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Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial (CONCERT)

This study has been terminated.
(1 Indication for further investigations (brain ultrasound). 2 Change of study design to efficacy study with historical control group.)
Sponsor:
Collaborators:
Stichting Nuts Ohra
Leiden University Medical Center
Information provided by (Responsible Party):
Dr. Ann C.T.M. Vossen, Leiden University
ClinicalTrials.gov Identifier:
NCT01655212
First received: July 13, 2012
Last updated: November 4, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Congenital Cytomegalovirus Infection
Sensorineural Hearing Loss
Drug: Valganciclovir
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Hearing assessment [ Time Frame: 1 year follow-up ] [ Designated as safety issue: No ]
    At 1 year follow-up hearing will be assessed with Brainstem Evoked Response Audiometry at an audiological center.


Secondary Outcome Measures:
  • Child development [ Time Frame: 1 year follow-up ] [ Designated as safety issue: No ]
    At 1 year follow-up child development will be assessed during a home visit with the Bayley Scales of Infant Development III. Additionally, parents will fill in the Dutch Child Development Inventory.

  • Viral load [ Time Frame: Baseline, weekly during 7 weeks, and at 1 year ] [ Designated as safety issue: No ]

    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 1 year).



Enrollment: 2
Study Start Date: June 2012
Estimated Study Completion Date: June 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Infants in the control group receive no antiviral therapy. Counseling and treatment assigned by an audiological center remains unchanged.

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 randomized before the age of 13 weeks to a treatment group (6 weeks valganciclovir 32 mg/kg daily dose; oral solution) or 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 25 infants in each treatment arm have been randomized.

At 1 year follow-up hearing and child development are assessed. Hearing will be assessed with Brainstem Evoked Response Audiometry at an audiological center. Child development will be assessed during a home visit with the Bayley Scales of Infant Development III and parents will fill in the Dutch Child Development Inventory (NCDI) which will give more detailed information on communicative development of their child. 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 RCT 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.

  Eligibility

Ages Eligible for Study:   up to 12 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • ≥ 37 weeks gestational age.
  • Birth weight ≥ 2500 gram.
  • Parental signed informed consent.

Exclusion Criteria:

  • Indications for symptomatic congenital CMV infection based on diagnostics carried out prior to the inclusion of the child in the trial.
  • In case during the house visit the presence of a symptomatic CMV infection is doubted, inclusion will be discussed. Depending on the medical history taking, physical examination and laboratory tests inclusion will be decided upon.
  • Treatment with other antiviral agents or immunoglobulins.
  • Leucopenia < 0,5 x 10*9/L (blood sample tested at t=0).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01655212

Locations
Netherlands
Department Medical Microbiology, Leiden University Medical Center
Leiden, Zuid Holland, Netherlands, 2300 RC
Sponsors and Collaborators
Dr. Ann C.T.M. Vossen
Stichting Nuts Ohra
Leiden University Medical Center
Investigators
Study Director: Ann CT Vossen, Dr. Leiden University Medical Center
Principal Investigator: Anne Marie Oudesluys-Murphy, Prof. Dr. Leiden University Medical Center
  More Information

Additional Information:
Publications:

Responsible Party: Dr. Ann C.T.M. Vossen, MD, PhD, Dept of Medical Microbiology, Leiden University
ClinicalTrials.gov Identifier: NCT01655212     History of Changes
Other Study ID Numbers: CMV-MM-1, 2011-005378-44
Study First Received: July 13, 2012
Last Updated: November 4, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Cytomegalovirus
Congenital infection
Sensorineural hearing loss
Randomized controlled trial
Valganciclovir

Additional relevant MeSH terms:
Cytomegalovirus Infections
Deafness
Hearing Loss
Hearing Loss, Sensorineural
Infection
DNA Virus Infections
Ear Diseases
Hearing Disorders
Herpesviridae Infections
Nervous System Diseases
Neurologic Manifestations
Otorhinolaryngologic Diseases
Sensation Disorders
Signs and Symptoms
Virus Diseases
Antiviral Agents
Ganciclovir
Valganciclovir
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014