You will have a physical exam to determine if you are maturing like other children your age.
- We will collect some urine.
- We will swab your mouth.
To be eligible to participate, you must:
- Have a signed informed consent from parent(s) or legal guardian(s), with signed assent from subject as appropriate
- Be 2 years or older
- Have one of the following:
- Received ganciclovir or valganciclovir for the treatment of congenital CMV infection at a current or former CASG study site, OR
- Participated in a CASG study of the treatment of congenital CMV
You are not eligible to participate if you have:
- Cannot complete the study related procedures
How to participate?
In order to participate in this study, you must contact the study coordinator or investigator of any of the participating institutions by phone or by email.
Participating Sites
Arkansas Children's Hospital
1 Children's Way
Little Rock, Arkansas, United States, 72202
https://www.archildrens.org/
Baylor College of Medicine - Texas Children's Hospital
6701 Fannin Street
Houston, Texas, United States, 77030
https://www.bcm.edu
Contact:
Principal Investigator:
Gail
Demmler-Harrison
Bristol Royal Hospital for Children
UBHT Education Centre, Level 6, Upper Maudlin Street
Bristol, England, United Kingdom, BS2 8AE
https://www.uhbristol.nhs.uk/patients-and-visitors/your-hospitals/bristol-royal-hospital-for-children/
Contact:
Principal Investigator:
Adam
Finn
Children's Hospital & Medical Center Omaha
8200 Dodge Street
Omaha, Nebraska, United States, 68114
https://www.childrensomaha.org/
Contact:
Principal Investigator:
Kari
Simonsen
+1 402 559 8883
Children's Hospital Colorado
13123 E 16th Avenue
Aurora, Colorado, United States, 80045
https://www.childrenscolorado.org/
Contact:
Principal Investigator:
Mark
Abzug
+1 720 777 6981
Children's Hospital of Orange County
1201 W La Veta Avenue
Orange, California, United States, 92868
https://www.choc.org/
Contact:
Principal Investigator:
Negar
Ashouri
+1 714 532 8403
Children's Hospital of Pittsburgh
4401 Penn Avenue
Pittsburgh, Pennsylvania, United States, 15224
https://www.chp.edu/contact-us
Contact:
Principal Investigator:
Marian
Michaels
+1 412 692 6768
Children's National Medical Center
111 Michigan Avenue NW
Washington, District of Columbia, United States, 20010
https://childrensnational.org/
Contact:
Principal Investigator:
Roberta
DeBiasi
+1 202 476 5052
Cohen Children's Medical Center of New York
269-01 76th Avenue
Queens, New York, United States, 11040
https://childrenshospital.northwell.edu
Contact:
Principal Investigator:
Sunil
Sood
+1 718 470 3415; +1 631 968 3076
Cook Children's Medical Center
801 7th Avenue
Fort Worth, Texas, United States, 76104
https://cookchildrens.org/
Contact:
Principal Investigator:
Mary Suzanne
Whitworth
+1 682 885 1485
Emory University
2015 Uppergate Drive
Atlanta, Georgia, United States, 30322
https://med.emory.edu/departments/pediatrics/
Contact:
Principal Investigator:
Andrea
Shane
+1 404 727 5642
Heartlands Hospital, University Hospitals Birmingham
Bordesley Green
Birmingham, England, United Kingdom, B95SS
https://www.uhb.nhs.uk/
Contact:
Principal Investigator:
Scott
Hackett
Institute of Child Health and Great Ormond Street Hospital for Children
30 Guilford Street
London, England, United Kingdom, WC1N 1EH
https://www.ucl.ac.uk/child-health/
Contact:
Principal Investigator:
Nigel
Klein
John H. Stroger Hospital of Cook County
1901 West Harrsion Street
Chicago, Illinois, United States, 60612
https://cookcountyhealth.org
Contact:
Principal Investigator:
Vish
Agrawal
Johns Hopkins University
3101 Wyman Park Drive
Baltimore, Maryland, United States, 21218
https://www.jhu.edu/
Contact:
Principal Investigator:
Aaron
Milstone
Levine Children's Hospital
1000 Blythe Boulevard
Charlotte, North Carolina, United States, 28203
https://atriumhealth.org/medical-services/childrens-services
Contact:
Principal Investigator:
Amina
Ahmed
Louisiana State University Health Sciences Center at Shreveport
1501 Kings Highway
Shreveport, Louisiana, United States, 71103
https://www.lsuhs.edu/
Contact:
Principal Investigator:
Joseph
Bocchini
Medical University of South Carolina
171 Ashley Avenue
Charleston, South Carolina, United States, 29425
https://research.musc.edu/
Contact:
Principal Investigator:
Sandra
Fowler
Nationwide Children's Hospital - The Ohio State University
700 Children's Drive
Columbus, Ohio, United States, 43205-2664
https://www.nationwidechildrens.org/
Contact:
Principal Investigator:
Pablo
Sanchez
+1 614 355 6638; +1 614 355 5724
North Manchester General Hospital
Limbert House, North Manchester General Hospital
Manchester, England, United Kingdom, M8 5RB
https://mft.nhs.uk/north-manchester-general-hospital/
Contact:
Principal Investigator:
Paddy
McMaster
Rhode Island Hospital
593 Eddy Street
Providence, Rhode Island, United States, 2903
https://www.lifespan.org/locations/rhode-island-hospital
Contact:
Principal Investigator:
Penelope
Dennehy
Royal Victoria Infirmary
Old Children’s Outpatient Building, Queen Victoria Road
Newcastle upon Tyne, England, United Kingdom, NE1 4LP
https://www.newcastle-hospitals.nhs.uk/hospitals/royal-victoria-infirmary/
Contact:
Principal Investigator:
Marieke
Emonts
SUNY Upstate Medical University
750 E Adams Street
Syracuse, New York, United States, 13210
https://www.upstate.edu/
Contact:
Principal Investigator:
Leonard
Weiner
+1 315 464 6331
Seattle Children's Hospital
4800 Sand Point Way NE
Seattle, Washington, United States, 98105
https://www.seattlechildrens.org/
Contact:
Principal Investigator:
Janet
Englund
+1 206 987 2239
Sheffield Children's NHS Foundation Trust
Sheffield Children's NHS Foundation Trust, Western Bank
Sheffield, England, United Kingdom, S10 2TH
https://www.sheffieldchildrens.nhs.uk
Contact:
Principal Investigator:
Fiona
Shackley
Southampton Children's Hospital
University Hospital Southampton NHS Trust, Tremona Road
Southampton, England, United Kingdom, SO16 6YD
https://www.uhs.nhs.uk/
Contact:
Principal Investigator:
Saul
Faust
St. George's Hospital NHS Foundation Trust
Blackshaw Road
London, England, United Kingdom, SW17 0QT
https://www.stgeorges.nhs.uk/
Contact:
Principal Investigator:
Mike
Sharland
St. Peter's University Hospital
254 Easton Avenue
New Brunswick, New Jersey, United States, 8901
http://www.saintpetershcs.com/saintpetersuh/
Contact:
Principal Investigator:
Kristina
Feja
+1 732 339 7605
Stanford University
450 Serra Mall
Stanford, California, United States, 94305
https://www.stanford.edu/
Contact:
Principal Investigator:
Kathleen
Gutierrez
University of Alabama at Birmingham - Administrative Core
1600 7th Avenue S. Children's Harbor, Suite 303
Birmingham, Alabama, United States, 35233
https://www.uab.edu/home/
Contact:
Principal Investigator:
David
Kimberlin,
MD
+1 205 638 2530
University of Louisville
501 East Broadway, Suite 210
Louisville, Kentucky, United States, 40202
https://louisville.edu/
Contact:
Principal Investigator:
Charles
Woods
University of Minnesota
420 Delaware Street
Minneapolis, Minnesota, United States, 55455
https://twin-cities.umn.edu/
Contact:
Principal Investigator:
Jin-Young
Han
University of Mississippi Medical Center
2500 N State Street
Jackson, Mississippi, United States, 39216
https://www.umc.edu/Research/Research_Home.html
Contact:
Principal Investigator:
April
Palmer
+1 601 984 5206
University of Nebraska Medical Center
42nd and Emile Street
Omaha, Nebraska, United States, 68198
https://www.unmc.edu/
University of Rochester
500 Joseph C. Wilson Boulevard
Rochester, New York, United States, 14627
https://www.rochester.edu/
Contact:
Principal Investigator:
Mary
Caserta
+1 585 275 6672
University of South Alabama
1601 Center Street, Suite 1017 C
Mobile, Alabama, United States, 36604
https://www.southalabama.edu/
Contact:
Principal Investigator:
Benjamin
Estrada
+1 251 454 3056
University of South Florida
17 Davis Boulevard
Tampa, Florida, United States, 33606
https://www.usf.edu/
Contact:
Principal Investigator:
Jorge
Lujan-Zilbermann
University of Southern California
1985 Zonal Avenue
Los Angeles, California, United States, 90089-9121
https://www.usc.edu/
Contact:
Principal Investigator:
James
Homans
+1 323 226 2276
University of Texas Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, Texas, United States, 75390
https://www.utsouthwestern.edu/
Contact:
Principal Investigator:
Amanda
Evans
+1 214 648 3720
Vanderbilt University
1211 Medical Center Drive
Nashville, Tennessee, United States, 37232
https://www.vanderbilt.edu
Contact:
Principal Investigator:
Natasha
Halasa
Washington University St. Louis
1 Brookings Drive
St. Louis, Missouri, United States, 63130
https://wustl.edu/
Contact:
Principal Investigator:
Gregory
Storch
+1 314 286 2887