ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Active, not recruiting
First Posted : March 13, 2012
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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 Type : Interventional  (Clinical Trial)
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 : October 29, 2012
Estimated Primary Completion Date : June 30, 2018
Estimated Study Completion Date : July 30, 2018


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.



Primary Outcome Measures :
  1. Incidence of Cytomegalovirus (CMV) disease [ Time Frame: Up to 365 days post-transplant ]

Secondary Outcome Measures :
  1. All-cause mortality [ Time Frame: Up to 365 days post-transplant ]
  2. Incidence of allograft rejection [ Time Frame: Up to 365 days post-transplant ]
  3. Incidence of graft loss (re-transplantation) [ Time Frame: Up to 365 days post-transplant ]
  4. Incidence of late-onset CMV disease (occurring after 100 days post-randomization) [ Time Frame: Up to 365 days post-transplant ]
  5. Incidence of major bacterial infections [ Time Frame: Up to 365 days post-transplant ]
  6. Incidence of major fungal infections [ Time Frame: Up to 365 days post-transplant ]
  7. Incidence of major non-CMV viral infections [ Time Frame: Up to 365 days post-transplant ]
  8. Incidence of neutropenia (Absolute Neutrophil Count (ANC) <1,000 and <500/microlitres) [ Time Frame: Day 1 through Day 107 ]
  9. Incidence of receipt of hematopoietic growth factor [ Time Frame: Day 1 through Day 107 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

  6. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01552369


Locations
United States, California
Ronald Reagan University of California Los Angeles Medical Center
Los Angeles, California, United States, 90095-8358
United States, Georgia
Emory Clinic - Transplant Center
Atlanta, Georgia, United States, 30322-1013
United States, Minnesota
Mayo Clinic, Rochester - Infectious Diseases
Rochester, Minnesota, United States, 55905-0001
United States, New York
Mount Sinai School of Medicine - Medicine - Infectious Diseases
New York, New York, United States, 10029-6504
United States, Pennsylvania
University of Pittsburgh - Medicine - Infectious Diseases
Pittsburgh, Pennsylvania, United States, 15213-3403
United States, Washington
University of Washington - Medicine
Seattle, Washington, United States, 98195-7110
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01552369     History of Changes
Other Study ID Numbers: 11-0073
First Posted: March 13, 2012    Key Record Dates
Last Update Posted: April 3, 2018
Last Verified: March 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
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Valganciclovir
Ganciclovir
Antiviral Agents
Anti-Infective Agents