Clinical trial NCT00881517: Efficacy Study of Human Cytomegalovirus (HCMV) Hyperimmune Globulin to Prevent Congenital HCMV Infection
Official title: Prevention of Human Cytomegalovirus (HCMV) Mother-to-fetus Transmission by Administration of Virus-specific Hyperimmune Globulin to Pregnant Women With Primary HCMV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Cytomegalovirus Infection
Keywords: human cytomegalovirus
immune globulin
congenital infection
prevention
pregnancy
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2009-04-15
Enrollment: 124
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evidence of congenital HCMV infection in the fetus/newborn
timeFrame: At amniocentesis and/or within one week after birth
Secondary outcomes:
measure: HCMV-specific immune response (humoral and cell-mediated)
timeFrame: 36-48 months
measure: Virological and histological findings in placentas
timeFrame: 36-48 months
measure: Clinical outcome of newborns with congenital HCMV infection
timeFrame: within 2 weeks after birth
measure: Safety of Cytotect in the mother and newborn
timeFrame: within 24 hours after delivery
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Dipartimento di Ostetricia e Ginecologia, Ospedali Riuniti
city: Bologna
country: Italy
facility: Medicina dell'Età Prenatale, Ospedale Policlinico S.Orsola
city: Brescia
country: Italy
facility: Medicina Materno-Fetale, Spedali Civili
city: Genova
country: Italy
facility: UOC Malattie Infettive, IRCCS Istituto G.Gaslini
city: Milano
country: Italy
facility: Dipartimento per la salute della donna, del bambino e del neonato. Ospedale Maggiore Policlinico Mangiagalli e Regina Elena
city: Milano
country: Italy
facility: Ostetricia e Ginecologia, Ospedale V.Buzzi
city: Milano
country: Italy
facility: Struttura Semplice di Ostetricia, Ospedale Niguarda Cà Granda
city: Monza
country: Italy
facility: Clinica Ostetrica e Ginecologica, Ospedale S. Gerardo
city: Pavia
country: Italy
facility: Ostetricia e Ginecologia, Fondazione IRCCS Policlinico San Matteo
city: Torino
country: Italy
facility: SCDU Ostetricia e Ginecologia a indirizzo materno fetale, Dipartimento di Discipline Ginecologiche e Ostetriche, Università di Torino
city: Trieste
country: Italy
facility: Dipartimento di Ostetricia e Ginecologia, IRCCS Burlo Garofolo
Study officials:
affiliation: SC Ostetricia e Ginecologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
name: Maria Grazia Revello, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Revello MG, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A, Guaschino S, Vergani P, Todros T, Frusca T, Arossa A, Furione M, Rognoni V, Rizzo N, Gabrielli L, Klersy C, Gerna G; CHIP Study Group. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med. 2014 Apr 3;370(14):1316-26. doi: 10.1056/NEJMoa1310214.