Maribavir vs. Valganciclovir for CMV Prophylaxis in High-Risk Kidney Transplant Recipients

Maribavir has been evaluated for the prevention of CMV infection in Phase II and Phase III trials within allogeneic stem cell transplant recipients. At 6-months post-transplant, the rates of CMV infection using PCR were not different between treatment and placebo arms, although the rates of pp65 antigenemia were lower in the Maribavir group. However, these studies used a low dose of 100mg PO BID. In subsequent studies within solid organ transplantation, Maribavir dosed at 400 to 1200mg PO BID was equally efficacious to valganciclovir for the treatment of CMV infection. Of note and importance to this proposal, the rates of neutropenia were 4-5% in the Maribavir treated patients vs. 15-18% in Valganciclovir patients. Thus, at an appropriate dose, Maribavir appears to have similar efficacy to Valganciclovir in treating CMV infection with a significantly reduced incidence of neutropenia. Currently, there is a lack of randomized controlled trials assessing the safety and efficacy of adequately dosed (=400mg PO BID) Maribavir for the prevention of CMV infection in solid organ transplant recipients.

Aim 1. Assess the incidence of leukopenia in those randomized to Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection.

Hypothesis 1. The incidence of clinically meaningful leukopenia, defined as a WBC count of \< 3,000 cells/mm3 and a reduction in total mycophenolate dose below 1,500 mg/day or valganciclovir dose below 900mg per day (adjusted for renal function), will be significantly lower in the Maribavir arm, as compared to the Valganciclovir arm.

Aim 2. Assess the efficacy of Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection.

Hypothesis 2. The incidence of CMV infection and disease will be similar between the Maribavir arm, as compared to the Valganciclovir arm, at 3-, 6-, and 12-months post-transplant.

Aim 3. Assess the impact of Maribavir vs. Valganciclovir prophylaxis on healthcare utilization and costs in adult kidney transplant recipients at high-risk of CMV infection.

Hypothesis 3. Healthcare utilization will be lower in the Maribavir arm, as compared to the Valganciclovir arm, at 6- and 12-months post-transplant, driven predominantly by reduced number of telephone calls, televisits, and laboratory monitoring encounters.

Exploratory Aim 4. Assess the impact of Maribavir vs. Valganciclovir prophylaxis in adult kidney transplant recipients at high-risk of CMV infection on patient-reported outcomes for quality of life and satisfaction.