Congenital Cytomegalovirus InfectionCHILdNCT03973359
Epidemiology and Prevention of Congenital HCMV in Immune Mothers. Congenital HCMV Infection Lombardy
A study testing Hygienic recommendations in people with Congenital Cytomegalovirus Infection and Maternal Cytomegalovirus Infection, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 12 sites in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Congenital Cytomegalovirus Infection, Maternal Cytomegalovirus Infection
- What is being tested?
- Hygienic recommendations
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23,500 participants
- Where
- 12 sitesItaly
- Study dates
- 4 Sep 2017to Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Unreliable women as judged by the investigator
- Women not willing to give written consent
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Italy12 sites, 11 recruiting
- Recruiting
ASST Spedali Civili di Brescia
Brescia, 25123
Federico Prefumo, MD
- Recruiting
Poliambulanza Brescia
Brescia, 25124
Giorgio Pagani, MD
- Recruiting
ASST Vimercate (Ospedale di Carate Brianza)
Carate Brianza, 20841
Anna Locatelli, MD
- Recruiting
ASST Monza (presidio di Desio)
Desio, 20832
Simona Rutolo, MD
- Recruiting
Fondazione IRCCS Ospedale Maggiore Policlinico
Milan, 20122
Beatrice Tassis, MD
- Recruiting
Ospedale Macedonio Melloni (ASST FBF-Sacco)
Milan, 20129
Michele Vignali, MD
- Recruiting
Ospedale San Raffaele
Milan, 20132
Paolo Cavoretto, MD
- Recruiting
Ospedale Buzzi (ASST FBF-Sacco)
Milan, 20154
Irene Cetin, MD
- Recruiting
Ospedale Sacco (ASST FBF-Sacco)
Milan, 20157
Valeria Savasi, MD
- Recruiting
Fondazione Monza Brianza per il Bambino e la sua Mamma
Monza, 20900
Patrizia Vergani, MD
- Recruiting
Fondazione IRCCS Policlinico San Matteo
Pavia
Arsenio Spinillo, MD
- Active, not recruiting
ASST dei Sette Laghi (Ospedale Filippo Del Ponte)
Varese, 21100
About this study
Official title: 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.
Read the 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).
- Being tested
- Hygienic recommendations
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hygienic recommendationsBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| Epidemiology | No intervention | HCMV-seropositive pregnant women receiving standard care |
| Prevention | Experimental | HCMV-seropositive pregnant women receiving hygienic information Receives: Behavioral: Hygienic recommendations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1. Epidemiology study. Incidence and clinical outcome of congenital HCMV infection in pregnant women with preconception immunity.
Number of infants with ascertained congenital infection.
Measured: Within 21 days of life
Part 2. Prevention study. Efficacy of hygiene counseling in reducing congenital HCMV infection in pregnant women with preconception immunity.
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.
Measured: Within 21 days of life
Secondary outcomes (11)
Frequency of non-primary infections during pregnancy (Nested study)
Number of participants with HCMV non-primary infection. HCMV non-primary infection is defined as detection of HCMV DNA shedding in bodily fluids.
Measured: 10, 20, 30, 40 gestation weeks
Frequency of HCMV re-infections vs re-activations during pregnancy (Nested study)
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.
Measured: 10, 20, 30, 40 gestation weeks
Antigen-specific IgG levels in non-primary infection during pregnancy (Nested study)
Levels of antigen-specific IgG in participants with or w/o non-primary infection.
Measured: 10, 20, 30, 40 gestation weeks
Antigen-specific IgM levels in non-primary infection during pregnancy (Nested study)
Levels of antigen-specific IgM in participants with or w/o non-primary infection.
Measured: 10, 20, 30, 40 gestation weeks
Neutralizing antibody titers in non-primary infection during pregnancy (Nested study)
Titers of neutralizing antibodies in participants with or w/o non-primary infection.
Measured: 10, 20, 30, 40 gestation weeks
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Age
Age in mothers of newborns with or w/o congenital HCMV infection
Measured: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Country of origin
Country of origin of mothers of newborns with or w/o congenital HCMV infection
Measured: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Occupation
Occupation of mothers of newborns with or w/o congenital HCM infection
Measured: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Contact with young children
Contact with children <36 months in mothers of newborns with or w/o congenital HCMV infection
Measured: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Twin pregnancy
Twin vs singleton pregnancy in mothers of newborns with or w/o congenital HCMV infection
Measured: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Concomitant pathologies
Concomitant pathologies in mothers of newborns with or w/o congenital HCMV infection
Measured: Delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start4 Sep 2017
- Primary completionJul 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congenital Cytomegalovirus InfectionStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 23,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione Regionale per la Ricerca Biomedica
- Responsible party
- Principal investigator, Daniele Lilleri, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Daniele Lilleri, MD, Principal investigator, Fondazione IRCCS Policlinico San Matteo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03973359
- Sponsor's protocol ID
- 20170011101
- Acronym
- CHILd
- Status last verified
- May 2019
- First submitted
- 20 May 2019
- Last updated
- 4 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lilleri D, Tassis B, Pugni L, Ronchi A, Pietrasanta C, Spinillo A, Arossa A, Achille C, Vergani P, Ornaghi S, Riboni S, Cavoretto P, Candiani M, Gaeta G, Prefumo F, Fratelli N, Fichera A, Vignali M, Barbasetti Di Prun A, Fabbri E, Cetin I, Locatelli A, Consonni S, Rutolo S, Miotto E, Savasi V, Di Giminiani M, Cromi A, Binda S, Fiorina L, Furione M, Cassinelli G, Klersy C; CHILd Study Group. Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study). Clin Infect Dis. 2023 Feb 8;76(3):513-520. doi: 10.1093/cid/ciac482.
PubMed 35717635
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incidence, Outcome and Prevention of Congenital Human Cytomegalovirus (HCMV) Infection in HCMV-seropositive Pregnant Women
- ClinicalTrials.gov ID
- NCT03973359
- Acronym / sponsor ID
- CHILd / 20170011101
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 23,500 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Collaborators
- Fondazione Regionale per la Ricerca Biomedica
- Study start
- 4 Sep 2017 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 4 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Epidemiology | No intervention | –HCMV-seropositive pregnant women receiving standard care |
| Prevention | Experimental | Behavioral: Hygienic recommendationsHCMV-seropositive pregnant women receiving hygienic information |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- Unreliable women as judged by the investigator
- Women not willing to give written consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hygienic recommendationsRecommendation 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. | Behavioural | Prevention |
Primary outcome
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.
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.
11 secondary outcomes
Frequency of non-primary infections during pregnancy (Nested study)
Time frame: 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
Antigen-specific IgG levels in non-primary infection during pregnancy (Nested study)
Time frame: 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
Neutralizing antibody titers in non-primary infection during pregnancy (Nested study)
Time frame: 10, 20, 30, 40 gestation weeks
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Age
Time frame: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Country of origin
Time frame: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Occupation
Time frame: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Contact with young children
Time frame: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Twin pregnancy
Time frame: Delivery
Risk factors for congenital HCMV infection in pregnant women with preconception immunity. Concomitant pathologies
Time frame: Delivery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2019.
- Derived from this study: PubMed 35717635Lilleri D, Tassis B, Pugni L, Ronchi A, Pietrasanta C, Spinillo A, Arossa A, Achille C, Vergani P, Ornaghi S, Riboni S, Cavoretto P, Candiani M, Gaeta G, Prefumo F, Fratelli N, Fichera A, Vignali M, Barbasetti Di Prun A, Fabbri E, Cetin I, Locatelli A, Consonni S, Rutolo S, Miotto E, Savasi V, Di Giminiani M, Cromi A, Binda S, Fiorina L, Furione M, Cassinelli G, Klersy C; CHILd Study Group. Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study). Clin Infect Dis. 2023 Feb 8;76(3):513-520. doi: 10.1093/cid/ciac482.
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Cytomegalovirus Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniele Lilleri, MD principal investigator
Fondazione IRCCS Policlinico San Matteo
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hygienic recommendations in people with Congenital Cytomegalovirus Infection and Maternal Cytomegalovirus Infection, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 12 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Daniele Lilleri, MD (+39 0382 501501, d.lilleri@smatteo.pv.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03973359, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2019.