A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- The George Washington University Biostatistics Center
- Enrollment
- 399
- Locations
- 16
- Primary Endpoint
- Number of Participants With the Composite Primary Outcome
Overview
Brief 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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Diagnosis of primary maternal CMV infection on the basis of one of the following:
- •A positive CMV Immunoglobulin M (IgM) antibody and low-avidity maternal CMV Immunoglobulin G (IgG) antibody screen
- •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.
Arms & Interventions
CMV hyperimmune globulin - Cytogam®
Infusion of Cytogam®, Cytomegalovirus Immune Globulin Intravenous (Human) (CMV-IGIV)
Intervention: CMV hyperimmune globulin (Drug)
Placebo
IV 5% albumin diluted 1 to 9 with 5% Dextrose in water (D5W)
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Number of Participants With the Composite Primary Outcome
Time Frame: From randomization through 3 weeks of life
The primary outcome is a binary outcome defined by the occurrence or non-occurrence of any of the following vs. none of the following: fetal loss (spontaneous or termination), confirmed fetal CMV infection from amniocentesis, neonatal death before assessment of CMV infection can be made, or neonatal congenital CMV infection. Neonatal congenital CMV infection is diagnosed by urine or saliva collected by 3 weeks of age that is positive for CMV by culture (the intent will be to obtain in the first two days of life). In the event that Polymerase Chain Reaction (PCR) is positive but culture is negative, a repeat culture must be positive by 3 weeks of age.
Number of Participants With a Fetal or Neonatal Death With Proven CMV Infection
Time Frame: From randomization through 3 weeks of life
component of primary composite outcome
Number of Participants Who Had a Fetus or Neonate With CMV Infection
Time Frame: From randomization through 3 weeks of life
Component of composite primary outcome
Number of Participants Who Had a Neonatal Death Without CMV Infection
Time Frame: From randomization through 3 weeks of life
component of composite primary outcome
Number of Participants With Fetal Death Without Proven CMV Infection
Time Frame: From randomization through delivery
component of primary composite outcome
Secondary Outcomes
- Number of Participants Whose Gestational Age at Delivery Was Before 34 Weeks, 0 Days(Delivery before 34 weeks gestation)
- Number of Participants With Placental Abruption(From randomization through delivery (maximum 42 weeks gestation))
- Number of Participants Whose Gestational Age at Delivery Was Before 37 Weeks(Delivery before 37 weeks gestation)
- Number of Neonates With Grade 3 or 4 Intraventricular Hemorrhage(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Number of Participants Reporting Yes or no to Medication Side Effects(From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation))
- Median Neonatal Head Circumference(72 hours postpartum)
- Number of Participants With Symptomatic CMV Infection(During pregnancy up to 3 weeks postpartum)
- Number of Neonates With Retinopathy of Prematurity (ROP)(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Number of Participants With Gestational Hypertension or Preeclampsia(from randomization through discharge from the hospital)
- Median Birth Weight(Delivery)
- Number of Neonates With Ventriculomegaly(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Median Gestational Age at Delivery(Delivery)
- Number of Participants Who Had a Fetal or Neonatal Death(From randomization (10-27 weeks gestation) through delivery (maximum 42 weeks gestation) up to 120 days of life)
- Number of Neonates With Neonatal Pneumonia(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Number of Neonates Experiencing Seizures / Encephalopathy(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Number of Participants With Fetal Growth Restriction(Delivery)
- Number of Neonates With Respiratory Distress Syndrome(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Number of Neonates With Suspected Neonatal Sepsis(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Median Length of Neonatal Hospital Stay(birth to neonatal hospital discharge (usually a maximum of 120 days))
- Number of Children Diagnosed With Chorioretinitis(2 years of age)
- Number of Infants or Children With the Composite Outcome(24 month study exam)
- Failure to Thrive at 24 Months(24 months of age)
- Number of Neonates With Chronic Lung Disease(28 days of life)
- Number of Neonates With Necrotizing Enterocolitis (NEC)(0 days to approximately 120 days of life or hospital discharge, whichever is sooner)
- Number of Neonates With Hyperbilirubinemia(From birth to 1 week of life)
- Number of Participants Experiencing Infant or Child Death(Birth to 24 month study exam)
- Number of Children With Sensorineural Hearing Loss(12 and 24 months corrected age)
- Mean Motor Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)(12 and 24 months corrected age)
- Overall Child Status at 24 Months of Age(24 month study exam)
- Mean Cognitive Composite Scores From the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III)(12 and 24 months corrected age)