Congenital Cytomegalovirus: Efficacy of Antiviral Treatment

NCT ID: NCT02005822

Last Updated: 2021-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-22

Study Completion Date

2018-05-17

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Congenital Cytomegalovirus Infection Sensorineural Hearing Loss

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Valganciclovir

Valganciclovir 32 mg/kg per day in two doses (16 mg/kg per dose) during 6 weeks in an oral solution.

Group Type EXPERIMENTAL

Valganciclovir

Intervention Type DRUG

Infants will be treated with valganciclovir for 6 weeks, 32 mg/kg daily dose in two doses, oral solution.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Valganciclovir

Infants will be treated with valganciclovir for 6 weeks, 32 mg/kg daily dose in two doses, oral solution.

Intervention Type DRUG

Other Intervention Names

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Valcyte Valganciclovirhydrochloride

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

3 Weeks

Maximum Eligible Age

12 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stichting Nuts Ohra

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

Dr. Ann C.T.M. Vossen

OTHER

Sponsor Role lead

Responsible Party

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Dr. Ann C.T.M. Vossen

MD, PhD, Dept of Medical Microbiology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Ann CTM Vossen, Dr.

Role: STUDY_DIRECTOR

Leiden University Medical Center

Anne Marie Oudesluys - Murphy, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

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Department Medical Microbiology

Leiden, South Holland, Netherlands

Site Status

Countries

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Netherlands

References

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Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, Jacobs RF, Vaudry W, Pass RF, Kiell JM, Soong SJ, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003 Jul;143(1):16-25. doi: 10.1016/s0022-3476(03)00192-6.

Reference Type BACKGROUND
PMID: 12915819 (View on PubMed)

Amir J, Wolf DG, Levy I. Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir. Eur J Pediatr. 2010 Sep;169(9):1061-7. doi: 10.1007/s00431-010-1176-9. Epub 2010 Mar 16.

Reference Type BACKGROUND
PMID: 20232081 (View on PubMed)

Lackner A, Acham A, Alborno T, Moser M, Engele H, Raggam RB, Halwachs-Baumann G, Kapitan M, Walch C. Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up. J Laryngol Otol. 2009 Apr;123(4):391-6. doi: 10.1017/S0022215108003162. Epub 2008 Jun 30.

Reference Type BACKGROUND
PMID: 18588736 (View on PubMed)

Michaels MG, Greenberg DP, Sabo DL, Wald ER. Treatment of children with congenital cytomegalovirus infection with ganciclovir. Pediatr Infect Dis J. 2003 Jun;22(6):504-9. doi: 10.1097/01.inf.0000069767.43169.2d.

Reference Type BACKGROUND
PMID: 12799506 (View on PubMed)

Nigro G, Scholz H, Bartmann U. Ganciclovir therapy for symptomatic congenital cytomegalovirus infection in infants: a two-regimen experience. J Pediatr. 1994 Feb;124(2):318-22. doi: 10.1016/s0022-3476(94)70327-2.

Reference Type BACKGROUND
PMID: 8301446 (View on PubMed)

Whitley RJ, Cloud G, Gruber W, Storch GA, Demmler GJ, Jacobs RF, Dankner W, Spector SA, Starr S, Pass RF, Stagno S, Britt WJ, Alford C Jr, Soong S, Zhou XJ, Sherrill L, FitzGerald JM, Sommadossi JP. Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis. 1997 May;175(5):1080-6. doi: 10.1086/516445.

Reference Type BACKGROUND
PMID: 9129069 (View on PubMed)

Smets K, De Coen K, Dhooge I, Standaert L, Laroche S, Mahieu L, Logghe N, Cossey V, Boudewyns A. Selecting neonates with congenital cytomegalovirus infection for ganciclovir therapy. Eur J Pediatr. 2006 Dec;165(12):885-90. doi: 10.1007/s00431-006-0192-2. Epub 2006 Jun 20.

Reference Type BACKGROUND
PMID: 16786362 (View on PubMed)

Foulon I, Naessens A, Foulon W, Casteels A, Gordts F. A 10-year prospective study of sensorineural hearing loss in children with congenital cytomegalovirus infection. J Pediatr. 2008 Jul;153(1):84-8. doi: 10.1016/j.jpeds.2007.12.049. Epub 2008 Mar 6.

Reference Type BACKGROUND
PMID: 18571542 (View on PubMed)

de Vries JJ, Korver AM, Verkerk PH, Rusman L, Claas EC, Loeber JG, Kroes AC, Vossen AC. Congenital cytomegalovirus infection in the Netherlands: birth prevalence and risk factors. J Med Virol. 2011 Oct;83(10):1777-82. doi: 10.1002/jmv.22181.

Reference Type BACKGROUND
PMID: 21837795 (View on PubMed)

Korver AM, de Vries JJ, Konings S, de Jong JW, Dekker FW, Vossen AC, Frijns JH, Oudesluys-Murphy AM; DECIBEL collaborative study group. DECIBEL study: Congenital cytomegalovirus infection in young children with permanent bilateral hearing impairment in the Netherlands. J Clin Virol. 2009 Dec;46 Suppl 4:S27-31. doi: 10.1016/j.jcv.2009.09.007.

Reference Type BACKGROUND
PMID: 19836301 (View on PubMed)

Fowler KB, McCollister FP, Dahle AJ, Boppana S, Britt WJ, Pass RF. Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital cytomegalovirus infection. J Pediatr. 1997 Apr;130(4):624-30. doi: 10.1016/s0022-3476(97)70248-8.

Reference Type BACKGROUND
PMID: 9108862 (View on PubMed)

Lanari M, Lazzarotto T, Venturi V, Papa I, Gabrielli L, Guerra B, Landini MP, Faldella G. Neonatal cytomegalovirus blood load and risk of sequelae in symptomatic and asymptomatic congenitally infected newborns. Pediatrics. 2006 Jan;117(1):e76-83. doi: 10.1542/peds.2005-0629. Epub 2005 Dec 1.

Reference Type BACKGROUND
PMID: 16326692 (View on PubMed)

Lombardi G, Garofoli F, Stronati M. Congenital cytomegalovirus infection: treatment, sequelae and follow-up. J Matern Fetal Neonatal Med. 2010 Oct;23 Suppl 3:45-8. doi: 10.3109/14767058.2010.506753.

Reference Type BACKGROUND
PMID: 20807160 (View on PubMed)

Misono S, Sie KC, Weiss NS, Huang ML, Boeckh M, Norton SJ, Yueh B. Congenital cytomegalovirus infection in pediatric hearing loss. Arch Otolaryngol Head Neck Surg. 2011 Jan;137(1):47-53. doi: 10.1001/archoto.2010.235.

Reference Type BACKGROUND
PMID: 21242546 (View on PubMed)

Kimberlin DW, Acosta EP, Sanchez PJ, Sood S, Agrawal V, Homans J, Jacobs RF, Lang D, Romero JR, Griffin J, Cloud GA, Lakeman FD, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008 Mar 15;197(6):836-45. doi: 10.1086/528376.

Reference Type BACKGROUND
PMID: 18279073 (View on PubMed)

Schornagel FAJ, Soede W, Vossen ACTM, Oudesluys-Murphy AM. Enhanced auditory brainstem response device (Vivosonic Integrity) in young children, in the child's home and hospital. Int J Audiol. 2025 Sep 30:1-6. doi: 10.1080/14992027.2025.2502441. Online ahead of print.

Reference Type DERIVED
PMID: 41026887 (View on PubMed)

Other Identifiers

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2013-003068-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CMV-MM-2

Identifier Type: -

Identifier Source: org_study_id

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