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.

Abstract

Objective: To evaluate the efficacy and safety of ganciclovir therapy in neonates with congenital cytomegalovirus (CMV) disease.

Study design: Neonates with symptomatic CMV disease involving the central nervous system were randomly assigned to receive 6 weeks of intravenous ganciclovir versus no treatment. The primary end point was improved brainstem-evoked response (BSER) between baseline and 6-month follow-up (or, for patients with normal baseline hearing, normal BSER at both time points).

Results: From 1991 to 1999, 100 patients were enrolled. Of these, 42 patients had both a baseline and 6-month follow-up BSER audiometric examination and thus were evaluable for the primary end point. Twenty-one (84%) of 25 ganciclovir recipients had improved hearing or maintained normal hearing between baseline and 6 months versus 10 (59%) of 17 control patients (P=.06). None (0%) of 25 ganciclovir recipients had worsening in hearing between baseline and 6 months versus 7 (41%) of 17 control patients (P<.01). A total of 43 patients had a BSER at both baseline and at 1 year or beyond. Five (21%) of 24 ganciclovir recipients had worsening of hearing between baseline and > or =1 year versus 13 (68%) of 19 control patients (P<.01). A total of 89 patients had absolute neutrophil counts determined during the course of the study; 29 (63%) of 46 ganciclovir-treated patients had grade 3 or 4 neutropenia during treatment versus 9 (21%) of 43 control patients (P<.01).

Conclusions: Ganciclovir therapy begun in the neonatal period in symptomatically infected infants with CMV infection involving the central nervous system prevents hearing deterioration at 6 months and may prevent hearing deterioration at > or =1 year. Almost two thirds of treated infants have significant neutropenia during therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Brain / pathology
  • Calcinosis / epidemiology
  • Calcinosis / pathology
  • Central Nervous System Viral Diseases / congenital*
  • Central Nervous System Viral Diseases / drug therapy*
  • Central Nervous System Viral Diseases / epidemiology
  • Creatinine / metabolism
  • Cytomegalovirus Infections / congenital*
  • Cytomegalovirus Infections / drug therapy*
  • Cytomegalovirus Infections / epidemiology
  • Double-Blind Method
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Female
  • Follow-Up Studies
  • Ganciclovir / adverse effects
  • Ganciclovir / therapeutic use*
  • Hearing Loss, Sensorineural / chemically induced*
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / epidemiology
  • Hepatomegaly / chemically induced
  • Hepatomegaly / epidemiology
  • Humans
  • Hyperbilirubinemia / chemically induced
  • Hyperbilirubinemia / epidemiology
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Male
  • Severity of Illness Index
  • Splenomegaly / chemically induced
  • Splenomegaly / epidemiology
  • Time Factors

Substances

  • Antiviral Agents
  • Creatinine
  • Ganciclovir