2026-04-13T03:04:24Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/130892025-10-24T10:30:23Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Paez-Vega, Aurora author Vaquero Barrios, José Manuel author Ruiz-Arabi, Elisa author Iturbe, David author Alonso Moralejo, Rodrigo author Ussetti, Piedad author Monforte, Victor author Berastegui Garcia, Cristina author 2025-05-15T07:37:19Z 2025-05-15T07:37:19Z 2025-05 Cytomegalovirus infection; Immunoguided prophylaxis; Lung transplantation Infecció per citomegalovirus; Profilaxi immunoguiada; Trasplantament de pulmó Infección por citomegalovirus; Profilaxis inmunoguiada; Trasplante de pulmón Background The standard prophylaxis treatment for cytomegalovirus (CMV) disease in CMV-seropositive lung transplant recipients is six months of prophylaxis with valganciclovir followed by six months of pre-emptive therapy. This protocol is associated with adverse events and risk of resistance. We have previously shown that prophylaxis can be suspended in CMV-seropositive kidney transplant recipients receiving thymoglobulin without increasing the risk of CMV disease and reducing the incidence of neutropenia. The objective of the current study is to demonstrate that immunoguided prophylaxis is effective and safe in seropositive lung transplant recipients. Methods A phase III, multicentre, randomised, open-label, noninferiority clinical trial was conducted in adult lung transplant recipients. Patients were randomised (1:1) to two groups: (1) immunoguided prophylaxis (IP), consisting of 3 months of universal prophylaxis followed by CMV-specific cell-mediated immunity-guided discontinuation, or (2) standard prophylaxis (SP), consisting of 6 months of prophylaxis followed by pre-emptive therapy, both for a total of 12 months. The noninferiority margin was 7%. The primary and secondary efficacy endpoints were CMV disease and asymptomatic CMV replication at month 18. The primary and secondary safety endpoints were incidence of neutropenia (defined as neutrophil count <1500 cells/μL), incidence of rejection and number of days of valganciclovir prophylaxis. This trial was registered in EudraCT (2018-003300-39) and ClinicalTrials.gov (NCT03699254). This trial has been completed. Findings Patients were recruited between April 2019 and December 2021 in seven Spanish centres. A total of 150 patients were randomised (75 patients per group). Incidence of CMV disease at month 18 did not differ among groups (18·7% [14 patients] vs. 16·0% [12 patients]; risk difference [RD] −0·03 [95% CI −0·15% to 0·06%]; P = 0·620) but occurred earlier in the IP group compared to the SP group. The proportion of patients who developed CMV disease at ≤180 days after transplant was higher in the IP group compared with the SP group (8% [6 patients] vs. 0% [0 patients]; RD −0·08 [95% CI −0·14 to −0·02; P = 0·009]). Asymptomatic CMV replication was reduced in the IP group vs. the SP group (4·0% [3 patients] vs. 16·0% [12 patients]; adjusted RD 0·12 [95% CI 0·03–0·21; P = 0·009]). A total of 30 patients (40%) in the IP group did not require prophylaxis from month 4 to 12. No significant difference was observed in the proportion of patients with neutropenia during months 4 to 7 (14·7% [11 patients] vs. 25·3% [19 patients]; RD 0·11 [95% CI −0·02 to 0·23]; P = 0·090) or rejection (33·3% [25 patients] vs. 30·7% [23 patients]; RD −0·03 [95% CI −0·18 to 0·12; P = 0·690]). The median days of valganciclovir was lower in the IP group than in the SP group (137 [92–266] vs. 198 [173–281]; P < 0.001). Interpretation Immunoguided prophylaxis was noninferior to the standard of care in preventing CMV disease in lung transplant recipients. It could be considered for implementing in clinical practice in CMV-seropositive lung transplant recipients upon considering the study limitations. Carlos III Health Institute, the SATOT Research Grant, the CIBER (Biomedical Network Research Centre Consortium), the Ministry of Science and Innovation, and the European Union. http://hdl.handle.net/11351/13089 Avaluació de resultats (Assistència sanitària) Pulmons - Trasplantació Medicaments antivírics - Ús terapèutic Infeccions per citomegalovirus - Prevenció Infeccions per citomegalovirus - Tractament ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome DISEASES::Virus Diseases::DNA Virus Infections::Herpesviridae Infections::Cytomegalovirus Infections Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Surgical Procedures, Operative::Thoracic Surgical Procedures::Pulmonary Surgical Procedures::Lung Transplantation ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Drug Therapy::Chemoprevention::Antibiotic Prophylaxis CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents Other subheadings::Other subheadings::/therapeutic use TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Herpesviridae::infecciones por Citomegalovirus Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::intervenciones quirúrgicas::procedimientos quirúrgicos torácicos::procedimientos quirúrgicos pulmonares::trasplante de pulmón TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::farmacoterapia::quimioprevención::profilaxis antibiótica COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos Otros calificadores::Otros calificadores::/uso terapéutico Safety and efficacy of immunoguided prophylaxis for cytomegalovirus disease in low-risk lung transplant recipients in Spain: a multicentre, open-label, randomised, phase 3, noninferiority trial