Efficacy Study of Human Cytomegalovirus (HCMV) Hyperimmune Globulin to Prevent Congenital HCMV Infection (CHIP)

• HCMV-specific immune response (humoral and cell-mediated) [ Time Frame: 36-48 months ] [ Designated as safety issue: No ]
• Virological and histological findings in placentas [ Time Frame: 36-48 months ] [ Designated as safety issue: No ]
• Clinical outcome of newborns with congenital HCMV infection [ Time Frame: within 2 weeks after birth ] [ Designated as safety issue: No ]
• Safety of Cytotect in the mother and newborn [ Time Frame: within 24 hours after delivery ] [ Designated as safety issue: Yes ]

The aim of this trial is to verify, under controlled conditions, the reported efficacy of human cytomegalovirus (HCMV)-specific hyperimmune globulin administration to pregnant women suffering from primary HCMV infection for the prevention of intrauterine HCMV transmission.

HCMV is the leading infectious cause of mental retardation and deafness in infants with congenital HCMV infection. Primary HCMV infections during pregnancy carry the highest risk of fetal infection and disease. No intervention of proven efficacy is available in case of primary HCMV infection in pregnancy. However, a study published in 2005 (Nigro et al., NEJM 353:1350-62, 2005) reported that in pregnant women with primary HCMV infection treated with HCMV-specific hyperimmune globulin (Cytotect®, Biotest) the risk of transmitting the infection to the fetus was reduced from 40% to 16%. Unfortunately, since the study was conducted with inadequate controls, the actual efficacy of hyperimmune globulin could not be properly assessed.

In the present randomized, double-blind, placebo-controlled, multicenter trial pregnant women with ascertained primary HCMV infection at 4-26 weeks of gestation will be randomized to receive Cytotect® or placebo intravenously within 6 weeks after the presumed onset of infection.

Primary efficacy parameter will be the number of HCMV-infected newborns or fetuses.

• Drug: HCMV-specific hyperimmune globulin (Cytotect®)
  100U (2.0ml)/Kg i.v. every 4 weeks up to 38 weeks' gestation or HCMV-positive amniocentesis or pregnancy termination.
  Other Name: Cytotect®
• Drug: Isotonic solution of sodium chloride (placebo)
  2.0ml/Kg i.v. every 4 weeks until 38 weeks'gestation or HCMV-positive amniocentesis or pregnancy termination

• Experimental: Cytotect
  Intervention: Drug: HCMV-specific hyperimmune globulin (Cytotect®)
• Placebo Comparator: placebo
  Intervention: Drug: Isotonic solution of sodium chloride (placebo)

Inclusion Criteria:

• pregnant women (in vitro fertilization permitted)
• >= 18 years of age
• primary HCMV infection at 5-26 weeks' gestation
• <= 6 weeks from presumed onset of infection
• gestational age between 5-32 weeks' gestation
• written informed consent

Exclusion Criteria:

• multiple pregnancy
• history of HIV or HBV or HCV infection
• known immunodeficiency or immunosuppression
• congenital or acquired autoimmune disease
• known intolerance to protein of human origin
• known intolerance to immune globulin
• history of adverse effects to vaccination
• hypersensitivity to human immune globulin (pathological IgG or IgA deficiences)
• renal failure
• serious organic or psychiatric disease
• lack of motivation to participate in the study
• women unable to satisfy study requirements
• women not willing or unable to provide written informed consent
• women not willing to give consent to transmission of anonymised data