Short-Term vs. Long-Term Valganciclovir Therapy for Symptomatic Congenital CMV Infections

NCT00466817 | Completed Phase 3 Results

• 2 other identifiers: 06-0046CASG 112
• Study Type: interventional
• Target: 109
• Locations: 2 countries
• Sites: 48

Brief Summary

Cytomegalovirus (CMV) infection is known to cause hearing loss and mental retardation. The purpose of this study is to compare a 6-week course to a 6-month course of the drug valganciclovir in babies born with CMV to assess the safety and efficacy of this treatment. Participants will include 104 infants (30 days old or younger) born with CMV disease. All infants will take valganciclovir by mouth for 6 weeks. At the end of the 6 week period, subjects will be assigned by chance to receive either valganciclovir or placebo (inactive substance) to complete the 6 months of antiviral treatment. Patients will be followed for the study related evaluations of safety, changes to hearing, and developmental milestones for up to 2 years. Patients will be followed by telephone contact for an additional 3 years. Thus, participants may be involved in study related procedures for approximately 5 years.

Conditions

Cytomegalovirus Infection

Keywords

Cytomegalovirus, congenital, infants

Outcome Measures

Primary Outcomes (1)

• Change in Best Ear Hearing Assessments at 6 Months.

  Hearing assessment was evaluated by an independent audiologist. At baseline, a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs) hearing assessments were obtained. At 6 months, BSER and /or Visual reinforcement audiometry (VRA) and OAEs were obtained. A single, independent study audiologist who was blinded to treatment assignment assessed the audiology test battery for each subject and assigned the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications were assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. Following this, the study audiologist assigned the "best ear" classification for the subject at that study visit; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification was mild hearing loss.

  Between baseline and 6 months

Secondary Outcomes (23)

• Adverse Events Which Lead to Permanent Discontinuation of Valganciclovir Therapy or Lead to Irreversible Outcome of the Adverse Event.

  baseline through 7 months

• Change in Best Ear Hearing Assessments at 12 Months.

  Between baseline and 12 months

• Change in Best Ear Hearing Assessments at 24 Months.

  Between baseline and 24 months

• Number of Ears With Improvement or Protected Hearing in Hearing Assessments Over Left and Right Ears at 6 Months.(Based on 84 Ears From 43 Placebo Subjects and 82 Ears From 43 Valganciclovir Subjects)

  Between baseline and 6 months

• Number of Ears With Improvement or Protected Hearing in Hearing Assessments Over Left and Right Ears at 12 Months.(Based on 77 Ears From 40 Placebo Subjects and 79 Ears From 41 Valganciclovir Subjects)

  Between baseline and 12 months

Study Arms (2)

Valganciclovir

EXPERIMENTAL

Six months of oral Valganciclovir.

Drug: Valganciclovir

Placebo

PLACEBO COMPARATOR

Six weeks of oral Valganciclovir followed by placebo to complete the six month time period.

Other: Placebo

Interventions

Placebo OTHER

9 grams of powder which contains no Valganciclovir free base. The oral solution formulation comprises the following excipients: mannitol, lactose anhydrous, fumaric acid, sodium benzoate, saccharin sodium, flavor, and purified water.

Placebo

Valganciclovir DRUG

Mono-valyl ester pro-drug of ganciclovir, oral solution, provided as a 12 grams of powder containing 5 grams of Valganciclovir free base. The oral solution formulation comprises the following excipients: Providone K30, fumaric acid, sodium benzoate, sodium saccharin, mannitol, flavor, and purified water.

Valganciclovir

Eligibility Criteria

• Age: Up to 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent from parent(s) or legal guardian(s)
• Confirmation of cytomegalovirus (CMV) from urine or throat swab specimens by culture, shell vial, or polymerase chain reaction (PCR) tests
• Symptomatic congenital CMV disease, as manifest by one or more of the following:
• Thrombocytopenia
• Petechiae
• Hepatomegaly
• Splenomegaly
• Intrauterine growth restriction
• Hepatitis (elevated transaminases and/or bilirubin)
• Central nervous system (CNS) involvement of the CMV disease \[such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal cerebrospinal fluid (CSF) indices for age, chorioretinitis, hearing deficits as detected by formal brainstem evoked response (not a screening auditory brainstem response {ABR}), and/or positive CMV PCR from CSF\]
• Less than or equal to 30 days of age at study enrollment
• Weight at study enrollment greater than or equal to 1800 grams
• Gestational age greater than or equal to 32 weeks at birth

You may not qualify if:

• Imminent demise
• Patients receiving other antiviral agents or immune globulin
• Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)
• Documented renal insufficiency, as noted by a creatinine clearance less than 10 mL/min/1.73m\^2 at time of study enrollment
• Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribivir
• Infants known to be born to women who are human immunodeficiency virus (HIV) positive (but HIV testing is not required for study entry)
• Current receipt of other investigational drugs

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (48)

University of Alabama - Children's of Alabama - Clinical Virology

Birmingham, Alabama, 35233-1711, United States

Location

University of South Alabama - Children's Specialty Clinic

Mobile, Alabama, 36604-3207, United States

Location

Arkansas Children's Hospital - Infectious Diseases

Little Rock, Arkansas, 72202-3500, United States

Location

Los Angeles County - University of Southern California - Medical Center - Pediatrics

Los Angeles, California, 90033-1075, United States

Location

Plaza Towers Obstetrics and Gynecology

Los Angeles, California, 90048-5970, United States

Location

Children's Hospital of Orange County - Infectious Diseases

Orange, California, 92868-3835, United States

Location

Stanford University School of Medicine

Stanford, California, 94305-2200, United States

Location

Children's Hospital Colorado - Infectious Disease

Aurora, Colorado, 80045-7106, United States

Location

Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease

Washington D.C., District of Columbia, 20010-2916, United States

Location

University of Florida - College of Medicine - Jacksonville

Jacksonville, Florida, 32209-6511, United States

Location

University of South Florida - Tampa General Hospital - Pediatrics

Tampa, Florida, 33606-3438, United States

Location

Emory Children's Center - Pediatric Infectious Diseases

Atlanta, Georgia, 30322-1014, United States

Location

University of Louisville School of Medicine - Kosair Childrens Hospital - Infectious Diseases

Louisville, Kentucky, 40202-1821, United States

Location

Tulane University - Tulane Medical Center - Pediatrics

New Orleans, Louisiana, 70112-2600, United States

Location

Louisiana State University Health Shreveport - Pediatrics

Shreveport, Louisiana, 71103-4228, United States

Location

Johns Hopkins Children's Center - Pediatric Infectious Diseases

Baltimore, Maryland, 21287-0011, United States

Location

Children's Hospital Boston - Infectious Diseases

Boston, Massachusetts, 02115-5711, United States

Location

University of Minnesota - Pediatric Infectious Disease

Minneapolis, Minnesota, 55455-0341, United States

Location

University of Mississippi - Children's Infectious Diseases

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital and Clinics - Infectious Diseases

Kansas City, Missouri, 64108-4619, United States

Location

Washington University School of Medicine in St. Louis - Center for Clinical Studies

St Louis, Missouri, 63110-1010, United States

Location

Creighton University Medical Center - Medicine - Infectious Diseases

Omaha, Nebraska, 68131-2137, United States

Location

Childrens Hospital at Saint Peters University Hospital - Allergy, Immunology and Infectious Diseases

New Brunswick, New Jersey, 08901-1766, United States

Location

Robert Wood Johnson Medical School - Pediatrics

New Brunswick, New Jersey, 08901-1935, United States

Location

Women & Children's Hospital of Buffalo - Infectious Diseases

Buffalo, New York, 14222-2006, United States

Location

Cohen Children's Medical Center - Pediatric Infectious Diseases

Manhasset, New York, 11030-3816, United States

Location

University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases

Rochester, New York, 14642-0001, United States

Location

SUNY Upstate Medical University Hospital - Pediatrics

Syracuse, New York, 13210-2342, United States

Location

Carolinas Medical Center - Pediatrics - Infectious Diseases

Charlotte, North Carolina, 28203-5812, United States

Location

MetroHealth Medical Center - Pediatric Infectious Disease

Cleveland, Ohio, 44109-1998, United States

Location

Cleveland Clinic Main Campus - Center for Pediatric Infectious Diseases

Cleveland, Ohio, 44195-0001, United States

Location

Nationwide Children's Hospital - Infectious Diseases

Columbus, Ohio, 43205-2664, United States

Location

Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases

Pittsburgh, Pennsylvania, 15224-1529, United States

Location

Rhode Island Hospital - Pediatrics

Providence, Rhode Island, 02903-4923, United States

Location

Medical University of South Carolina - Pediatrics - Infectious Diseases

Charleston, South Carolina, 29425-8903, United States

Location

Vanderbilt University - Pediatric - Infectious Diseases

Nashville, Tennessee, 37232-0011, United States

Location

Children's Medical Center Dallas - Neonatal ICU

Dallas, Texas, 75235-7701, United States

Location

University of Texas Southwestern Medical Center - Pediatrics

Dallas, Texas, 75390-9063, United States

Location

Cook Children's Infectious Disease Services

Fort Worth, Texas, 76104-2710, United States

Location

University of Utah - Pediatric Pharmacology Program

Salt Lake City, Utah, 84108-1457, United States

Location

Seattle Children's Hospital - Infectious Diseases

Seattle, Washington, 98105-3901, United States

Location

Birmingham Heartlands Hospital

Birmingham, Birmingham, B9 5SS, United Kingdom

Location

Bristol Royal Hospital for Children - UBHT Education Centre

Bristol, Bristol, City of, BS2 8AE, United Kingdom

Location

Alder Hey Childrens Hospital

Liverpool, Liverpool, L12 2AP, United Kingdom

Location

University College London - Royal Free Campus - Virology

London, London, City of, NW3 2PF, United Kingdom

Location

Saint George's Hospital - Pediatric Infectious Diseases

London, London, City of, SW17 0QT, United Kingdom

Location

Newcastle General Hospital

Newcastle upon Tyne, Newcastle upon Tyne, NE4 6BE, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Related Publications (1)

• Kimberlin DW, Jester PM, Sanchez PJ, Ahmed A, Arav-Boger R, Michaels MG, Ashouri N, Englund JA, Estrada B, Jacobs RF, Romero JR, Sood SK, Whitworth MS, Abzug MJ, Caserta MT, Fowler S, Lujan-Zilbermann J, Storch GA, DeBiasi RL, Han JY, Palmer A, Weiner LB, Bocchini JA, Dennehy PH, Finn A, Griffiths PD, Luck S, Gutierrez K, Halasa N, Homans J, Shane AL, Sharland M, Simonsen K, Vanchiere JA, Woods CR, Sabo DL, Aban I, Kuo H, James SH, Prichard MN, Griffin J, Giles D, Acosta EP, Whitley RJ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015 Mar 5;372(10):933-43. doi: 10.1056/NEJMoa1404599.

  PMID: 25738669 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: David Kimberlin, MD
• Organization: University of Alabama in Birmingham

dkimberlin@peds.uab.edu

205-934-2424

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2007
• First Posted: April 27, 2007
• Study Start: June 1, 2008
• Primary Completion: December 1, 2011
• Study Completion: June 1, 2013
• Last Updated: August 26, 2015
• Results First Posted: November 13, 2013

Record last verified: 2015-07

Locations

US (41); GB (7)