Immunoguided discontinuation of prophylaxis for cytomegalovirus disease in kidney transplant recipients treated with antithymocyte globulin: A randomized clinical trial
| Autor: | Alberto Rodríguez-Benot, Mario Fernández-Ruiz, Jorge Valle-Arroyo, María O. López-Oliva, Belén Gutiérrez-Gutiérrez, Marta Crespo, Ibai Los-Arcos, Julián Torre-Cisneros, Juan Carlos Ruiz San Millán, Patricia Muñoz, Sara Cantisán, María Ángeles Lobo-Acosta, José C. Garrido-Gracia, M.L. Agüera, Luis Guirado, Miguel Montejo, Cristian Rodelo-Haad, Dolores Redondo-Pachón, Domingo Hernández, Angela Cano, Jose Yuste, Carme Facundo, Aurora Páez-Vega, Marta Suñer, Cristina Galeano-Álvarez, Elisa Vidal |
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| Přispěvatelé: | Instituto de Salud Carlos III, Sociedad Española de Nefrología, Red Española de Investigación en Patología Infecciosa, European Commission, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (España), Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Microbiology (medical)
kidney transplant medicine.medical_specialty Congenital cytomegalovirus infection Cytomegalovirus Disease Neutropenia Antiviral Agents law.invention Randomized controlled trial antithymocyte globulin law Internal medicine medicine Humans cytomegalovirus infection Kidney transplant Ganciclovir Antilymphocyte Serum QuantiFERON-CMV assay business.industry Incidence (epidemiology) Valganciclovir medicine.disease Kidney Transplantation Transplant Recipients Cytomegalovirus infection Discontinuation Clinical trial Infectious Diseases Cytomegalovirus Infections CMV-specific cell-mediated immunity Antithymocyte globulin business medicine.drug |
| Popis: | [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. This work was supported by the 2013–2016 National R&D&I Plan and the Carlos III Health Institute (grantPI15/00402 to J.T.C.). It also had the support of The Spanish Society of Nephrology (grant S.E.N. to C.F.), as well as support from the National R&D&I Plan 2013–2016 and the Carlos III Health Institute, General Sub-Directorate of Networks and Cooperative Research Centres, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/000, RD16/0016/0003, RD16/0016/0007, RD16/0016/0008, RD16/0016/0009 and RD16/0016/0012), co-financed by the European Regional Development Fund “A way to achieve Europe,” Operational Programme Intelligent Growth 2014–2020; Spanish Network for Renal Disease Research (RedInRen, RD16/0009/0006, RD16/0009/0008, RD16/0009/0013, RD16/0009/0014, RD16/0009/0019, RD16/0009/0027, RD16/0009/0034); CIBERES (CB06/06/0058); the Spanish Group for the Study of Infection in Transplantation and the Immunosuppressed Host of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and Spanish Clinical Research Network funded by the ISCIII-Subdirectorate General for the Evaluation and Promotion of Research through projects PT13/0002/0010-PT17/0017/0012 and PT13/0002/0014-PT17/0017/0032 integrated in the 2013–2016 National R&D&I Plan and by the National Plan for Scientific and Technical Research and Innovation (2017–2020) and co-financed by the European Regional Development Fund. |
| Databáze: | OpenAIRE |
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