Epidemiology and Prevention of Congenital HCMV in Immune Mothers. Congenital HCMV Infection Lombardy (CHILd)

May 31, 2019 updated by: Daniele Lilleri, Foundation IRCCS San Matteo Hospital

Incidence, Outcome and Prevention of Congenital Human Cytomegalovirus (HCMV) Infection in HCMV-seropositive Pregnant Women

Human cytomegalovirus (HCMV) is the leading infectious agent causing congenital disabilities such as mental retardation, psychomotor delay, hearing loss, speech and language disabilities, behavioural disorders and visual impairment. About 0.6% newborns are HCMV-congenitally infected and, among these, about 20% are symptomatic at birth or will develop long-term sequelae. The public health impact of congenital HCMV is substantial although greatly unrecognized. In Italy, estimated direct costs per affected child exceed €100.000 for a total of €60-70M. HCMV is also a significant cause of infection/disease in the immunocompromised host.

Epidemiological studies and population-based models have preliminarily documented that most of the burden associated to congenital HCMV would be due to non-primary maternal infection. Presently, reinfections are believed to be responsible for the great majority of infected fetuses born to immune mothers.

This study addresses incidence, outcome and prevention of congenital HCMV infection in seropositive pregnant women.The study includes 2 parts: part 1 in which the incidence and outcome of congenital HCMV is investigated in a large population of HCMV seropositive pregnant women and HCMV shedding and immune response is closely monitored in a subset of participants (nested study); part 2 in which the efficacy of an hygiene intervention is assessed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Part 1. Epidemiologic study. To investigate incidence and outcome of congenital infection in immune mothers, clinical records of pregnant women are reviewed for HCMV serostatus at ≤ 13 weeks' gestation. Women with HCMV serology compatible with a remote infection are asked to participate in the study. Consenting women are given a pre-stamped, pre-addressed envelope containing a swab to collect newborn's saliva. Envelopes are sent by courier to a centralized diagnostic facility for HCMV testing.

Women can also be enrolled at delivery, provided that the woman has records of presence of virus-specific IgG and absence of IgM early during gestation(or in a previous pregnancy) or, in case of unknown serostatus, a sample of serum/plasma stored at ≤ 13 weeks' gestation is available for retrospective antibody testing (retrospective part of the epidemiology study).

Part 1. Nested study. A subset of IgG pos IgM neg women selected among those enrolled at ≤13 weeks' gestation in the epidemiology study are included in a nested study. These women are monitored at enrolment, 20, 30 weeks of gestation and at delivery by prospective determination of HCMV DNA excretion in different bodily fluids. In DNA-positive specimens selected HCMV genes will be sequenced.

Part 2. Prevention study. To assess the effectiveness of hygiene measures for prevention of congenital infection HCMV seropositive pregnant women are enrolled at ≤ 13 weeks' gestation. Part 2 starts when enrolment of Part 1 is completed. In practice, part 2 is a continuation of part 1 with the only addition of delivering hygiene information at enrolment.

Part 2 will not be performed in case congenital infection rate in Part 1 is <0.4% and clear maternal risk factor for intrauterine transmission cannot be identified at interim analysis (i.e. after examination of 5000 newborns).

In case HCMV DNA is detected in newborn's saliva, a urine sample is obtained for confirmation of congenital infection. Infants with documented congenital infection are clinically assessed at the time of diagnosis (for Part 1 and 2) and at one year of age (Part 1 only).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
23500

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Brescia, Italy, 25123
        • Recruiting
        • ASST Spedali Civili di Brescia
        • Contact:
          • Federico Prefumo, MD
      • Brescia, Italy, 25124
        • Recruiting
        • Poliambulanza Brescia
        • Contact:
          • Giorgio Pagani, MD
      • Carate Brianza, Italy, 20841
        • Recruiting
        • ASST Vimercate (Ospedale di Carate Brianza)
        • Contact:
          • Anna Locatelli, MD
      • Desio, Italy, 20832
        • Recruiting
        • ASST Monza (presidio di Desio)
        • Contact:
          • Simona Rutolo, MD
      • Milan, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele
        • Contact:
          • Paolo Cavoretto, MD
      • Milan, Italy, 20122
        • Recruiting
        • Fondazione IRCCS Ospedale Maggiore Policlinico
        • Contact:
          • Beatrice Tassis, MD
      • Milan, Italy, 20129
        • Recruiting
        • Ospedale Macedonio Melloni (ASST FBF-Sacco)
        • Contact:
          • Michele Vignali, MD
      • Milan, Italy, 20154
        • Recruiting
        • Ospedale Buzzi (ASST FBF-Sacco)
        • Contact:
          • Irene Cetin, MD
      • Milan, Italy, 20157
        • Recruiting
        • Ospedale Sacco (ASST FBF-Sacco)
        • Contact:
          • Valeria Savasi, MD
      • Monza, Italy, 20900
        • Recruiting
        • Fondazione Monza Brianza per il Bambino e la sua Mamma
        • Contact:
          • Patrizia Vergani, MD
      • Pavia, Italy
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo
        • Contact:
          • Arsenio Spinillo, MD
      • Varese, Italy, 21100
        • Active, not recruiting
        • ASST dei Sette Laghi (Ospedale Filippo Del Ponte)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Adult (≥ 18 years old) pregnant women at ≤13 weeks gestation
  • Presence of HCMV IgG and absence of IgM or presence of high avidity IgG with or without IgM
  • Presence of HCMV-specific IgG and absence of IgM or presence of high avidity IgG in case of positive IgM at ≤13 weeks gestation documented by medical report or by retrospective antibody determination on samples stored at ≤13 weeks (for women enrolled at delivery)
  • Willingness to participate in the study
  • Ability to understand information material
  • Written informed consent

Exclusion Criteria:

  • Unreliable women as judged by the investigator
  • Women not willing to give written consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Epidemiology
HCMV-seropositive pregnant women receiving standard care
Experimental: Prevention
HCMV-seropositive pregnant women receiving hygienic information
Behavioral: Hygienic recommendations
Recommendation of protective behaviours such as frequent hand washing and avoiding risky behaviours such as kissing young children on the mouth or cheeks and sharing utensils, foods etc.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1. Epidemiology study. Incidence and clinical outcome of congenital HCMV infection in pregnant women with preconception immunity.
Time Frame: Within 21 days of life
Number of infants with ascertained congenital infection.
Within 21 days of life
Part 2. Prevention study. Efficacy of hygiene counseling in reducing congenital HCMV infection in pregnant women with preconception immunity.
Time Frame: Within 21 days of life
Number of infants with ascertained congenital infection born to HCMV seropositive women informed about hygiene measures compared to the number of newborns with congenital infection diagnosed in Part 1.
Within 21 days of life

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Frequency of non-primary infections during pregnancy (Nested study)
Time Frame: 10, 20, 30, 40 gestation weeks
Number of participants with HCMV non-primary infection. HCMV non-primary infection is defined as detection of HCMV DNA shedding in bodily fluids.
10, 20, 30, 40 gestation weeks
Frequency of HCMV re-infections vs re-activations during pregnancy (Nested study)
Time Frame: 10, 20, 30, 40 gestation weeks
Number of participants with HCMV re-infection or re-activation. Re-infection is defined as the appearance of genetically distinct HCMV strains; Reactivation is defined as the sustained presence of the same strain.
10, 20, 30, 40 gestation weeks
Antigen-specific IgG levels in non-primary infection during pregnancy (Nested study)
Time Frame: 10, 20, 30, 40 gestation weeks
Levels of antigen-specific IgG in participants with or w/o non-primary infection.
10, 20, 30, 40 gestation weeks
Antigen-specific IgM levels in non-primary infection during pregnancy (Nested study)
Time Frame: 10, 20, 30, 40 gestation weeks
Levels of antigen-specific IgM in participants with or w/o non-primary infection.
10, 20, 30, 40 gestation weeks
Neutralizing antibody titers in non-primary infection during pregnancy (Nested study)
Time Frame: 10, 20, 30, 40 gestation weeks
Titers of neutralizing antibodies in participants with or w/o non-primary infection.
10, 20, 30, 40 gestation weeks
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Age
Time Frame: Delivery
Age in mothers of newborns with or w/o congenital HCMV infection
Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Country of origin
Time Frame: Delivery
Country of origin of mothers of newborns with or w/o congenital HCMV infection
Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Occupation
Time Frame: Delivery
Occupation of mothers of newborns with or w/o congenital HCM infection
Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Contact with young children
Time Frame: Delivery
Contact with children <36 months in mothers of newborns with or w/o congenital HCMV infection
Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Twin pregnancy
Time Frame: Delivery
Twin vs singleton pregnancy in mothers of newborns with or w/o congenital HCMV infection
Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Concomitant pathologies
Time Frame: Delivery
Concomitant pathologies in mothers of newborns with or w/o congenital HCMV infection
Delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Foundation IRCCS San Matteo Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Fondazione Regionale per la Ricerca Biomedica (FRRB) - Regione Lombardia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Daniele Lilleri, MD, Fondazione IRCCS Policlinico San Matteo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 4, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 20, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 4, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20170011101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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