A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)

The George Washington University Biostatistics Center

Status and phase

Completed

Phase 3

Conditions

Congenital Cytomegalovirus Infection

Maternal Cytomegalovirus Infection

Treatments

Other: Placebo

Drug: CMV hyperimmune globulin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01376778

U10HD053097 (U.S. NIH Grant/Contract)

U10HD068258 (U.S. NIH Grant/Contract)

U10HD034116 (U.S. NIH Grant/Contract)

UG1HD087192 (U.S. NIH Grant/Contract)

U10HD040544 (U.S. NIH Grant/Contract)

U10HD068268 (U.S. NIH Grant/Contract)

UG1HD087230 (U.S. NIH Grant/Contract)

U10HD040545 (U.S. NIH Grant/Contract)

U10HD036801 (U.S. NIH Grant/Contract)

U10HD040500 (U.S. NIH Grant/Contract)

U10HD068282 (U.S. NIH Grant/Contract)

U10HD027915 (U.S. NIH Grant/Contract)

U10HD027869 (U.S. NIH Grant/Contract)

U10HD034208 (U.S. NIH Grant/Contract)

U10HD040560 (U.S. NIH Grant/Contract)

HD36801-CMV

U10HD040512 (U.S. NIH Grant/Contract)

U10HD040485 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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). Sixteen 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.

Enrollment

399 patients

Sex

Female

Volunteers

Accepts Healthy Volunteers

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