Congenital Cytomegalovirus: Efficacy of Antiviral Treatment

NCT02005822 | Completed Phase 3 DMC

• 2 other identifiers: CMV-MM-22013-003068-30
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Cytomegalovirus Infection; Sensorineural Hearing Loss

Keywords

Cytomegalovirus; Congenital infection; Sensorineural hearing loss; Valganciclovir

Outcome Measures

Primary Outcomes (1)

• Hearing assessment

  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 Outcomes (2)

• Child development

  Age: 20 months

• Viral load

  Baseline, weekly during 7 weeks, and at 20 months of age

Study Arms (2)

Valganciclovir

EXPERIMENTAL

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

Drug: Valganciclovir

Control

NO INTERVENTION

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.

Interventions

Valganciclovir DRUG

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

Also known as: Valcyte, Valganciclovirhydrochloride

Valganciclovir

Eligibility Criteria

• Age: 3 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dr. Ann C.T.M. Vossen: lead
• Stichting Nuts Ohra: collaborator
• Leiden University Medical Center: collaborator

Study Sites (1)

Department Medical Microbiology

Leiden, South Holland, 2300 RC, Netherlands

Location

Related Publications (16)

• 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.

  PMID: 12915819 BACKGROUND

• 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.

  PMID: 20232081 BACKGROUND

• 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.

  PMID: 18588736 BACKGROUND

• 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.

  PMID: 12799506 BACKGROUND

• 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.

  PMID: 8301446 BACKGROUND

• 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.

  PMID: 9129069 BACKGROUND

• 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.

  PMID: 16786362 BACKGROUND

• 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.

  PMID: 18571542 BACKGROUND

• 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.

  PMID: 21837795 BACKGROUND

• 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.

  PMID: 19836301 BACKGROUND

• 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.

  PMID: 9108862 BACKGROUND

• 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.

  PMID: 16326692 BACKGROUND

• 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.

  PMID: 20807160 BACKGROUND

• 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.

  PMID: 21242546 BACKGROUND

• 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.

  PMID: 18279073 BACKGROUND

• 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.

  PMID: 41026887 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Hearing Loss, Sensorineural

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ann CTM Vossen, Dr.

  Leiden University Medical Center

  STUDY DIRECTOR

• Anne Marie Oudesluys - Murphy, Prof. Dr.

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Dept of Medical Microbiology

Study Record Dates

• First Submitted: December 4, 2013
• First Posted: December 9, 2013
• Study Start: October 22, 2013
• Primary Completion: May 17, 2018
• Study Completion: May 17, 2018
• Last Updated: June 3, 2021

Record last verified: 2021-06

Locations

NL (1)