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.
This study is closed to enrollment. The final enrolled number was 88.
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.