Congenital Cytomegalovirus: Efficacy of Antiviral Treatment (CONCERT 2)

June 2, 2021 updated by: Dr. Ann C.T.M. Vossen

The Leiden CONCERT Study 2.0 Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Non-Randomized Trial With Historical Control Group

The objective of the trial is to investigate whether early treatment with oral valganciclovir of infants with both congenital cytomegalovirus infection and sensorineural hearing loss can prevent progression of hearing loss.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the Netherlands all neonates are routinely screened for hearing during the first weeks after birth with the Otoacoustic Emissions (OAE) procedure. After the second refer an Automated Auditory Brainstem Response (AABR) is performed. The parents of all newborns, born at ≥ 37 weeks gestational age, that fail this AABR in the Netherlands (about 550 yearly) will be asked for consent for CMV-testing on the dried blood spots. Newborns diagnosed with congenital CMV and with confirmed SNHL (≥ 20 dB) are eligible for inclusion. After informed consent infants will be offered treatment before the age of 13 weeks (6 weeks valganciclovir 32 mg/kg daily dose; oral solution). Parents may decide to participate in the trial in the control group (no antiviral treatment). Infants will be monitored for leucopenia and liver- and kidney function. Inclusion will continue for at least 1.5 years, or until at least 40 infants have been included in the trial.

At age 20 months hearing and child development are assessed in the follow-up. Hearing will be assessed with Brainstem Evoked Response Audiometry with the Vivosonic Integrity. Child development will be assessed with the Bayley Scales of Infant Development III (official Dutch translation) and parents will fill in the Dutch Child Development Inventory (NCDI) which will give more detailed information on communicative development of their child. The hearing assessment and developmental examination will be fulfilled during a home visit. Viral loads in blood and urine will be monitored during antiviral treatment as well as twice in the control group.

This study will provide information on the percentage of infants with a congenital CMV infection who fail the neonatal hearing screening . The trial will show whether early treatment of congenital CMV infected children with hearing impairment prevents deterioration of hearing loss and to what extent. The outcome may lead to implementation of congenital CMV testing in the neonatal hearing screening program or possibly into the newborn blood screening.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • Netherlands
    • Zuid Holland
      • Leiden, Zuid Holland, Netherlands, 2300 RC
        • Department Medical Microbiology

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

Ages Eligible for Study

3 weeks to 2 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria Treatment group and refusal control group

  • Infants with congenital CMV infection, and hearing loss (≥ 20 dB, in one or both ears).
  • Age at time of inclusion is ≤ 12 weeks after birth.
  • Born at ≥ 37 weeks gestational age.
  • Birth weight > -2 SD corrected for duration of pregnancy and ethnic origin.
  • Parental signed informed consent.

Historical control group

  • Infants with congenital CMV infection, and hearing loss (≥ 20 dB, in one or both ears).
  • Age at time of inclusion is > 13 weeks after birth.
  • Born at ≥ 37 weeks gestational age.
  • Birth weight > -2 SD corrected for duration of pregnancy and ethnic origin.
  • Parental signed informed consent.

Exclusion Criteria Treatment group and refusal control group

  • Previously noted (≤ 12 weeks after birth) symptoms possibly related to congenital CMV, for which medical attention was requested. For example: intra uterine growth retardation, petechiae, hepatosplenomegaly, jaundice, microcephaly, thrombocytopenia, elevated transaminases, elevated bilirubin.
  • Treatment with other antiviral agents or immunoglobulins.
  • Solely applicable for treatment group: leucopenia < 0,5 x 10*9/L (blood sample tested at t=0).

Historical control group

  • Previously encountered (≤ 12 weeks after birth) symptoms possibly related to congenital CMV, for which medical attention was requested For example: intra uterine growth retardation, petechiae, hepatosplenomegaly, jaundice, microcephaly, thrombocytopenia, elevated transaminases, elevated bilirubin.
  • Treatment with (val)ganciclovir.
  • Treatment with other antiviral agents or immunoglobulins.

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: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Valganciclovir
Valganciclovir 32 mg/kg per day in two doses (16 mg/kg per dose) during 6 weeks in an oral solution.
Drug: Valganciclovir
Infants will be treated with valganciclovir for 6 weeks, 32 mg/kg daily dose in two doses, oral solution.
Other Names:
  • Valcyte
  • Valganciclovirhydrochloride
No Intervention: Control

Refusal control group:

Infants in the control group receive no antiviral therapy. Counseling and treatment assigned by an audiological center remain unchanged.

Historical control group:

Infants with birth date 1-11-2011 till 1-07-2012 with sensorineural hearing loss and congenital CMV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hearing assessment
Time Frame: Age: 20 months
At 20 months of age hearing will be assessed with Brainstem Evoked Response Audiometry using the Vivosonic Integrity during a home visit.
Age: 20 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Child development
Time Frame: Age: 20 months
At age 20 months child development will be assessed during a home visit with the Bayley Scales of Infant Development III (official Dutch translation). Additionally, parents will fill in the Dutch Child Development Inventory.
Age: 20 months
Viral load
Time Frame: Baseline, weekly during 7 weeks, and at 20 months of age

Viral blood load will be monitored in the treatment group(at baseline, weekly during antiviral treatment, and one week after treatment) as well as in the control group (baseline and 7 weeks after inclusion).

Viral urine load will be monitored in the treatment group and in the control group (at baseline, weekly during 7 weeks after inclusion, and at the age of 20 months).
Baseline, weekly during 7 weeks, and at 20 months of age

Collaborators and Investigators

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

Sponsor

Dr. Ann C.T.M. Vossen

Collaborators

Leiden University Medical Center
Stichting Nuts Ohra

Investigators

  • Study Director: Ann CTM Vossen, Dr., Leiden University Medical Center
  • Principal Investigator: Anne Marie Oudesluys - Murphy, Prof. Dr., Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

October 22, 2013

Primary Completion (Actual)

May 17, 2018

Study Completion (Actual)

May 17, 2018

Study Registration Dates

First Submitted

December 4, 2013

First Submitted That Met QC Criteria

December 4, 2013

First Posted (Estimate)

December 9, 2013

Study Record Updates

Last Update Posted (Actual)

June 3, 2021

Last Update Submitted That Met QC Criteria

June 2, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMV-MM-2
  • 2013-003068-30 (EudraCT Number)

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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