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

• ClinicalTrials.gov Identifier: NCT00881517
• Recruitment Status: Completed
• First Posted: April 15, 2009
• Last Update Posted: December 8, 2011
• Sponsor: IRCCS Policlinico S. Matteo
• Information provided by (Responsible Party): Maria Grazia Revello, IRCCS Policlinico S. Matteo

Tracking Information

• First Submitted Date: April 14, 2009
• First Posted Date: April 15, 2009
• Last Update Posted Date: December 8, 2011
• Study Start Date: June 2009
• Actual Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 14, 2009): Evidence of congenital HCMV infection in the fetus/newborn [ Time Frame: At amniocentesis and/or within one week after birth ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 14, 2009)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Cytomegalovirus Infection

Intervention

• 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

Study Arms

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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 7, 2011): 124
• Original Estimated Enrollment (submitted: April 14, 2009): 120
• Actual Study Completion Date: October 2011
• Actual Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT00881517
• Other Study ID Numbers: FARM7J4HCH
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Maria Grazia Revello, IRCCS Policlinico S. Matteo
• Study Sponsor: IRCCS Policlinico S. Matteo
• Collaborators: Not Provided

Investigators

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

• PRS Account: IRCCS Policlinico S. Matteo
• Verification Date: December 2011