CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01552369
• Collaborator: (none)
• Enrollment: 205
• Locations: 6
• Arms: 2
• Actual Duration (Months): 67.7
• Patients Per Site: 34.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is a trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in R-D+ liver transplant patients. Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir, 900 mg orally once daily or preemptive therapy (weekly monitoring for CMV viremia by plasma PCR) for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia and continued until plasma PCR is negative on two consecutive weekly PCR tests). A minimum of 176 subjects will be enrolled in the study. The study duration is 7 years. The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infection	Drug: Valganciclovir	Phase 4

Detailed Description

This is a prospective, randomized, multicenter trial of preemptive therapy vs. prophylaxis for prevention of Cytomegalovirus (CMV) disease in seronegative recipient- seropositive donor (R-D+) liver transplant patients.Subjects will be randomized within 10 days of transplant to receive in an open label design, either antiviral prophylaxis with valganciclovir 900 mg orally once daily or preemptive therapy for 100 days post-randomization with initiation of oral valganciclovir 900mg orally twice daily at onset of CMV viremia (monitored weekly) and continued until plasma PCR is negative on two consecutive weekly PCR tests. Study participants will be followed during the intervention period (100 days post randomization) and until 12 months post-transplant for CMV disease, toxicity, and clinical outcomes (opportunistic infections, rejection, graft loss and mortality). Drug safety labs will be assessed and recorded for the entire treatment period in both the prophylaxis and preemptive group. Re-transplantation and all-cause mortality will also be assessed at study closure and no longer than 5 years after enrollment. Additionally, the impact of the two CMV prevention strategies on CMV-specific cellular and humoral immune responses will be evaluated at 100 days after randomization, and 6 and 12 months post-transplant. A minimum of 176 subjects will be enrolled in the study. Allowing for over-enrollment to replace dropouts, up to 205 subjects may be enrolled to achieve the target enrollment of 176. Subjects will be randomized into one of the two groups in 1:1 ratio. The study duration is 7 years. The primary objective of this study is to compare prophylaxis versus preemptive therapy using valganciclovir for the prevention of CMV disease in R-/D+ liver transplant recipients. The secondary objectives are:1) to assess the two preventive strategies for clinical outcomes (major bacterial, fungal and non-CMV viral infections, rejection, graft loss and mortality) at one year post transplantation; 2) to assess the two preventive strategies for hematologic toxicity (assessment of neutropenia and receipt of hematopoietic growth factor during study days 1-107).

Study Design

• Study Type: Interventional
• Actual Enrollment: 205 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prophylaxis Versus Preemptive Therapy for the Prevention of CMV in High-Risk R-D+ Liver Transplant Recipients
• Actual Study Start Date: Oct 29, 2012
• Actual Primary Completion Date: Jun 22, 2018
• Actual Study Completion Date: Jun 22, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Preemptive Therapy 900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction. n=88	Drug: Valganciclovir; Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis. Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.
Active Comparator: Prophylaxis 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=88	Drug: Valganciclovir; Valganciclovir, 900 mg given orally once daily to all Prophylaxis group subjects for 100 days post transplantation as prophylaxis. Valganciclovir, 900 mg given orally twice daily to Preemptive Therapy group subjects as a PET only after a positive CMV PCR test and stopped after PCR is negative for 2 consecutive weeks.

Outcome Measures

Primary Outcome Measures

1. Incidence of Cytomegalovirus (CMV) Disease. [365 days post-transplant]

   CMV disease as verified by an independent end point committee

Secondary Outcome Measures

1. All-cause Mortality [Up to 365 days post-transplant]

   Survival probability at 1 year

2. Incidence of Allograft Rejection [Up to 365 days post-transplant]

   Number of subjects with allograft rejection

3. Graft Loss [Up to 365 days post-transplant]

   Incidence of graft loss (re-transplantation)

4. Late-onset CMV Disease [Up to 365 days post-transplant]

   Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee

5. Bacterial Infections [Up to 365 days post-transplant]

   Incidence of bacterial opportunistic infections

6. Major Fungal Infections [Up to 365 days post-transplant]

   Opportunistic fungal infections

7. Major Non-CMV Viral Infections [Up to 365 days post-transplant]

   Incidence of non-CMV viral infections

8. Neutropenia [Day 1 through Day 107]

   Incidence of neutropenia less than 1000/µL while on valganciclovir treatment

9. Neutropenia Less Than 500 [prior to day 107]

   ANC less than 500 while on valganciclovir

10. Hematopoietic Growth Factors [Day 1 through Day 107]

    Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Be > / = 18 years of age.

2. Have negative Cytomegalovirus (CMV) serology (confirmed within 6 months of transplant) and receive a liver from a donor with positive CMV serology (R-/D+).

3. Have received their first orthotopic liver transplant (the transplanted liver may be deceased donor or live donor graft) within 10 days prior.

4. Have absolute neutrophil count > 1000/µL at randomization.

5. • If female, and not postmenopausal or surgically sterile, must have negative pregnancy test (serum or urine) within 48 hours prior to randomization and must also agree to use medically approved method of contraception. Acceptable methods include: barrier method, intrauterine device (hormonal or non-hormonal), oral hormonal contraceptives, abstinence for 100 days after randomization and 3 months after valganciclovir cessation.

-- If male, and has not had a vasectomy, he must agree to practice barrier method of contraception for 100 days after randomization and 3 months after valganciclovir cessation.

1. Subject or legally authorized representative has provided written informed consent.

Exclusion Criteria:

1. Currently enrolled in any interventional trial of an investigational therapeutic agent unless co-enrollment has been approved by study Principal Investigators (PIs) and the DMID prior to enrollment.

2. Have hypersensitivity to acyclovir, ganciclovir or valganciclovir.

3. Be breast-feeding mother.

4. Have known Human immunodeficiency virus (HIV) infection (based on testing performed during the transplant evaluation process).

5. Be undergoing multi organ transplant or have undergone prior organ transplant.

6. Have expected life expectancy of less than 72 hours.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ronald Reagan University of California Los Angeles Medical Center	Los Angeles	California	United States	90095-8358
2	Emory Clinic - Transplant Center	Atlanta	Georgia	United States	30322-1013
3	Mayo Clinic, Rochester - Infectious Diseases	Rochester	Minnesota	United States	55905-0001
4	Mount Sinai School of Medicine - Medicine - Infectious Diseases	New York	New York	United States	10029-6504
5	University of Pittsburgh - Medicine - Infectious Diseases	Pittsburgh	Pennsylvania	United States	15213-3403
6	University of Washington - Medicine	Seattle	Washington	United States	98195-7110

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 21, 2016

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01552369
• Other Study ID Numbers: 11-0073
• First Posted: Mar 13, 2012
• Last Update Posted: Aug 26, 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 infections; ganciclovir; liver transplant; preemptive therapy; prophylaxis; valganciclovir
• Additional relevant MeSH terms: Cytomegalovirus Infections; Valganciclovir

Study Results

Participant Flow

Pre-assignment Detail	538 liver transplant candidates or recipients were screened. 333 were not eligible. 229 did not meet inclusion criteria. 29 met at least 1 exclusion criteria. 75 unable to give, or refused consent. No study procedures were conducted on these 333 subjects.

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction. n=100	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=105
Period Title: Overall Study
STARTED	100	105
One Year	100	105
Final Follow up	92	96
COMPLETED	92	96
NOT COMPLETED	8	9

Baseline Characteristics

Arm/Group Title	Preemptive Therapy	Prophylaxis	Total
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction. n=100	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=105	Total of all reporting groups
Overall Participants	100	105	205
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	57	58	58
Sex: Female, Male (Count of Participants)
Female	35 35%	27 25.7%	62 30.2%
Male	65 65%	78 74.3%	143 69.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 8%	11 10.5%	19 9.3%
Not Hispanic or Latino	92 92%	94 89.5%	186 90.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2%	2 1.9%	4 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 6%	3 2.9%	9 4.4%
White	90 90%	99 94.3%	189 92.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 2%	1 1%	3 1.5%
Region of Enrollment (participants) [Number]
United States	100 100%	105 100%	205 100%
Baseline absolute neutrophil count(ANC) (Count per 1000 cells/µL) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [Count per 1000 cells/µL]	6888	7409	7160

Outcome Measures

1. Primary Outcome

Title	Incidence of Cytomegalovirus (CMV) Disease.
Description	CMV disease as verified by an independent end point committee
Time Frame	365 days post-transplant

Outcome Measure Data

Analysis Population Description

All randomized subjects

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Number [participants]	9 9%	20 19%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0396
	Comments
	Method	Mantel Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	Competing risk regression
	Comments	Death was considered a competing risk.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.22
	Confidence Interval	(2-Sided) 95%; 1.01 to 7.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The risk of CMV disease is 2.2x higher in the prophylaxis group when compared to the preemptive group

2. Secondary Outcome

Title	All-cause Mortality
Description	Survival probability at 1 year
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) population

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction. n=100	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=105
Measure Participants	100	105
Number (95% Confidence Interval) [survivor probabillity]	.880	.933

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments	log-rank test for equality of survivor functions
Statistical Test of Hypothesis	p-Value	0.19
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Incidence of Allograft Rejection
Description	Number of subjects with allograft rejection
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	28 28%	26 24.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.45 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds of rejection in prophylaxis group compared to preemptive group

4. Secondary Outcome

Title	Graft Loss
Description	Incidence of graft loss (re-transplantation)
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	2 2%	2 1.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.13 to 6.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	The odds of graft loss in prophylaxis group compared to preemptive group

5. Secondary Outcome

Title	Late-onset CMV Disease
Description	Incidence of late-onset CMV disease (occurring after 100 days post-randomization) as adjudicated by end point committee
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	6 6%	18 17.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.24
	Confidence Interval	(2-Sided) 95%; 1.21 to 8.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds of late disease in prophylaxis group compared to preemptive

6. Secondary Outcome

Title	Bacterial Infections
Description	Incidence of bacterial opportunistic infections
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	22 22%	26 24.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.61 to 2.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds of bacterial infection in prophylaxis subjects compared to preemptive

7. Secondary Outcome

Title	Major Fungal Infections
Description	Opportunistic fungal infections
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	4 4%	9 8.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.25
	Confidence Interval	(2-Sided) 95%; 0.66 to 7.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds of fungal disease in prophylaxis group compared to preemptive

8. Secondary Outcome

Title	Major Non-CMV Viral Infections
Description	Incidence of non-CMV viral infections
Time Frame	Up to 365 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	2 2%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Neutropenia
Description	Incidence of neutropenia less than 1000/µL while on valganciclovir treatment
Time Frame	Day 1 through Day 107

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	36 36%	35 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Chi-squared
	Comments

10. Secondary Outcome

Title	Neutropenia Less Than 500
Description	ANC less than 500 while on valganciclovir
Time Frame	prior to day 107

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	12 12%	10 9.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Chi-squared
	Comments

11. Secondary Outcome

Title	Hematopoietic Growth Factors
Description	Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.
Time Frame	Day 1 through Day 107

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Preemptive Therapy	Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.	900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Measure Participants	100	105
Count of Participants [Participants]	5 5%	7 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Preemptive Therapy, Prophylaxis
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Liver transplant recipients represent a population in whom a high rate of medical events are commonly seen during the post-transplant course. For this study, adverse events were: Any clinically important untoward medical occurrence in a subject receiving study drug that is different from what is expected in the clinical course of a patient with a liver transplant. Any clinically important, untoward medical occurrence thought to be related to the study drug, regardless of 'expectedness'.
Arm/Group Title	Preemptive Therapy		Prophylaxis
Arm/Group Description	900 mg of Valganciclovir given orally twice daily to Preemptive Therapy subjects upon detection of CMV viremia until plasma PCR is negative on two consecutive weekly PCR test. All dosages adjusted for renal dysfunction.		900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
All Cause Mortality
	Preemptive Therapy		Prophylaxis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/100 (12%)		7/105 (6.7%)
Serious Adverse Events
	Preemptive Therapy		Prophylaxis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/100 (2%)		0/105 (0%)
Cardiac disorders
Pericardial effusion	1/100 (1%)	1	0/105 (0%)	0
Renal and urinary disorders
Kidney stone	1/100 (1%)	1	0/105 (0%)	0
Other (Not Including Serious) Adverse Events
	Preemptive Therapy		Prophylaxis
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/100 (1%)		1/105 (1%)
Blood and lymphatic system disorders
leukopenia	1/100 (1%)	1	1/105 (1%)	1

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.