Aurora Páez-Vega1,2, Belén Gutiérrez-Gutiérrez2,3, Maria L Agüera1,4, Carme Facundo5, Dolores Redondo-Pachón6, Marta Suñer7, Maria O López-Oliva8, Jose R Yuste2,9, Miguel Montejo2,10, Cristina Galeano-Álvarez11, Juan C Ruiz-San Millan12, Ibai Los-Arcos2,13, Domingo Hernández14, Mario Fernández-Ruiz2,15, Patricia Muñoz16, Jorge Valle-Arroyo1,2, Angela Cano1,2, Alberto Rodríguez-Benot1,4, Marta Crespo6, Cristian Rodelo-Haad1,4, María A Lobo-Acosta17, Jose C Garrido-Gracia18, Elisa Vidal1,2,19, Luis Guirado5, Sara Cantisán1,2, Julian Torre-Cisneros1,2,19. 1. Maimónides Institute for Biomedical Research of Cordoba (IMIBIC)/Reina Sofía University Hospital/University of Cordoba (UCO), Cordoba, Spain. 2. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0002, RD16/0016/0003, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009 and RD16/0016/0012), Instituto de Salud Carlos III, Madrid, Spain. 3. Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine. Virgen Macarena University Hospital/ University of Seville. Biomedicine Institute of Seville (IBiS), Seville, Spain. 4. Nephrology Service, Reina Sofia University Hospital, RedInRen (RD16/0009/0034), Cordoba, Spain. 5. Renal Transplant Unit, Nephrology Service, Fundació Puigvert, Institut Investigació Biosanitaria Sant Pau, Autonomous University of Barcelona (UAB), RedInRen (RD16/0009/0019), Barcelona, Spain. 6. Nephrology Service, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), RedInRen (RD16/0009/0013), Barcelona, Spain. 7. Nephrology Service, Virgen del Rocío University Hospital, Seville, Spain. 8. Nephrology Service, La Paz University Hospital, RedInRen (RD16/0009/0008), Madrid, Spain. 9. Infectious Diseases Unit, Clinic University of Navarra, Pamplona, Spain. 10. Infectious Diseases Service, Cruces University Hospital, Bilbao, Spain. 11. Nephrology Service, Ramón y Cajal University Hospital, IRYCIS, RedInRen (RD16/0009/0014), Madrid, Spain. 12. Nephrology Service, Marqués de Valdecilla Hospital, University of Cantabria, IDIVAL, RedInRen (RD16/0009/0027), Santander, Spain. 13. Infectious Diseases Service, Vall d' Hebron University Hospital, Barcelona, Spain. 14. Nephrology Service, Carlos Haya Regional University Hospital, Institute for Biomedical Research of Malaga (IBIMA), Universidad of Malaga, RedInRen (RD16/0009/0006), Malaga, Spain. 15. Infectious Diseases Unit, 12 de Octubre University Hospital, Health Research Institute (imas12), Madrid, Spain. 16. Department of Clinical Microbiology and Infectious Diseases, Gregorio Marañon University Hospital, Madrid, Spain. Gregorio Marañón Biomedical Research Institute, Madrid, Spain. Department of Medicine, Complutense University of Madrid, Madrid, Spain. CIBERES (CB06/06/0058), Madrid, Spain. 17. Clinical Trials Unit, Virgen del Rocio University Hospital (CTU-HUVR), (SCReNPT13/0002/0010-PT17/0017/0012). Seville, Spain. 18. Clinical Trials Unit, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC)/Reina Sofia University Hospital/University of Cordoba (SCReN PT13/0002/0014, PT17/0017/0032), Cordoba, Spain. 19. Infectious Diseases Service, Reina Sofia University Hospital, Cordoba, Spain.
Abstract
BACKGROUND: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. METHODS: In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). RESULTS: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. CONCLUSIONS: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. CLINICAL TRIALS REGISTRATION: NCT03123627.
BACKGROUND: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. METHODS: In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). RESULTS: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. CONCLUSIONS: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. CLINICAL TRIALS REGISTRATION: NCT03123627.
Authors: Ambreen Azhar; Makoto Tsujita; Manish Talwar; Vasanthi Balaraman; Anshul Bhalla; James D Eason; Simonne S Nouer; Keiichi Sumida; Adam Remport; Isaac E Hall; Randi Griffin; George Rofaiel; Miklos Z Molnar Journal: Ren Fail Date: 2022-12 Impact factor: 3.222