Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: Long-term results after 7 years of a randomized clinical trial.
Witzke O, Nitschke M, et al.Transplantation 2017 [record in progress].
Aims
To provide long term results of a previous randomised controlled trial (RCT)* after an additional 6 years of follow-up, which compared valganciclovir prophylaxis with pre-emptive treatment therapy in cytomegalovirus (CMV) positive renal transplant recipients.
Interventions
Participants were previously randomised* to either oral valganciclovir (2x450 mg) per day starting within 14 days after transplantation until day 100 post-transplantation, versus pre-emptive oral valganciclovir (2x900 mg) initiated at a viral load of ≥400 CMV copies/mL and maintained over ≥14 days, followed by secondary prophylaxis.
Participants
299 adult CMV immunoglobulin G seropositive kidney transplant recipients receiving immunosuppression during the first 14 days after transplantation with a calcineurin inhibitor, mycophenolate mofetil, and steroids.
Outcomes
The primary outcomes measured were the proportions of patients with active CMV infection and CMV disease within 12 months, the urine proteomic pattern at month 12, and time to graft loss up to 84 months. Secondary outcomes included proportions of patients with active CMV infection and disease during follow-up, acute graft rejection, patient survival, graft loss, renal function at month 12 and during follow-up, and adverse events.
Follow-up
Up to 84 months (7 years)
CET Conclusions
The VIPP study compared general prophylaxis versus preemptive therapy using oral valganciclovir in kidney transplant recipients with a positive CMV serostatus (both D+/R+ and D-/R+ patients) in terms of CMV infection and disease rates. The trial was supported by Roche and this article reports up to 7 year follow-up data. Prophylaxis consisted of 2x450 mg oral valganciclovir/day for 100 days adjusted to renal function. Patients randomised to the preemptive group were monitored by CMV-polymerase chain reaction (PCR) and preemptive treatment of 2x900mg/day was started at a viral load of ≥400 CMV copies/mL for at least 14 days followed by secondary prophylaxis. Both the intention to treat analysis which included all randomised patients, and the per protocol analysis were presented. The primary outcomes, i.e. the incidence of CMV infections or disease showed a significantly lower rate in the prophylaxis group compared to the preemptive group throughout the 7 year study period. There were also no differences between groups for any of the secondary outcomes, i.e. graft loss, death, rejection, renal function and adverse events.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously assessed as *Witzke O, et al. Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: 1-Year Results of a Randomized Clinical Trial. Transplantation. 2012;93(1):61-68.
Trial registration
Clinicaltrials.gov - NCT00372229