Cytomegalovirus Prophylaxis With Letermovir in Heart Transplant Recipients

This protocol represents a Phase II pilot prospective non-randomized single arm open-label study design. We aim to enroll 30 patients after heart transplantation (Study Group), who will meet all of the inclusion and none of the exclusion criteria and 60 propensity-matched historical controls (Controls; matched for gender, age, CMV serological status, CMV DNA quantification method, donor and transplant data and immunosuppresion treatment). All patients in the Study Group will receive virostatic prophylaxis with letermovir 480 mg qd (We will be utilizing Letermovir oral formulation of 240 mg or 480 mg as available). Patients in Controls will receive virostatic prophylaxis with valgancyclovir 450 mg bid. In all patients the virostatic prophylaxis will be initiated between days 4 and 7 after heart transplantation and the duration of virostatic prophylaxis will be determined by the Quantiferon-CMV assay. In all patients, initial Quantiferon-CMV assay evaluation will be performed 100 days post-heart transplant at which time PCR CMV assay will also be made. In patients with negative PCR CMV and Quantiferon-CMV values ≥ 0,2 IU/mL the virostatic therapy will be discontinued \[10\]. In patients with negative PCR CMV and Quantiferon-CMV values \< 0,2 IU/mL the virostatic prophylaxis will continue for additional 30 days at which point Quantiferon-CMV assay will be re-evaluated. In an event of CMV infection/disease CMV it will be treated using valgancyclovir (900 mg q12) or gancyclovir (5 mg/kg q12h) per discretion of the treating heart transplant cardiologist and resistance to virostatic therapy will be tested at this time point. All patients (Study Group and Controls) will receive immunosuppresion induction therapy and triple maintenance immunosuppression therapy (TAC/MMF/steroid), fungal (posaconazole - 6 months), and pneumocystis prophylaxis (TMP/SMX - lifelong). In the Study Group additional, HSV /VZV viral prophylaxis with valacyclovir (500 mg q12, adjusted for renal function) will be used for 6 months after heart transplantation. Patients will be followed on an outpatient basis monthly for 12 months after enrollment and the events will be recorded using the following definitions. The maximum expected duration of letermovir therapy in the Study Group will be equal to the duration of follow-up - 12 months. After completion of the study all patients in the Study Group that may still require CMV virostatic prophylaxis according to our institutional guidelines will be switched to the current standard of care at our institution - valgancyclovir.