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

Prevention of Human Cytomegalovirus (HCMV) Mother-to-fetus Transmission by Administration of Virus-specific Hyperimmune Globulin to Pregnant Women With Primary HCMV Infection

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Drug: HCMV-specific hyperimmune globulin (Cytotect®); Drug: Isotonic solution of sodium chloride (placebo)

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 Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evidence of congenital HCMV infection in the fetus/newborn	At amniocentesis and/or within one week after birth

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Matteo
• Investigators: Principal Investigator: Maria Grazia Revello, MD, SC Ostetricia e Ginecologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: April 14, 2009
• First Submitted That Met QC Criteria: April 14, 2009
• First Posted (Estimate): April 15, 2009

Study Record Updates

• Last Update Posted (Estimate): December 8, 2011
• Last Update Submitted That Met QC Criteria: December 7, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: pregnancy; prevention; immune globulin; human cytomegalovirus; congenital infection
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins
• Other Study ID Numbers: FARM7J4HCH