Maribavir for Preemptive Treatment of Cytomegalovirus Reactivation.
Maertens, J., Cordonnier, C. et al. (2019).New England Journal of Medicine 381(12): 1136-1147.
Aims
This study aimed to evaluate the safety, side-effect profile and antiviral activity of different doses of maribavir as compared with valganciclovir for preemptive treatment of Cytomegalovirus (CMV) infection among hematopoietic-cell and solid-organ transplant recipients without CMV organ disease.
Interventions
Patients were randomized to receive oral maribavir (Shire) at a dose of 400mg, 800mg, or 1200mg twice daily or valganciclovir (Roche) at a dose of 900mg twice daily for weeks 1 through 3 and 900mg once daily after week 3 (with dose adjustment for renal function).
Participants
161 recipients of hematopoietic-cell or solid-organ transplants (≥18 years of age, with CMV reactivation (1000 to 100,000 DNA copies per milliliter)).
Outcomes
The primary efficacy end point was the percentage of patients with a response to treatment, defined as confirmed undetectable CMV DNA in plasma, within 3 weeks and 6 weeks after the start of treatment. The primary safety end point was the incidence of adverse events that occurred or worsened during treatment.
Follow-up
12 weeks
CET Conclusions
This is a phase II open-label randomised controlled trial that was well conducted and reported. Patients with re-activated CMV with a screening CMV DNA level of 1,000 to 100,000 copies/ml were randomised to one of four arms: Mirabavir BD at 400mg, 800mg or 1200mg or Valganciclovir 900mg BD and treatment was given for up to 12 weeks. The study showed a very similar efficacy between Maribavir and Valganciclovir in response to treatment within 3 weeks and within 6 weeks. There was a slight difference in some adverse events that occurred more with Maribavir than Valganciclovir (dysgeusia, gastrointestinal events, and elevated immunosuppressant drug levels). Neutropenia was less frequent with Maribavir than Valganciclovir however. More studies are required given the potential uses for a drug that does not have to be adjusted for renal function and might cause less neutropenia than Valganciclovir.
Data analysis
Modified intention-to-treat analysis
Trial registration
N/A