A Randomized Trial to Prevent Congenital Cytomegalovirus (CMV)
The study is a randomized double-masked placebo controlled multi-center clinical trial of women at participating MFMu network clinical centers. Women with evidence of primary CMV infection before 23 weeks' gestation will be randomized to one of two monthly treatments:
* iV CMV hyperimmune globulin at a dose of 100mg/kg current body weight
* identical appearing placebo consisting of iV albumin 5% diluted in a solution of dextrose in water, (with matching volume). albumin allows the placebo to have a [Quote]foamy[Quote] appearance similar to the active drug.
Consenting women will be assigned to one of the two treatment groups by the center's pharmacist, who is not masked, according to a randomization sequence prepared and maintained centrally by the Biostatistical Coordinating Center (BCC). The active and placebo study medication will be prepared at the center's pharmacy according to the randomization sequence. The study is double masked; neither the patient nor the clinical staff will be aware of the treatment assignment.
The simple urn method will be used to generate the randomization sequences because it provides a high probability of balance in treatment assignments, it is unpredictable, and it allows an explicit randomization analysis to be conducted with relative ease. Randomization will be stratified by clinical site to assure balance between the two treatment groups with respect to anticipated differences in the clinic populations and possible differences in patient management.
The primary outcome is defined as 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. Please see protocol pages 14-16 for additional maternal, fetal, neonatal, infant and child secondary outcomes.
1. Diagnosis of primary maternal CMV infection on the basis of one of the following:
A positive CMV IgM antibody (greater than or equal to 1.00 index) and low-avidity maternal CMV IgG antibody screen (less than 50%)
Evidence of maternal seroconversion with development of CMV IgG antibody (greater than or equal to 6.0 AU/ml) following a prior negative CMV screen (less than 6.0 AU/ml)
2. Gestational age at randomization no later than 23.6 weeks based on clinical information and evaluation of the earliest ultrasound; or no later than 27.6 weeks for women with a positive IgM, negative IgG initially screened before 23 weeks who are rescreened after 2 weeks and have evidence of IgG seroconversion. Additionally, randomization must occur within six weeks of the blood draw for the qualifying screening sample.
3. Singleton pregnancy. A twin pregnancy reduced to singleton (either spontaneously or therapeutically) before 14.0 weeks by project gestational age is acceptable.
4. Age 16 and older.