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

Sponsor

IRCCS Policlinico S. Matteo (Other)

Overall Status

Completed

CT.gov ID

NCT00881517

Collaborator

(none)

124

Enrollment

Locations

Arms

Duration (Months)

11.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infection	Drug: HCMV-specific hyperimmune globulin (Cytotect®) Drug: Isotonic solution of sodium chloride (placebo)	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cytotect	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 Names: Cytotect®
Placebo Comparator: placebo	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

Arm

Intervention/Treatment

Experimental: Cytotect

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 Names:

Cytotect®

Placebo Comparator: placebo

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

Outcome Measures

Primary Outcome Measures

Evidence of congenital HCMV infection in the fetus/newborn [At amniocentesis and/or within one week after birth]

Secondary Outcome Measures

HCMV-specific immune response (humoral and cell-mediated) [36-48 months]
Virological and histological findings in placentas [36-48 months]
Clinical outcome of newborns with congenital HCMV infection [within 2 weeks after birth]
Safety of Cytotect in the mother and newborn [within 24 hours after delivery]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Dipartimento di Ostetricia e Ginecologia, Ospedali Riuniti	Bergamo	Italy	24128
2	Medicina dell'Età Prenatale, Ospedale Policlinico S.Orsola	Bologna	Italy	40138
3	Medicina Materno-Fetale, Spedali Civili	Brescia	Italy	25123
4	UOC Malattie Infettive, IRCCS Istituto G.Gaslini	Genova	Italy	16147
5	Dipartimento per la salute della donna, del bambino e del neonato. Ospedale Maggiore Policlinico Mangiagalli e Regina Elena	Milano	Italy	20122
6	Ostetricia e Ginecologia, Ospedale V.Buzzi	Milano	Italy	20154
7	Struttura Semplice di Ostetricia, Ospedale Niguarda Cà Granda	Milano	Italy	20162
8	Clinica Ostetrica e Ginecologica, Ospedale S. Gerardo	Monza	Italy	20052
9	Ostetricia e Ginecologia, Fondazione IRCCS Policlinico San Matteo	Pavia	Italy	27100
10	SCDU Ostetricia e Ginecologia a indirizzo materno fetale, Dipartimento di Discipline Ginecologiche e Ostetriche, Università di Torino	Torino	Italy	10126
11	Dipartimento di Ostetricia e Ginecologia, IRCCS Burlo Garofolo	Trieste	Italy	34137