Oliver Witzke1, Martin Nitschke2, Michael Bartels3, Heiner Wolters4, Gunter Wolf5, Petra Reinke6, Ingeborg A Hauser7, Ulrich Alshuth8, Volker Kliem9. 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.
Abstract
BACKGROUND: 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. METHODS: 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+). RESULTS: 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 m) were not significantly different between prophylaxis and preemptive treatment. Tolerability was comparable between groups. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: 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. METHODS: 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+). RESULTS: 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 m) were not significantly different between prophylaxis and preemptive treatment. Tolerability was comparable between groups. CONCLUSIONS: 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.
Authors: Caleb Skipper; Mark R Schleiss; Ananta S Bangdiwala; Nelmary Hernandez-Alvarado; Kabanda Taseera; Henry W Nabeta; Abdu K Musubire; Sarah M Lofgren; Darin L Wiesner; Joshua Rhein; Radha Rajasingham; Charlotte Schutz; Graeme Meintjes; Conrad Muzoora; David B Meya; David R Boulware Journal: Clin Infect Dis Date: 2020-07-27 Impact factor: 9.079
Authors: Anne-Grete Märtson; Martijn Bakker; Hans Blokzijl; Erik A M Verschuuren; Stefan P Berger; Lambert F R Span; Tjip S van der Werf; Jan-Willem C Alffenaar Journal: BMJ Open Date: 2020-01-07 Impact factor: 2.692
Authors: Hana Rohn; Rafael Tomoya Michita; Esther Schwich; Sebastian Dolff; Anja Gäckler; Mirko Trilling; Vu Thuy Khanh Le-Trilling; Benjamin Wilde; Johannes Korth; Falko M Heinemann; Peter A Horn; Andreas Kribben; Oliver Witzke; Vera Rebmann Journal: Front Immunol Date: 2018-05-08 Impact factor: 7.561