CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")
Condition: Cytomegalovirus Infection
MeSH terms: Cytomegalovirus Infections
Intervention: Valganciclovir
Intervention description: 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.
Intervention MeSH terms: Valganciclovir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 205.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: CMV; cytomegalovirus infections; ganciclovir; liver transplant; preemptive therapy; prophylaxis; valganciclovir

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.
    

Eligibility 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.