Less renal allograft fibrosis with valganciclovir prophylaxis for cytomegalovirus compared to high-dose valacyclovir: a parallel group, open-label, randomized controlled trial.Reischig T, Kacer M, et al.
BMC Infect Dis. 2018; 18(1):573.
To compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation, with the focus on chronic histologic damage within the graft.
Patients were randomized (1:1) to valganciclovir or valacyclovir prophylaxis for 3 months in the 2VAL Study.
119 patients were enrolled (valganciclovir, n=60; valacyclovir, n=59). Protocol biopsy at 3 years with sufficient material was available from 101 patients (valganciclovir, n=51; valacyclovir, n=50).
The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. Data analysis was in an ITT population. Secondary endpoints included intrarenal mRNA expression of profibrotic genes, chronic rejection, CMV DNAemia, CMV disease, biopsy-proven acute rejection, renal function, patient and graft survival (not censored for death), and other infections. Patient and graft survival was assessed at 4 years, with other variables at 3 years.
≥4 years after transplantation or until death.
In univariate analysis, this study showed that valganciclovir and valaciclovir for CMV prophylaxis in renal transplantation were associated with similar rates of IFTA on 3-year protocol biopsy. Despite randomisation, there was an imbalance in “high risk” donor distribution between the study arms. The authors subsequently carried out a multivariate analysis to reflect the higher proportion of “high risk” donors in the valganciclovir arm, and then did show a significant reduction in moderate-severe IFTA (OR=0.31, P=0.03). There was no significant difference in CMV disease or viraemia between the two groups, which was uniformly low. The study was not blinded, and the rate of IFTA in the control arm was possibly overestimated for the power calculation, explaining why the expected number of withdrawals could not be tolerated without risking an inconclusive result in the univariate analysis.
Previously assessed as Reischig, T et al. Clinical Journal of The American Society of Nephrology; 10: 294-304, 2015.
Australian New Zealand Clinical Trials Registry - ACTRN12610000016033.