A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

Study ID
HD36801-CMV

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • CTRC Outpatient
  • Children’s Medical Center (Dallas, Plano, Southlake)
  • Parkland Health & Hospital System

Contact


Principal Investigator

Official Title

A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

Brief Overview


Cytomegalovirus (CMV) is a common virus that usually presents with few if any side effects.
When first infected, some people may have symptoms similar to mononucleosis (i.e., fatigue,
weakness, fever, swollen glands). Most people in the United States are infected during
childhood or as adults if they work around children. Pregnant women, who have not been
infected with CMV in the past and become infected during pregnancy (i.e. a primary
infection), may cause their babies to get infected with CMV. Babies that are infected may
develop permanent disabilities including hearing loss and a small portion will die from the
infection.

Currently it is not routine practice to screen pregnant women for CMV infection.
Additionally, there is no agreement about how to evaluate and manage pregnant women infected
with CMV for the first time. There is also no evidence that treatment is beneficial for the
baby.

The purpose of this research study is to determine whether treating pregnant women who have
a primary CMV infection with CMV antibodies will reduce the number of babies infected with
CMV.

Summary


Cytomegalovirus (CMV) is the most common congenital infection, with approximately 44,000
congenitally infected infants in the U.S. per year. A substantial proportion of these
infants will die or suffer permanent injury as a result of their infection. The severity of
congenital infection is greatest with primary maternal CMV infection. Currently, there is no
proven method of preventing congenital CMV infection, and the approach to primary maternal
CMV infection in the United States is haphazard and ineffective. One small, non-randomized
study suggests that maternal administration of CMV hyperimmune globulin may significantly
reduce the rate of congenital CMV infection following maternal primary infection. The MFMU
CMV Trial will address the primary research question: does maternal administration of CMV
hyperimmune globulin lower the rate of congenital CMV infection among the offspring of women
who have been diagnosed with primary CMV infection during early pregnancy?

The research study is funded by the Eunice Kennedy Shriver National Institutes of Child
Health and Human Development (NICHD). Fourteen medical centers across the country are
participating in this research study. In all, 800 pregnant women who are identified with a
primary CMV infection will be enrolled in this research study. The children of these women
will be evaluated and tested at one and two years of age.

Participant Eligibility


Inclusion Criteria:

- Diagnosis of primary maternal CMV infection on the basis of one of the following:

1. A positive CMV Immunoglobulin M (IgM) antibody and low-avidity maternal CMV
Immunoglobulin G (IgG) antibody screen

2. Evidence of maternal seroconversion with development of CMV IgG antibody
following a prior negative CMV screen

- Gestational age at randomization no later than 23 weeks 6 days based on clinical
information and evaluation of the earliest ultrasound; or no later than 27 weeks 6
days for women with a positive IgM, negative IgG initially screened before 23 weeks
who are rescreened after 2-4 weeks and have evidence of IgG seroconversion.

- Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or
therapeutically) before 14 weeks by project gestational age is acceptable.

Exclusion Criteria:

- Maternal CMV infection pre-dating pregnancy as defined by a high IgG avidity index or
a positive IgG in the presence of a negative IgM.

- Known hypersensitivity to plasma or plasma derived products

- Planned termination of pregnancy

- Known major fetal anomalies or demise

- Maternal Immunoglobulin A (IgA) deficiency

- Planned use of immune globulin, ganciclovir, or valganciclovir

- Maternal renal disease (most recent pre-randomization serum creatinine ≥ 1.4 mg/dL;
all women must have serum creatinine measured during the pregnancy and prior to
randomization)

- Maternal immune impairment (e.g., HIV infection, organ transplant on anti-rejection
medications)

- Findings on pre-randomization ultrasound suggestive of established fetal CMV
infection (cerebral ventriculomegaly, microcephaly, cerebral or intra-abdominal
calcifications, abnormalities of amniotic fluid volume, echogenic bowel or ascites).
Abnormally low amniotic fluid volume is defined as no fluid prior to 14 weeks or
maximum vertical pocket < 2 cm on or after 14 weeks gestation. Abnormally high
amniotic fluid volume is defined as > 10 cm.

- Positive fetal CMV findings from culture (amniotic fluid) or PCR.

- Congenital infection with rubella, syphilis, varicella, parvovirus or toxoplasmosis
diagnosed by serology and ultrasound or amniotic fluid testing.

- Intention of the patient or of the managing obstetricians for the delivery to be
outside a Maternal-Fetal Medicine Units Network (MFMU) Network center

- Participation in another interventional study that influences fetal or neonatal death

- Unwilling or unable to commit to 2 year follow-up of the infant