Effect of Preemptive Therapy vs Antiviral Prophylaxis on Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors: A Randomized Clinical Trial.
Singh, N., et al.JAMA 2020; 323(14): 1378-1387.
Aims
The aim of this study was to examine whether preemptive therapy is more effective than antiviral prophylaxis in preventing cytomegalovirus (CMV) disease in recipients of liver transplant who were CMV-seronegative with CMV seropositive donors.
Interventions
Participants were randomly assigned at a 1:1 ratio to either the preemptive group or the antiviral prophylaxis group.
Participants
205 liver transplant recipients.
Outcomes
The primary endpoint was the incidence of CMV disease within 12 months post-transplant. The secondary endpoints included delayed onset of CMV disease, graft loss, mortality (all-causes) by 12 months, biopsy proven acute rejection, oppportunistic bacterial and fungal infections, neutropenia and the need for granulocyte colony-stimulating factor.
Follow-up
12 months
CET Conclusions
This is a well written report of a good quality randomised controlled trial. Liver transplant recipients who were CMV seronegative but receiving livers from CMV seropositive donors were randomised to valganciclovir prophylaxis for 100 days, or to pre-emptive therapy with weekly monitoring of CMV serum PCR for 100 days. The trial was not blinded due to the need to give pre-emptive therapy in one arm. Randomisation was 1:1 using a computer generated allocation in blocks of 4. The study was powered for a large expected difference in CMV disease (5% versus 20%) based upon previous studies. The study found a significant reduction in CMV disease within 12 months with per-emptive therapy compared to prophylaxis (9% versus 19%). The vast majority of disease occurred after the cessation of 100 days of prophylaxis, whereas in the pre-emptive arm the cases were evenly split between the first 100 days and the rest of the 12 month follow up. 81% of patients in the pre-emptive arm developed CMV viraemia within a median 24 days after transplant. Pre-emptive therapy was initiated within 2 days after detection of viraemia. There was no significant difference in the total amount of valganciclovir used between the two arms. There were no significant differences in the rates of rejection, other infections, graft loss or mortality. In this population the use of pre-emptive CMV therapy resulted in a lower incidence of CMV disease in the first 12 months compared to prophylaxis.
Data analysis
Strict intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01552369