CMV Antiviral Prevention Strategies in D+R-Liver Transplants ("CAPSIL")
Condition: Cytomegalovirus Infection
MeSH terms: Cytomegalovirus Infections
Study type: Interventional
Phase: Phase 4

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.
    

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).
    

Intervention name(s): Valganciclovir
Intervention type(s): Drug
Intervention description(s): 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
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CMV; cytomegalovirus infections; ganciclovir; liver transplant; preemptive therapy; prophylaxis; valganciclovir