Trial Outcomes & Findings for CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL") (NCT NCT01552369)

NCT ID: NCT01552369

Last Updated: 2021-08-26

Results Overview

CMV disease as verified by an independent end point committee

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 205 participants
• Primary outcome timeframe: 365 days post-transplant
• Results posted on: 2021-08-26

Participant Flow

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.

Participant milestones

Measure	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=100	Prophylaxis 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=105
Overall Study STARTED	100	105
Overall Study One Year	100	105
Overall Study Final Follow up	92	96
Overall Study COMPLETED	92	96
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Measure	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=100	Prophylaxis 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=105
Overall Study Did not consent to extended follow up	8	9

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Preemptive Therapy n=100 Participants 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	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction. n=105	Total n=205 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	58 years n=7 Participants	58 years n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	27 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	78 Participants n=7 Participants	143 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	92 Participants n=5 Participants	94 Participants n=7 Participants	186 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	90 Participants n=5 Participants	99 Participants n=7 Participants	189 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	100 participants n=5 Participants	105 participants n=7 Participants	205 participants n=5 Participants
Baseline absolute neutrophil count(ANC)	6888 Count per 1000 cells/µL n=5 Participants	7409 Count per 1000 cells/µL n=7 Participants	7160 Count per 1000 cells/µL n=5 Participants

PRIMARY outcome

Timeframe: 365 days post-transplant

Population: All randomized subjects

CMV disease as verified by an independent end point committee

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Incidence of Cytomegalovirus (CMV) Disease.	9 participants	20 participants

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Population: Intent to treat (ITT) population

Survival probability at 1 year

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
All-cause Mortality	.880 survivor probabillity Interval 0.798 to 0.93	.933 survivor probabillity Interval 0.865 to 0.967

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Number of subjects with allograft rejection

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Incidence of Allograft Rejection	28 Participants	26 Participants

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Population: ITT population

Incidence of graft loss (re-transplantation)

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Graft Loss	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Population: ITT population

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

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Late-onset CMV Disease	6 Participants	18 Participants

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Incidence of bacterial opportunistic infections

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Bacterial Infections	22 Participants	26 Participants

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Population: ITT population

Opportunistic fungal infections

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Major Fungal Infections	4 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 365 days post-transplant

Incidence of non-CMV viral infections

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Major Non-CMV Viral Infections	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 107

Population: ITT population

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

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Neutropenia	36 Participants	35 Participants

SECONDARY outcome

Timeframe: prior to day 107

Population: ITT population

ANC less than 500 while on valganciclovir

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Neutropenia Less Than 500	12 Participants	10 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 107

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

Outcome measures

Measure	Preemptive Therapy n=100 Participants 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.	Prophylaxis n=105 Participants 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Hematopoietic Growth Factors	5 Participants	7 Participants

Adverse Events

Preemptive Therapy

Serious events: 2 serious events

Other events: 1 other events

Deaths: 12 deaths

Prophylaxis

Serious events: 0 serious events

Other events: 1 other events

Deaths: 7 deaths

Serious adverse events

Measure	Preemptive Therapy n=100 participants at risk 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.	Prophylaxis n=105 participants at risk 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Renal and urinary disorders Kidney stone	1.0% 1/100 • Number of events 1 • 1 year 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'.	0.00% 0/105 • 1 year 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'.
Cardiac disorders Pericardial effusion	1.0% 1/100 • Number of events 1 • 1 year 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'.	0.00% 0/105 • 1 year 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'.

Other adverse events

Measure	Preemptive Therapy n=100 participants at risk 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.	Prophylaxis n=105 participants at risk 900 mg of Valganciclovir given orally once daily to subjects for 100 days post transplantation. All dosages adjusted for renal dysfunction.
Blood and lymphatic system disorders leukopenia	1.0% 1/100 • Number of events 1 • 1 year 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'.	0.95% 1/105 • Number of events 1 • 1 year 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'.

Additional Information

Nina Singh, MD

University of Pittsburgh - Medicine - Infectious Diseases

Phone: 412-360-1688

Email: nis5@pitt.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place