The VIPP study compared valganciclovir prophylaxis with preemptive treatment regarding efficacy, safety, and long-term graft outcome in cytomegalovirus (CMV)-positive (R+) renal transplant recipients.
Multicenter, open-label, randomized clinical study with a 12-month study phase and a follow-up of up to 84 months. Patients in the prophylaxis group received 2 × 450 mg/d oral valganciclovir for 100 days adjusted to renal function. Preemptive treatment with 2 × 900 mg/d valganciclovir was initiated at a viral load of 400 CMV copies/mL or greater (polymerase chain reaction) and maintained over ≥14 days, followed by secondary prophylaxis. Patients were stratified by donor CMV IgG serostatus (donor CMV IgG positive [D+]/R+, donor CMV IgG negative [D−]/R+).
The 12-month results were reported previously (Witzke et al Transplantation 2012). The intent-to-treat/safety population comprised 148 patients in the prophylaxis (61.5% D+/R+) and 151 patients in the preemptive group (52.3% D+/R+). Overall, 47% patients completed the follow-up. Significantly fewer patients in the prophylaxis compared with preemptive group experienced a CMV infection or disease up to month 84 (11.5%; 95% confidence interval [95% CI], 6.8-17.8%] vs 39.7%; 95% CI, 31.9-48.0%; P < 0.0001 and 4.7%; 95% CI, 1.9-9.5% vs 15.9%; 95% CI, 10.5-22.7%; P = 0.002). Incidences of graft loss (7.4% vs 8.6%), death (9.5% vs 11.3%), rejection (29.1% vs 28.5%), and renal function (estimated glomerular filtration rate [mean ± SD]: 58.2 ± 26.3 vs 59.9 ± 25.7 mL/min per 1.73 m2) were not significantly different between prophylaxis and preemptive treatment. Tolerability was comparable between groups.
Prophylaxis was more effective than the preemptive approach, applying a low-intense surveillance protocol in preventing CMV infection and disease in intermediate-risk patients. Both strategies were similarly effective in preventing graft loss and death under the conditions of this long-term trial with a threshold of 400 copies/mL for initiation of anti-CMV treatment.
In renal transplant recipients, 7-year follow up of a randomized clinical trial demonstrates that a strategy of prophylaxis is more effective than a preemptive strategy to prevent CMV infection and disease, but both strategies are similarly effective in preventing graft loss and death.
1 Department of Infectious Diseases and Department of Nephrology, University Duisburg‐Essen, Essen, Germany.
2 Transplantation Center, Medical Clinic I, University Hospital Schleswig-Holstein, Luebeck, Germany.
3 Department of General and Visceral Surgery, Helios Park Hospital, Leipzig, Germany.
4 Department of General and Visceral Surgery, University Hospital Muenster, Muenster, Germany.
5 MHBA Division of Nephrology, Department of Internal Medicine III, University Hospital Jena, Jena, Germany.
6 Department of Nephrology and Internal Intensive Care, Charité University Medicine Berlin, Berlin, Germany.
7 Department of Nephrology/Medical Clinic III, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.
8 Roche Pharma AG, Medical Management Established Products, Grenzach-Wyhlen, Germany.
9 Department of Internal Medicine and Nephrology, Nephrology Center of Lower Saxony, Klinikum Hann. Muenden, Hann, Muenden, Germany.
Received 27 July 2017. Revision received 2 October 2017.
Accepted 21 October 2017.
ClinicalTrials.gov Identifier: NCT00372229.
The VIPP study was sponsored by Roche Pharma AG, Grenzach-Wyhlen, Germany.
The authors declare no conflicts of interest.
O.W. and M.N. contributed to data acquisition, data analysis and interpretation, manuscript preparation/editing, and manuscript review. M.B., H.W., and G.W. contributed to data acquisition, data interpretation, and manuscript review. I.A.H. contributed to the design of the study, data acquisition, data analysis and interpretation, and manuscript review. P.R. contributed to the design of the study, data acquisition, data interpretation, and manuscript review. U.A. contributed to data analysis and interpretation, manuscript preparation/editing, and manuscript review. V.K. contributed to the design of the study, data acquisition, data analysis and interpretation, manuscript editing, and manuscript review. O.W. has received research funds and/or honoraria for lectures and consultancy from Alexion, Astellas, Basilea, Bristol-Myers Squibb, Chiesi, Janssen-Cilag, MSD, Novartis, Pfizer, Roche and Shire. M.N. has received research funds and/or honoraria for lectures and consultancy from Alexion, Astellas, Chiesi, Roche and Sanofi-Aventis. M.B., H.W. and P.R. declare no conflict of interest. G.W. has received honoraria for lectures from Novartis and Roche. I.A.H. has received honoraria for lectures or travel grants from Alexion, Astellas, Chiesi, Hexal, Novartis, Roche, Sanofi and Teva. U.A. is an employee of Roche Pharma AG. V.K. has received honoraria for lectures from Astellas, DaVita, Pfizer, Raptor and Roche.
Correspondence: Oliver Witzke, MD, Department of Infectious Diseases, University Duisburg‐Essen, Hufelandstrasse 55, 45147 Essen, Germany. (Oliver.firstname.lastname@example.org).
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