protocolSection identificationModule nctId: NCT06339892, orgStudyIdInfo id: 2022-3.11/451, briefTitle: HCMV Breakthrough Infections During Letermovir Prophylaxis, acronym: CMVbreak, statusModule overallStatus: RECRUITING, startDateStruct date: 2023-01-09, primaryCompletionDateStruct date: 2025-06, completionDateStruct date: 2026-03, studyFirstPostDateStruct date: 2024-04-01, lastUpdatePostDateStruct date: 2024-04-01, sponsorCollaboratorsModule leadSponsor name: Foundation IRCCS San Matteo Hospital, class: OTHER, collaborators name: Ministero della Salute, Italy, descriptionModule briefSummary: The goal of this clinical trial is to compare two strategies to monitor human cytomegalovirus (HCMV) infections in transplanted patients receiving letermovir (LTV) as anti-HCMV prophylaxis.HCMV infection after transplantation is diagnosed by detection of HCMV DNA in blood. However, due to the peculiar mechanism of action of LTV, most episodes of HCMV DNA detection are caused by release in the blood stream of non-infectious HCMV DNA.In true episodes of productive infection, HCMV DNA in blood is present inside the virion and therefore is resistant to DNAse digestion. Conversely, when non-infectious free-floating HCMV DNA is released in the bloodstream, it will be degraded after treatment of plasma with DNAse and will not be detectable by real-time PCR assays.Researchers will compare determination of HCMV DNA in blood with or without previous digestion of non-infectious free-floating DNA with DNAse.In patients of the Control group HCMV DNA will be tested without DNAse digestion. If HCMV DNA is positive, patients will stop LTV prophylaxis and receive antiviral therapy with another drug.In patients of the Study group HCMV DNA will be tested after DNAse digestion. Only if HCMV DNA is positive after DNAse digestion, patients will stop LTV prophylaxis and receive antiviral therapy with another drug.The main aim of the study is to demonstrate that, by avoiding inappropriate antiviral therapy during LTV prophylaxis, transplant patients will suffer of lower antiviral-drug-related toxicity. A monitoring strategy able to identify true episodes of HCMV productive infection during LTV prophylaxis will lead to a lower rate of inappropriate antiviral therapy and drug-related toxicity without an increased risk of HCMV disease., conditionsModule conditions: Cytomegalovirus Infections, conditions: Cytomegalovirus Viremia, conditions: Hematopoietic Stem Cell Transplantation, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, primaryPurpose: DIAGNOSTIC, maskingInfo masking: NONE, enrollmentInfo count: 140, type: ESTIMATED, armsInterventionsModule interventions name: Determination of HCMV DNA in plasma after DNAse digestion., interventions name: Determination of HCMV DNA in blood or plasma., outcomesModule primaryOutcomes measure: - Proportion of patients with positive HCMV DNAemia developing antiviral drug-related toxicity., secondaryOutcomes measure: Proportion of patients developing HCMV DNAemia during LTV prophylaxis., secondaryOutcomes measure: Proportion of patients developing HCMV disease within day 100 and between day 100 and 360 from transplant (key secondary endpoint), secondaryOutcomes measure: Proportion of patients stopping LTV prophylaxis and shifting to GCV/VGCV/FOS therapy., secondaryOutcomes measure: Proportion of patients requiring GCV/VGCV/FOS therapy between day 100 and 360., secondaryOutcomes measure: Proportion of patients with persisting HCMV DNAemia., secondaryOutcomes measure: Proportion of patients developing neutropenia between day 100 and 360., secondaryOutcomes measure: Proportion of patients developing HCMV-specific T-cell response at day 100, 180, and 360., secondaryOutcomes measure: Proportion of patients developing LTV-resistant HCMV strains., secondaryOutcomes measure: Cumulative incidence of acute or chronic GvHD., secondaryOutcomes measure: Transplant related mortality (TRM), underlying disease relapse, and 1-year survival., eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: ASST-Spedali Civili, status: RECRUITING, city: Brescia, state: BS, country: Italy, contacts name: Michele Malagola, MD, role: CONTACT, geoPoint lat: 45.53558, lon: 10.21472, locations facility: Fondazione IRCCS Policlinico San Matteo, status: RECRUITING, city: Pavia, state: PV, zip: 27100, country: Italy, contacts name: Daniele Lilleri, MD, role: CONTACT, phone: +39 0382 502420, email: d.lilleri@smatteo.pv.it, contacts name: Irene Cassaniti, PhD, role: CONTACT, phone: +39 0382 502420, email: i.cassaniti@smatteo.pv.it, geoPoint lat: 45.19205, lon: 9.15917, locations facility: ASST-Ospedale Papa Giovanni XXIII, status: NOT_YET_RECRUITING, city: Bergamo, country: Italy, contacts name: Alessandra Algarotti, MD, role: CONTACT, geoPoint lat: 45.69601, lon: 9.66721, locations facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna, status: NOT_YET_RECRUITING, city: Bologna, country: Italy, contacts name: Francesca Bonifazi, MD, role: CONTACT, geoPoint lat: 44.49381, lon: 11.33875, locations facility: ASST Grande Ospedale Metropolitano Niguarda, status: NOT_YET_RECRUITING, city: Milano, country: Italy, contacts name: Arianna Pani, MD, role: CONTACT, geoPoint lat: 45.46427, lon: 9.18951, locations facility: Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", status: NOT_YET_RECRUITING, city: Reggio Calabria, country: Italy, contacts name: Barbara Loteta, MD, role: CONTACT, geoPoint lat: 38.11047, lon: 15.66129, locations facility: AOU Policlinico Umberto I, status: NOT_YET_RECRUITING, city: Roma, country: Italy, contacts name: Corrado Girmenia, MD, role: CONTACT, geoPoint lat: 41.89193, lon: 12.51133, locations facility: Policlinico Universitario Agostino Gemelli, status: NOT_YET_RECRUITING, city: Roma, country: Italy, contacts name: Patrizia Chiusolo, MD, role: CONTACT, geoPoint lat: 41.89193, lon: 12.51133, hasResults: False