Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01649869
• Collaborator: (none)
• Enrollment: 54
• Locations: 18
• Arms: 2
• Actual Duration (Months): 58
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is an international, multi-center, double-blind, placebo-controlled evaluation valganciclovir treatment for up to 54 children (up to 4 years of age) with virologically-confirmed congenital CMV infection and hearing loss. Subject participation will be over a six-month period and study subjects will be stratified according to age. The primary objective is to assess whether a six-week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infection	Other: Placebo; Drug: Valganciclovir	Phase 2

Detailed Description

Congenital cytomegalovirus (CMV) infection is the most frequent known viral cause of mental retardation, and is the leading non-genetic cause of sensorineural hearing loss in many countries including the United States. This is a Phase II international, multi-center, double-blind, placebo-controlled evaluation of 6 weeks of oral valganciclovir treatment or 6 weeks of placebo for fifty-four male and female infants/toddlers 1 month through 3 years of age (up to 4 years of age) with virologically-confirmed congenital CMV infection and hearing loss. Patient who are between 1 month and 4 years of age and who have SNHL (Sensorineural Hearing Loss) and are eligible for enrollment. The expected study duration is 3.5 years from enrollment of first study subject. The primary objective is to assess whether a six week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss. The secondary objective is to define the following responses as a function of systemic exposure to ganciclovir (active metabolite of valganciclovir): CMV viral load in blood; CMV viral load in urine; and CMV viral load in saliva. Also, to define the safety and tolerability of valganciclovir in enrolled subjects. The tertiary objective is to define the pharmacokinetics of ganciclovir (metabolite) following administration of valganciclovir (prodrug) in enrolled subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized and Controlled Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children With Congenital Cytomegalovirus Infection and Hearing Loss
• Actual Study Start Date: Feb 24, 2015
• Actual Primary Completion Date: Dec 24, 2019
• Actual Study Completion Date: Dec 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active 27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks	Drug: Valganciclovir; Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Placebo Comparator: Placebo 27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks	Other: Placebo; Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Ears That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss. Not both ears are evaluable for all subjects. In some subjects, only one ear is evaluable.

Secondary Outcome Measures

1. Number of Best Ear That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing [ex. Improved+ no Change (Normal to Normal) Versus Other]. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss. For this outcome, we combine the improved hearing and no change for the special case only of normal to normal. Other category include worsened and no change from (1) mild to mild hearing loss, (2) moderate to moderate hearing loss, or (3) severe to severe hearing loss.

2. Change in Best Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.

3. Change in Best Ear Hearing Assessments [Worse + no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.

4. Change in Best Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.

5. Change in Total Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.

6. Change in Total Ear Hearing Assessments [Worse+ no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.

7. Change in Total Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6. [Day 1 through Day 180]

   A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.

8. Association of Change in Viral Load (Blood) With Change in Total Ear Hearing at 6 Months [At 6 months]

   Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.

9. Association of Change in Viral Load (Saliva) With Change in Total Ear Hearing at 6 Months [At 6 months]

   Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units or log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.

10. Association of Change in Viral Load (Urine) With Change in Total Ear Hearing at 6 Months [At 6 months]

    Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.

11. Association of Change in Viral Load (Blood) With Change in Best Ear Hearing at 6 Months [At 6 months]

    Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.

12. Association of Change in Viral Load (Saliva) With Change in Best Ear Hearing at 6 Months [At 6 months]

    Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.

13. Association of Change in Viral Load (Urine) With Change in Best Ear Hearing at 6 Months [At 6 months]

    Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.

14. Detection of Viruria (Urine) by PCR Six Weeks After Trial Entry [At 6 weeks (Day 42)]

    Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.

15. Detection of Viruria (Urine) by PCR Six Month After Trial Entry [At 6 months]

    Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.

16. Detection of Viremia (Blood) by PCR Six Weeks After Trial Entry [At 6 weeks (Day 42)]

    Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.

17. Detection of Viremia (Blood) by PCR Six Month After Trial Entry [At 6 months]

    Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.

18. Detection of CMV in Saliva by PCR Six Weeks After Trial Entry [At 6 weeks (Day 42)]

    Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.

19. Detection of CMV in Saliva PCR Six Month After Trial Entry [At 6 months]

    Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.

20. The Quantitative Log Change in Viremia From Baseline to Month 6. [Baseline to month 6]

    The quantitative change (Month 6 minus baseline) in viremia (blood) Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units).

21. The Quantitative Log Reduction in Viruria Detected After 6 Weeks of Therapy [Baseline thru months 6]

    The quantitative log reduction in viruria (urine) detected after 6 weeks of therapy. Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units)

22. The Quantitative Log Reduction in CMV in Saliva Detected After 6 Weeks of Therapy [Baseline thru months 6]

    The quantitative log reduction in CMV in saliva (urine) detected after 6 weeks of therapy. Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units)

23. Number of Adverse Events in the Active Group That Resulted in Discontinuation of Valganciclovir [Day 1 thru day 70]

    AE resulting in discontinuation of valganciclovir (active group only). This outcome summarizes the number of adverse events (AEs) that resulted in the discontinuation of valganciclovir in the active group only.

24. Adverse Event (AE) Resulting in Unresolved Outcome [Day 1 thru day 70]

    Adverse event resulting in unresolved outcome. This outcome summarizes the number of adverse events (AEs) that resulted in unresolved outcome of that AE.

25. Adverse Event (AE) Resulting in Unanticipated Medically Attended Visit [Day 1 thru day 70]

    Adverse event resulting in unanticipated medically attended visit. This outcome summarizes the number of adverse events (AEs) that resulted in the unanticipated medically attended visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 4 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Signed informed consent from parent(s) or legal guardian(s)

2. Sensorineural hearing loss (>/= 21dB in one or both ears, documented within 12 weeks prior to study entry)

3. Children from 1 month through 3 years of age (up to the 4th birthday)

Exclusion Criteria:

1. Imminent demise

2. Profound sensorineural hearing loss (> 90dB) in both ears

3. Patients receiving other antiviral agents or immune globulin

4. Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)

5. Documented renal insufficiency, as noted by a creatinine clearance < 10 mL/min/1.73m2 at time of study enrollment

6. Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribavir

7. Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).

8. Current receipt of other investigational drugs

9. Previous receipt of ganciclovir or valganciclovir

10. Known hypersensitivity to ganciclovir, valganciclovir, or components of the product

11. Inability to attend follow-up hearing and clinical assessments

12. Infants with Auditory neuropathy/dyssynchrony.

13. Children with another known etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis).

Exclusion of each of these conditions is not required for trial enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Children's of Alabama - Clinical Virology	Birmingham	Alabama	United States	35233-1711
2	Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease	Washington	District of Columbia	United States	20010-2916
3	Washington University School of Medicine in St. Louis - Center for Clinical Studies	Saint Louis	Missouri	United States	63110-1010
4	Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease	Manhasset	New York	United States	11030-3816
5	University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases	Rochester	New York	United States	14642-0001
6	Carolinas Medical Center - Pediatrics - Infectious Diseases	Charlotte	North Carolina	United States	28203-5812
7	Nationwide Children's Hospital - Neonatology - Center for Perinatal Research	Columbus	Ohio	United States	43205-2664
8	Rhode Island Hospital - Pediatrics	Providence	Rhode Island	United States	02903-4923
9	Texas Medical Center - Texas Children's Hospital	Houston	Texas	United States	77030
10	Bristol Royal Hospital for Children - Paediatric Immunology	Bristol	Bristol, City Of	United Kingdom	BS2 8BJ
11	Saint George's Hospital - Pediatric Infectious Diseases	London	London, City Of	United Kingdom	SW17 0QT
12	Great Ormond Street Hospital - Infectious Diseases	London	London, City Of	United Kingdom	WC1N 3JH
13	Birmingham Heartlands Hospital	Birmingham		United Kingdom	B9 5SS
14	Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services	Crumpsall		United Kingdom	M8 5RB
15	John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology	Headington, Oxford		United Kingdom	OX3 9DU
16	The Great North Children's Hospital - Paediatric Immunology	Newcastle Upon Tyne		United Kingdom	NE14LP
17	Sheffield Children's Hospital - Immunology	Sheffield		United Kingdom	S10 2TH
18	Southampton Children's Hospital - Allergy, Immunology and Infection	Southampton, Hampshire		United Kingdom	SO16 6YD

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Apr 28, 2016
• Statistical Analysis Plan - Aug 14, 2020

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01649869
• Other Study ID Numbers: 11-0069; HHSN272201100035C
• First Posted: Jul 25, 2012
• Last Update Posted: Jun 2, 2021
• Last Verified: Mar 22, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): CMV; Cytomegalovirus; Hearing Loss; Infants; Valganciclovir
• Additional relevant MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections; Hearing Loss; Deafness; Valganciclovir

Study Results

Participant Flow

Recruitment Details	For this study, subjects were enrolled once they signed the informed consent form (ICF). It was not until after hearing loss was confirmed by audiology testing and confirmation of congenital CMV by dried blood spot that a subject was randomized and started on study drug. This reduced protocol enrollment from 54 to 35.

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Period Title: Overall Study
STARTED	18	17
COMPLETED	16	16
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Placebo	Active	Total
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.	Total of all reporting groups
Overall Participants	18	17	35
Age (MONTHS) [Median (Standard Deviation) ]
Median (Standard Deviation) [MONTHS]	19.5 (13.1)	17.8 (15.8)	18.7 (14.3)
Sex: Female, Male (Count of Participants)
Female	8 44.4%	6 35.3%	14 40%
Male	10 55.6%	11 64.7%	21 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	17 94.4%	15 88.2%	32 91.4%
Unknown or Not Reported	1 5.6%	2 11.8%	3 8.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 5.6%	2 11.8%	3 8.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 11.1%	2 11.8%	4 11.4%
White	15 83.3%	12 70.6%	27 77.1%
More than one race	0 0%	1 5.9%	1 2.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	7 38.9%	4 23.5%	11 31.4%
United Kingdom	11 61.1%	13 76.5%	24 68.6%

Outcome Measures

1. Primary Outcome

Title	Number of Ears That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss. Not both ears are evaluable for all subjects. In some subjects, only one ear is evaluable.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	16	15
Measure Ears	28	26
Improve + no change	27	20
Worsened	1	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0859
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome based on generalized estimating equations.

2. Secondary Outcome

Title	Number of Best Ear That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing [ex. Improved+ no Change (Normal to Normal) Versus Other].
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss. For this outcome, we combine the improved hearing and no change for the special case only of normal to normal. Other category include worsened and no change from (1) mild to mild hearing loss, (2) moderate to moderate hearing loss, or (3) severe to severe hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	15	12
Improved + normal to normal	9 50%	6 35.3%
No change abnormal or worsened	6 33.3%	6 35.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7068
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change in Best Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	15	12
Improved	0 0%	0 0%
No change or worsened	15 83.3%	12 70.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Change in Best Ear Hearing Assessments [Worse + no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	15	12
No change abnormal to abnormal + worsened	6 33.3%	6 35.3%
Improved + normal to normal	9 50%	6 35.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7068
	Comments
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Change in Best Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	15	12
Worsened	0 0%	3 17.6%
Other	15 83.3%	9 52.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0752
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Change in Total Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	16	15
Measure Ears	28	26
Improved	0	0
Other	28	26

7. Secondary Outcome

Title	Change in Total Ear Hearing Assessments [Worse+ no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	16	15
Measure Ears	28	26
worse + no change (abnormal to abnormal)	19	20
Other	9	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4823
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome using generalized estimating equations.

8. Secondary Outcome

Title	Change in Total Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
Description	A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; 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 will be mild hearing loss.
Time Frame	Day 1 through Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	16	15
Measure Ears	28	26
Worsened	1	6
Other	27	20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0859
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome using generalized estimating equations.

9. Secondary Outcome

Title	Association of Change in Viral Load (Blood) With Change in Total Ear Hearing at 6 Months
Description	Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Analysis was stratified by hearing outcome--total analyzed is the sum of the number analyzed for 2 rows below

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	31
Measure Ears	54
Improved + normal to normal	1.396 (0.542)
No change abnormal + worsened	1.326 (0.566)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Association of binary outcome and continuous outcome
Statistical Test of Hypothesis	p-Value	0.8212
	Comments
	Method	Generalized linear model
	Comments	For binary outcome using generalized estimating equations

10. Secondary Outcome

Title	Association of Change in Viral Load (Saliva) With Change in Total Ear Hearing at 6 Months
Description	Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units or log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Analysis stratified by hearing outcome--total analyzed is the sum of the number analyzed for 2 rows belos

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	31
Measure Ears	54
Improved + normal to normal	2.447 (1.715)
No change abnormal + worsened	2.290 (1.349)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Association of binary outcome and continuous outcome and continuous outcome
Statistical Test of Hypothesis	p-Value	0.8356
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome using generalized estimating equations.

11. Secondary Outcome

Title	Association of Change in Viral Load (Urine) With Change in Total Ear Hearing at 6 Months
Description	Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Analysis stratified by hearing outcome--total analyzed is the sum of the number analyzed for 2 rows below

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	29
Measure Ears	50
Improved + normal to normal	3.562 (1.139)
No change abnormal + worsened	3.583 (1.370)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Association of binary outcome and continuous outcome
Statistical Test of Hypothesis	p-Value	0.7961
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome using generalized estimating equations

12. Secondary Outcome

Title	Association of Change in Viral Load (Blood) With Change in Best Ear Hearing at 6 Months
Description	Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Analysis stratified by hearing outcome--total analyzed is the sum of the number analyzed for 2 rows below

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	27
Improved + normal to normal	1.396 (0.542)
No change abnormal + worsened	1.359 (0.668)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Association of binary outcome and continuous outcome
Statistical Test of Hypothesis	p-Value	0.8675
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome

13. Secondary Outcome

Title	Association of Change in Viral Load (Saliva) With Change in Best Ear Hearing at 6 Months
Description	Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Analysis stratified by hearing outcome--total analyzed is the sum of the number analyzed for 2 rows below

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	27
Improved + normal to normal	2.447 (1.715)
No change abnormal + worsened	2.423 (1.484)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Association of binary outcome and continuous outcome
Statistical Test of Hypothesis	p-Value	0.9682
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome

14. Secondary Outcome

Title	Association of Change in Viral Load (Urine) With Change in Best Ear Hearing at 6 Months
Description	Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml*days divided by days in study which equals log 10 copies/ml.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Analysis stratified by hearing outcome--total analyzed is the sum of the number of analyzed for 2 rows below

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	25
Improved + normal to normal	3.562 (1.139)
No change abnormal + worsened	3.831 (1.570)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Association of binary outcome and continuous outcome
Statistical Test of Hypothesis	p-Value	0.6063
	Comments
	Method	Generalized linear model
	Comments	Generalized linear model for binary outcome

15. Secondary Outcome

Title	Detection of Viruria (Urine) by PCR Six Weeks After Trial Entry
Description	Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame	At 6 weeks (Day 42)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	12	12
Positive	11 61.1%	1 5.9%
Negative	1 5.6%	11 64.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Fisher Exact
	Comments

16. Secondary Outcome

Title	Detection of Viruria (Urine) by PCR Six Month After Trial Entry
Description	Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	11	14
Positive	10 55.6%	11 64.7%
Negative	1 5.6%	3 17.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6043
	Comments
	Method	Fisher Exact
	Comments

17. Secondary Outcome

Title	Detection of Viremia (Blood) by PCR Six Weeks After Trial Entry
Description	Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame	At 6 weeks (Day 42)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	15	14
Positive	4 22.2%	2 11.8%
Negative	11 61.1%	12 70.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6513
	Comments
	Method	Fisher Exact
	Comments

18. Secondary Outcome

Title	Detection of Viremia (Blood) by PCR Six Month After Trial Entry
Description	Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	15	15
Positive	4 22.2%	3 17.6%
Negative	11 61.1%	12 70.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

19. Secondary Outcome

Title	Detection of CMV in Saliva by PCR Six Weeks After Trial Entry
Description	Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame	At 6 weeks (Day 42)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	16	16
Positive	9 50%	3 17.6%
Negative	7 38.9%	13 76.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0659
	Comments
	Method	Fisher Exact
	Comments

20. Secondary Outcome

Title	Detection of CMV in Saliva PCR Six Month After Trial Entry
Description	Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	16	16
Positive	8 44.4%	7 41.2%
Negative	8 44.4%	9 52.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Active
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Fisher Exact
	Comments

21. Secondary Outcome

Title	The Quantitative Log Change in Viremia From Baseline to Month 6.
Description	The quantitative change (Month 6 minus baseline) in viremia (blood) Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units).
Time Frame	Baseline to month 6

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed=34: 17 active and 17 placebo

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	34
Active	0.4908
Placebo	-0.1528

22. Secondary Outcome

Title	The Quantitative Log Reduction in Viruria Detected After 6 Weeks of Therapy
Description	The quantitative log reduction in viruria (urine) detected after 6 weeks of therapy. Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units)
Time Frame	Baseline thru months 6

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed=28: 15 active and 13 placebo

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	28
Active	1.2152
Placebo	0.8390

23. Secondary Outcome

Title	The Quantitative Log Reduction in CMV in Saliva Detected After 6 Weeks of Therapy
Description	The quantitative log reduction in CMV in saliva (urine) detected after 6 weeks of therapy. Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units)
Time Frame	Baseline thru months 6

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed=34

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Measure Participants	34
Active	1.3202
Placebo	0.0057

24. Secondary Outcome

Title	Number of Adverse Events in the Active Group That Resulted in Discontinuation of Valganciclovir
Description	AE resulting in discontinuation of valganciclovir (active group only). This outcome summarizes the number of adverse events (AEs) that resulted in the discontinuation of valganciclovir in the active group only.
Time Frame	Day 1 thru day 70

Outcome Measure Data

Analysis Population Description

No participants in the active group were discontinued due to adverse event.

Arm/Group Title	Randomized Group
Arm/Group Description	Randomized children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir orally twice a day for 6 weeks
Measure Participants	17
No	17 94.4%
Yes	0 0%

25. Secondary Outcome

Title	Adverse Event (AE) Resulting in Unresolved Outcome
Description	Adverse event resulting in unresolved outcome. This outcome summarizes the number of adverse events (AEs) that resulted in unresolved outcome of that AE.
Time Frame	Day 1 thru day 70

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed=18

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	18	17
No	18 100%	17 100%
Yes	0 0%	0 0%

26. Secondary Outcome

Title	Adverse Event (AE) Resulting in Unanticipated Medically Attended Visit
Description	Adverse event resulting in unanticipated medically attended visit. This outcome summarizes the number of adverse events (AEs) that resulted in the unanticipated medically attended visit.
Time Frame	Day 1 thru day 70

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed=18

Arm/Group Title	Placebo	Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Measure Participants	18	17
No	15 83.3%	17 100%
Yes	3 16.7%	0 0%

Adverse Events

Time Frame	All AEs and SAEs from Study Day 1 through four weeks following the last dose of study drug. All AEs and SAEs will be followed until resolution, even if this extends beyond the study reporting period. Resolution of an AE is defined as the return to pretreatment status or stabilization of the condition with the expectation that it will remain chronic.
Adverse Event Reporting Description	Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product whether or not considered drug related. The occurrence of an AE may come to the attention of study personnel during study visits and interviews of a study recipient presenting for medical care, or upon review by a study monitor.
Arm/Group Title	Placebo		Active
Arm/Group Description	27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks Placebo: Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks		27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks Valganciclovir: Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
All Cause Mortality
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/17 (0%)
Serious Adverse Events
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory Distress	0/18 (0%)	0	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/35 (51.4%)		17/35 (48.6%)
Blood and lymphatic system disorders
Decrease in hemoglobin	1/18 (5.6%)	1	0/17 (0%)	0
Neutropenia	2/18 (11.1%)	4	1/17 (5.9%)	1
Monocytopenia	0/18 (0%)	0	1/17 (5.9%)	1
Ear and labyrinth disorders
Bilateral ear infection	1/18 (5.6%)	1	0/17 (0%)	0
Otitis Media	1/18 (5.6%)	1	1/17 (5.9%)	1
Ear Infection	0/18 (0%)	0	1/17 (5.9%)	1
Gastrointestinal disorders
Constipation	2/18 (11.1%)	3	1/17 (5.9%)	1
Diarrhoea	0/18 (0%)	0	1/17 (5.9%)	1
Emesis	0/18 (0%)	0	1/17 (5.9%)	1
Gastroenteritis	0/18 (0%)	0	1/17 (5.9%)	1
Loose stools	1/18 (5.6%)	2	0/17 (0%)	0
Reduced Appetite	0/18 (0%)	0	1/17 (5.9%)	1
Reflux	0/18 (0%)	0	1/17 (5.9%)	1
Teething	2/18 (11.1%)	2	2/17 (11.8%)	2
Viral Gastroenteritis	0/18 (0%)	0	1/17 (5.9%)	1
Vomiting	2/18 (11.1%)	5	4/17 (23.5%)	4
Weight Loss	0/18 (0%)	0	1/17 (5.9%)	1
General disorders
Fall on chin	1/18 (5.6%)	1	0/17 (0%)	0
Fever	3/18 (16.7%)	3	1/17 (5.9%)	1
Hyperkalemia	0/18 (0%)	0	1/17 (5.9%)	1
Long Sighted	0/18 (0%)	0	1/17 (5.9%)	1
Nose Bleed	1/18 (5.6%)	1	0/17 (0%)	0
Pyrexia	0/18 (0%)	0	1/17 (5.9%)	1
Raised Temperature	1/18 (5.6%)	1	0/17 (0%)	0
Infections and infestations
Chicken Pox	1/18 (5.6%)	1	0/17 (0%)	0
Hand, Foot and Mouth Disease	1/18 (5.6%)	1	1/17 (5.9%)	1
Infection at Surgical Incision Site	0/18 (0%)	0	1/17 (5.9%)	1
Rhinitis	1/18 (5.6%)	1	0/17 (0%)	0
Tonsillitis	1/18 (5.6%)	1	1/17 (5.9%)	1
Viral Illness	2/18 (11.1%)	3	1/17 (5.9%)	1
Injury, poisoning and procedural complications
Head, Eye and Right Arm Injury--Suspected trauma to lacrimal sac.	0/18 (0%)	0	1/17 (5.9%)	1
Minor Injury--Bruise Right Eye and Cheek and Left Forehead	0/18 (0%)	0	1/17 (5.9%)	1
Musculoskeletal and connective tissue disorders
Buckle Fracture of Right Tibia and Fibula	0/18 (0%)	0	1/17 (5.9%)	1
Osteopenia	0/18 (0%)	0	1/17 (5.9%)	1
Psychiatric disorders
Agitation	1/18 (5.6%)	1	0/17 (0%)	0
Crying since first dose	1/18 (5.6%)	1	0/17 (0%)	0
Fussiness	1/18 (5.6%)	1	0/17 (0%)	0
Hallucination-Nightmare	0/18 (0%)	0	1/17 (5.9%)	1
Intermittent Hyperactivity	1/18 (5.6%)	1	0/17 (0%)	0
Lethargic and Sleeping more than usual	0/18 (0%)	0	1/17 (5.9%)	1
Screaming--Unsettled	0/18 (0%)	0	1/17 (5.9%)	1
Renal and urinary disorders
Blood in Urine	0/18 (0%)	0	1/17 (5.9%)	1
Protein in Urine	0/18 (0%)	0	1/17 (5.9%)	1
Urinary Incontinence	1/18 (5.6%)	1	0/17 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/18 (0%)	0	1/17 (5.9%)	1
Blocked Nose	0/18 (0%)	0	1/17 (5.9%)	1
Bronchiolitis	0/18 (0%)	0	2/17 (11.8%)	2
Coryzal Symptoms	1/18 (5.6%)	2	2/17 (11.8%)	2
Cough	2/18 (11.1%)	5	1/17 (5.9%)	1
Cough and Runny Nose	0/18 (0%)	0	1/17 (5.9%)	1
Cough and Cold	1/18 (5.6%)	1	0/17 (0%)	0
Exacerbation	0/18 (0%)	0	1/17 (5.9%)	1
Upper Respiratory Tract Infection	2/18 (11.1%)	2	1/17 (5.9%)	1
Rhinos Virus Infection	0/18 (0%)	0	1/17 (5.9%)	1
Runny Nose	0/18 (0%)	0	1/17 (5.9%)	1
Skin and subcutaneous tissue disorders
Fine Erythematous, raised rash on Chest and Abdomen	0/18 (0%)	0	1/17 (5.9%)	1
Glass in Foot	0/18 (0%)	0	1/17 (5.9%)	1
Impetigo	0/18 (0%)	0	1/17 (5.9%)	1
Rash	0/18 (0%)	0	2/17 (11.8%)	4
White Discolouration of Lips and Throat	1/18 (5.6%)	1	0/17 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.