A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Condition: Congenital Cytomegalovirus Infection; Maternal Cytomegalovirus Infection
MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections
Intervention: CMV hyperimmune globulin; Placebo
Intervention description: The study's active drug is Cytogam® which is an immunoglobulin G (IgG) containing a standardized amount of antibody to CMV. This drug contains pooled adult human plasma selected for high titers of antibody for CMV, and is administered intravenously at a dose of 100 mg/kg body weight.; The matching placebo consists of AlbuRx® 5% diluted 1:9 with D5W. AlbuRx® 5% contains pooled adult human plasma.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 399.0
Sex: Female
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Perinatology; Cytomegalovirus immune globulin; Cytogam; CMVIG infusions

Summary:

      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.
    

Eligibility criteria:

        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