Letermovir vs Valganciclovir in CMV R+ Kidney Transplant

The purpose of this study is to evaluate the efficacy and tolerability of letermovir compared to standard-of-care, valganciclovir, for the prevention of clinically significant cytomegalovirus (CMV) infection in CMV moderate risk adult kidney transplant recipients.

A 3:1 match of historical valganciclvoir:letermovir arm

• Matching criteria:

• Induction agent: lymphocyte-depleting (rabbit anti-thymocyte globulin or alemtuzumab) versus non-lymphocyte depleting (basiliximab)
• Delayed graft function (dialysis within one week of kidney transplant)
• MMF dose at de novo discharge (weight-based vs non-weight based)

Study Arms:

• Letermovir Arm:

  • Letermovir 480 mg PO daily starting POD 4 through 10 OR
  • Letermovir 240 mg PO daily if given concomitantly with cyclosporine, for 90 days
  • Will be given with acyclovir 400 mg PO BID (or 200 PO BID if CrCl <25) for 90 days

• Historical Arm:

  • Valganciclovir 450 mg PO daily (adjusted for renal function) for 90 days

    • CrCl 25-30: valganciclovir 450 mg PO q 48 h
    • CrCl <25: Valganciclovir 450 mg PO three times weekly

Outcomes:

• Primary Efficacy Objective:

  • Incidence of patients with clinically significant CMV infection at 12 months post kidney transplant in patients who received letermovir versus standard of care valganciclovir

    • Clinically Significant CMV Infection: CMV disease or symptomatic viremia requiring therapeutic intervention

• Secondary Objectives:

  • Tolerability:

    • Proportion of patients with leukopenia or neutropenia (composite) in patients who received letermovir versus standard of care valganciclovir
• Leukopenia: white blood cells < 3500 cells/uL

• Neutropenia: absolute neutrophil count < 1000 cells/uL

  • Intolerability or early drug discontinuation

• Proportion of patients who discontinue the study drug prematurely due to adverse events or intolerance

  o Efficacy:

  • Time-to clinically significant CMV infection (days)
  • Breakthrough CMV while on CMV prophylaxis

• CMV Viremia

  • Detection of CMV DNA in blood via PCR

• Clinically significant CMV infection

  • CMV resistance
• Detection of CMV strains with genotypic or phenotypic resistance to antiviral agents used in prophylaxis or treatment