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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01552369
Recruitment Status : Completed
First Posted : March 13, 2012
Results First Posted : July 2, 2019
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cytomegalovirus Infection
Intervention Drug: Valganciclovir
Enrollment 205
Recruitment Details  
Pre-assignment Details 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
Hide 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 [1] 100 105
Final Follow up 92 96
Completed [2] 92 96
Not Completed 8 9
Reason Not Completed
Did not consent to extended follow up             8             9
[1]
Subjects completed major endpoints; CMV disease and/or all-cause mortality
[2]
Subjects that completed major endpoint; CMV disease and/or all-cause mortality
Arm/Group Title Preemptive Therapy Prophylaxis Total
Hide 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 Number of Baseline Participants 100 105 205
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 100 participants 105 participants 205 participants
57
(49.5 to 62.5)
58
(51 to 63)
58
(50 to 63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 105 participants 205 participants
Female
35
  35.0%
27
  25.7%
62
  30.2%
Male
65
  65.0%
78
  74.3%
143
  69.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 105 participants 205 participants
Hispanic or Latino
8
   8.0%
11
  10.5%
19
   9.3%
Not Hispanic or Latino
92
  92.0%
94
  89.5%
186
  90.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants 105 participants 205 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   2.0%
2
   1.9%
4
   2.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   6.0%
3
   2.9%
9
   4.4%
White
90
  90.0%
99
  94.3%
189
  92.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   2.0%
1
   1.0%
3
   1.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 100 participants 105 participants 205 participants
100 105 205
Baseline absolute neutrophil count(ANC)   [1] 
Mean (Inter-Quartile Range)
Unit of measure:  Count per 1000 cells/µL
Number Analyzed 100 participants 105 participants 205 participants
6888
(3500 to 8640)
7409
(3600 to 9640)
7160
(3600 to 9325)
[1]
Measure Description: ANC collected prior to the initiation of intervention
1.Primary Outcome
Title Incidence of Cytomegalovirus (CMV) Disease.
Hide Description CMV disease as verified by an independent end point committee
Time Frame 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized subjects
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Number
Unit of Measure: participants
9 20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0396
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
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
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
Hide Description Survival probability at 1 year
Time Frame Up to 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat (ITT) population
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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
Overall Number of Participants Analyzed 100 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: survivor probabillity
.880
(.798 to .930)
.933
(.865 to .967)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments log-rank test for equality of survivor functions
Statistical Test of Hypothesis P-Value 0.19
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Incidence of Allograft Rejection
Hide Description Number of subjects with allograft rejection
Time Frame Up to 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
28
  28.0%
26
  24.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.60
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.45 to 1.58
Estimation Comments The odds of rejection in prophylaxis group compared to preemptive group
4.Secondary Outcome
Title Graft Loss
Hide Description Incidence of graft loss (re-transplantation)
Time Frame Up to 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
2
   2.0%
2
   1.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.96
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.13 to 6.92
Estimation Comments The odds of graft loss in prophylaxis group compared to preemptive group
5.Secondary Outcome
Title Late-onset CMV Disease
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
6
   6.0%
18
  17.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.24
Confidence Interval (2-Sided) 95%
1.21 to 8.69
Estimation Comments Odds of late disease in prophylaxis group compared to preemptive
6.Secondary Outcome
Title Bacterial Infections
Hide Description Incidence of bacterial opportunistic infections
Time Frame Up to 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
22
  22.0%
26
  24.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.64
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.61 to 2.23
Estimation Comments Odds of bacterial infection in prophylaxis subjects compared to preemptive
7.Secondary Outcome
Title Major Fungal Infections
Hide Description Opportunistic fungal infections
Time Frame Up to 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
4
   4.0%
9
   8.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.18
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
0.66 to 7.62
Estimation Comments Odds of fungal disease in prophylaxis group compared to preemptive
8.Secondary Outcome
Title Major Non-CMV Viral Infections
Hide Description Incidence of non-CMV viral infections
Time Frame Up to 365 days post-transplant
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
2
   2.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Neutropenia
Time Frame Day 1 through Day 107
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
36
  36.0%
35
  33.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
10.Secondary Outcome
Title Neutropenia Less Than 500
Hide Description ANC less than 500 while on valganciclovir
Time Frame prior to day 107
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
12
  12.0%
10
   9.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
11.Secondary Outcome
Title Hematopoietic Growth Factors
Hide Description Hematopoietic growth factor receipt for ANC less than 500 during valganciclovir treatment.
Time Frame Day 1 through Day 107
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Preemptive Therapy Prophylaxis
Hide 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.
Overall Number of Participants Analyzed 100 105
Measure Type: Count of Participants
Unit of Measure: Participants
5
   5.0%
7
   6.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Preemptive Therapy, Prophylaxis
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.61
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
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
Hide 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 (%) Affected / at Risk (%)
Total   12/100 (12.00%)      7/105 (6.67%)    
Show Serious Adverse Events Hide Serious Adverse Events
Preemptive Therapy Prophylaxis
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/100 (2.00%)      0/105 (0.00%)    
Cardiac disorders     
Pericardial effusion * 1  1/100 (1.00%)  1 0/105 (0.00%)  0
Renal and urinary disorders     
Kidney stone * 1  1/100 (1.00%)  1 0/105 (0.00%)  0
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Preemptive Therapy Prophylaxis
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/100 (1.00%)      1/105 (0.95%)    
Blood and lymphatic system disorders     
leukopenia  1  1/100 (1.00%)  1 1/105 (0.95%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
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.
Results Point of Contact
Name/Title: Nina Singh, MD
Organization: University of Pittsburgh - Medicine - Infectious Diseases
Phone: 412-360-1688
EMail: nis5@pitt.edu
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01552369     History of Changes
Other Study ID Numbers: 11-0073
First Submitted: March 2, 2012
First Posted: March 13, 2012
Results First Submitted: June 13, 2019
Results First Posted: July 2, 2019
Last Update Posted: July 2, 2019