Cytomegalovirus InfectionsReCySOHTNCT05234723
Ganciclovir Resistant/Refractory Cytomegalovirus Infection in SOT Recipients and HSCT Patients
An observational study of Cytomegalovirus Infections, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 23 sites in 9 countries.
Trial summary
The ReCySOHT study is a multicenter, retrospective, observational case-control study on the risk factors for developing a ganciclovir-resistant/refractory (GCV-RR) cytomegalovirus infection in patients receiving solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytomegalovirus Infections
- How many people
- 100 participants
- Where
- 23 sitesin 9 countries
- Study dates
- 19 Jun 2023to 28 Feb 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All adult (≥ 18 years) patients who underwent SOT or HSCT developing CMV-infection treated with GC/VGC during the study period will be screened for inclusion according to inclusion and exclusion criteria. Eligible patients will be classified as cases or controls according to the following definitions: * Case: SOT or HSCT recipients with genotypically confirmed GCV-RR CMV-event; * Control: SOT or HSCT recipients with "presumed" GCV-S CMV-event on the basis of good microbiological and clinical response to standard GCV/VGC treatment.
Who may be able to join
- All adult (≥ 18 years) patients who underwent SOT or HSCT developing CMV-infection treated with GC/VGC
- Ability to understand the purpose of the study and provide signed and dated informed consent
Who cannot join
- Lack of clinical and/or laboratory data regarding the type of CMV event
- Lack of the serological mismatch at transplantation
- Lack of the type of SOT or HSCT
- Lack of the patient and graft outcome at 30, 60 or 90 days after CMV event diagnosis
Trial locations and contacts
23 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 9 countries
Italy10 sites, 10 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, Bologna, 40138
Renato Pascale, MD, +39 051 214 4350, renato.pascale@aosp.bo.it
- Not yet recruiting
Ospedale San Martino
Genova, 16132
Malgorzata Mikulska, m.mikulska@unige.it
- Recruiting
Policlinico di Milano
Milan, 20122
Alessandra Bandera, alessandra.bandera@policlinico.mi.it
- Recruiting
Azienda Ospedaliero-Universitaria di Modena
Modena, 41125
Erica Franceschini, ericafranceschini0901@gmail.com
- Not yet recruiting
Azienda Ospedaliera dei Colli
Naples, 80131
Emanuele Durante Mangoni, emanuele.durante@unicampania.it
- Not yet recruiting
Azienda Ospedale-Università Padova
Padova, 35128
Serena Marinello, serena.marinello@aopd.veneto.it
- Recruiting
Istituto mediterraneo per i trapianti e terapie ad alta specializzazione (ISMETT)
Palermo, Palermo, 90127
Alessandra Mularoni, MD, +390912192111, amularoni@ismett.edu
- Not yet recruiting
Humanitas Research Hospital
Rozzano, Milano, 20089
Bartoletti Michele, michele.bartoletti@hunimed.eu
- Recruiting
AOU Città della salute e della scienza
Torino, 10126
Silvia Corcione, silvia.corcione@unito.it
- Not yet recruiting
ASST dei Sette Laghi
Varese, 21100
Paolo Grossi, paolo.grossi@uninsubria.it
Spain4 sites, 4 recruiting
- Recruiting
Hospital Clinic
Barcelona, 08036
Maria Angeles Marcos, MMARCOS@clinic.cat
- Recruiting
Instituto Maimónides de Investigación Biomédica de Córdoba
Córdoba, 14004
Julián Torre-Cisneros, julian.torre.sspa@juntadeandalucia.es
- Not yet recruiting
Gregorio Marañón General University Hospital
Madrid, 28007
Patricia Munoz, pmunoz12345@icloud.com
- Not yet recruiting
University Hospital 12 de Octubre
Madrid, 28026
Jose M. Aguado, jaguadog1@gmail.com
Belgium2 sites, 2 recruiting
- Not yet recruiting
Institut Jules Bordet
Brussels, 1070
Angela Loizidou, angela.loizidou@bordet.be
- Not yet recruiting
University Hospitals Leuven
Leuven, 3000
Laurent Godinas, laurent.godinas@uzleuven.be
Switzerland2 sites, 2 recruiting
- Not yet recruiting
Centre hospitalier universitaire vaudois (CHUV)
Lausanne, Lausanne, 1011
Manuel Oriol, Oriol.Manuel@chuv.ch
- Not yet recruiting
University Hospital Zurich
Zurich, 8091
Nicolas Mueller, Nicolas.Mueller@usz.ch
United States1 site, 1 recruiting
- Not yet recruiting
MD Anderson Cancer Center
Houston, Texas, 77030-4009
Roy F. Chemaly, rfchemaly@mdanderson.org
Finland1 site, 1 recruiting
- Not yet recruiting
Helsinki University Central Hospital
Helsinki, Helsinki, 00290
llkka Helanterä, ilkka.helantera@helsinki.fi
France1 site, 1 recruiting
- Not yet recruiting
Centre Hospitalier Universitaire de Limoges
Limoges, Limoges, 87000
Sophie Alain, sophie.alain@unilim.fr
Portugal1 site, 1 recruiting
- Not yet recruiting
São João University Hospital
Porto, 4200-319
André Silva Pinto, andre.silva.pinto@chsj.min-saude.pt
United Kingdom1 site, 1 recruiting
- Not yet recruiting
Manchester University NHS Foundation Trust
Manchester
Karthik Santhanakrishnan, karthik.santhanakrishnan@mft.nhs.uk
About this study
Official title: Epidemiological Burden of and Risk Factors for Ganciclovir Resistant/Refractory Cytomegalovirus in Solid Organ Transplant and Hematopoietic Stem Cell Transplant Patients: Multicentre Cohort Study
The ReCySOHT study is a multicenter, retrospective, observational case-control study on the risk factors for developing a ganciclovir-resistant/refractory (GCV-RR) cytomegalovirus infection in patients receiving solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). Aims of the study are to investigate the incidence of and risk factors for GCV-RR CMV infection in SOT recipients and HSCT patients in order to design further studies aimed at preventing and improving the patient management of GCV-RR CMV infections.
Read the detailed description
Cytomegalovirus (CMV) is an important cause of morbidity and mortality in solid organ transplant (SOT) patients and hematopoietic stem cell transplant (HSCT) patients. Ganciclovir (GCV) is the first line therapy for treatment and prevention of CMV infection in SOT and HSCT recipients, with established efficacy and relatively safe profile.
Ganciclovir-resistant or refractory (GCV-RR) CMV is an uncommon but frightening clinical problem due to limited, toxic and less effective therapeutic alternative drugs. Indeed, some studies indicate that GCV-RR is associated with significant additional attributable morbidity and mortality in SOT and HSCT recipients compared with ganciclovir susceptible (GCV-S) CMV disease.
Few data are available about the incidence of GCV-RR-CMV in SOT and HSCT patients showing a range from 0% to 3% . The serological mismatch group and the type of SOT have been reported as the main factors influencing such range. Indeed, in one of the largest experience now available in SOT, the incidence of GCV-resistant (GCV-RT) CMV infection accounted up to 12% in a cohort of lung transplant recipients. Among HSCT patients, haploidentical, allogeneic unrelated, and cord blood HSCT have been associated with increased risk of GCV-RR CMV infection. Among risk factors for GCV-RR, high-risk D/R subset (R- in SOT and R+ in HSCT), high viral loads, inadequate drug delivery, increased durations of antiviral drug exposure and the use of more potent immunosuppressive regimens have been reported. However, these reports come from small, monocentric experiences with a limited number of cases, providing a fragmentary picture of the overall burden and epidemiological characteristics of GCV-RR in transplant patients. Information of the epidemiological background of GCV-RR after transplantation could be helpful in improving preventive management and reducing the emergence of GCV-RT episodes. Indeed, studies investigating viral genetic alterations showed that mutations conferring ganciclovir resistance are not present at baseline but emerge and become amplified over time, especially in the presence of an incompletely suppressive drug exposure. The GCV-RT is due to mutations in UL97 and UL54 genes. UL97 mutations confer various degrees of phenotypic resistance to ganciclovir. Mutations in UL54 determine higher-level resistance to ganciclovir and usually appear as a second step after mutations in UL97.
The investigators carry-out a multicenter retrospective observational study to define incidence of GCV-RR CMV-infection in SOT and HSCT patients and to identify the risk factors for its development in SOT and HSCT recipients. Data from this study could be useful to design further studies aimed at preventing and improving the patient management of GCV-RR CMV infections.
- Conditions
- Cytomegalovirus Infections
- Keywords
- Ganciclovir-resistant CMV, Cytomegalovirus, Solid Organ Transplant, Ganciclovir, Ganciclovir-refractory CMV, Hematopoietic Stem Cell Transplant
- Medical subject headings
- Cytomegalovirus Infections, Multiple Acyl Coenzyme A Dehydrogenase Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Solid Organ Transplant and Hematopoietic Stem Cell Transplant patients | Solid Organ Transplant (SOT) and Hematopoietic Stem Cell Transplant (HSCT) patients with Ganciclovir Resistant or Refractory Cytomegalovirus infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
To define incidence of GCV-RR CMV-infection in SOT and HSCT patients
To define incidence of GCV-RR CMV-infection in SOT and HSCT patients
Measured: Through study completion, an average of 1 year
To define the risk factors for GCV-RR CMV-infection development in SOT and HSCT patients
To define the risk factors for GCV-RR CMV-infection development in SOT and HSCT patients
Measured: Through study completion, an average of 1 year
Secondary outcomes (8)
To compare type of CMV episode between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare type of CMV episode: infection or disease (the last cathegorized as CMV syndrome or Tissue invasion) between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To compare virological cure between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare virological cure at 30, 60 and 90 days after CMV infection diagnosis and relapse of CMV infection between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To compare clinical cure between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare clinical cure at 30, 60 and 90 days after CMV infection diagnosis between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To compare graft outcome between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare graft failure rate and the need of re-transplant between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To compare the need of ICU and hospital stay between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare total length of ICU and hospital stay between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To compare the need of readmission in ICU and/or hospital between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare the need of readmission in ICU and/or hospital between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To compare all-cause mortality between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
To compare all-cause mortality during infection episode and follow-up (30, 60, 90 days after the first CMV infection diagnosis) between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Measured: Through study completion, an average of 1 year
To describe the therapeutic management of GCV-RR CMV-infection
To describe the therapeutic management of GCV-RR CMV-infection including the use of CMV-specific T-cell assay
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2022
- Study start19 Jun 2023
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytomegalovirus InfectionsStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Renato Pascale, MD, Principal investigator, IRCCS AOUBO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05234723
- Sponsor's protocol ID
- ReCySOHT
- Acronym
- ReCySOHT
- Status last verified
- Jun 2026
- First submitted
- 9 Jan 2022
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidemiological Burden of and Risk Factors for Ganciclovir Resistant/Refractory Cytomegalovirus in Solid Organ Transplant and Hematopoietic Stem Cell Transplant Patients: Multicentre Cohort Study
- ClinicalTrials.gov ID
- NCT05234723
- Acronym / sponsor ID
- ReCySOHT / ReCySOHT
- Conditions
- Cytomegalovirus Infections
- Keywords
- Ganciclovir-resistant CMV, Cytomegalovirus, Solid Organ Transplant, Ganciclovir, Ganciclovir-refractory CMV, Hematopoietic Stem Cell Transplant
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 19 Jun 2023 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 10 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The ReCySOHT study is a multicenter, retrospective, observational case-control study on the risk factors for developing a ganciclovir-resistant/refractory (GCV-RR) cytomegalovirus infection in patients receiving solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). Aims of the study are to investigate the incidence of and risk factors for GCV-RR CMV infection in SOT recipients and HSCT patients in order to design further studies aimed at preventing and improving the patient management of GCV-RR CMV infections.
Detailed description
Cytomegalovirus (CMV) is an important cause of morbidity and mortality in solid organ transplant (SOT) patients and hematopoietic stem cell transplant (HSCT) patients. Ganciclovir (GCV) is the first line therapy for treatment and prevention of CMV infection in SOT and HSCT recipients, with established efficacy and relatively safe profile.
Ganciclovir-resistant or refractory (GCV-RR) CMV is an uncommon but frightening clinical problem due to limited, toxic and less effective therapeutic alternative drugs. Indeed, some studies indicate that GCV-RR is associated with significant additional attributable morbidity and mortality in SOT and HSCT recipients compared with ganciclovir susceptible (GCV-S) CMV disease.
Few data are available about the incidence of GCV-RR-CMV in SOT and HSCT patients showing a range from 0% to 3% . The serological mismatch group and the type of SOT have been reported as the main factors influencing such range. Indeed, in one of the largest experience now available in SOT, the incidence of GCV-resistant (GCV-RT) CMV infection accounted up to 12% in a cohort of lung transplant recipients. Among HSCT patients, haploidentical, allogeneic unrelated, and cord blood HSCT have been associated with increased risk of GCV-RR CMV infection. Among risk factors for GCV-RR, high-risk D/R subset (R- in SOT and R+ in HSCT), high viral loads, inadequate drug delivery, increased durations of antiviral drug exposure and the use of more potent immunosuppressive regimens have been reported. However, these reports come from small, monocentric experiences with a limited number of cases, providing a fragmentary picture of the overall burden and epidemiological characteristics of GCV-RR in transplant patients. Information of the epidemiological background of GCV-RR after transplantation could be helpful in improving preventive management and reducing the emergence of GCV-RT episodes. Indeed, studies investigating viral genetic alterations showed that mutations conferring ganciclovir resistance are not present at baseline but emerge and become amplified over time, especially in the presence of an incompletely suppressive drug exposure. The GCV-RT is due to mutations in UL97 and UL54 genes. UL97 mutations confer various degrees of phenotypic resistance to ganciclovir. Mutations in UL54 determine higher-level resistance to ganciclovir and usually appear as a second step after mutations in UL97.
The investigators carry-out a multicenter retrospective observational study to define incidence of GCV-RR CMV-infection in SOT and HSCT patients and to identify the risk factors for its development in SOT and HSCT recipients. Data from this study could be useful to design further studies aimed at preventing and improving the patient management of GCV-RR CMV infections.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Solid Organ Transplant and Hematopoietic Stem Cell Transplant patients | – | –Solid Organ Transplant (SOT) and Hematopoietic Stem Cell Transplant (HSCT) patients with Ganciclovir Resistant or Refractory Cytomegalovirus infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All adult (≥ 18 years) patients who underwent SOT or HSCT developing CMV-infection treated with GC/VGC during the study period will be screened for inclusion according to inclusion and exclusion criteria. Eligible patients will be classified as cases or controls according to the following definitions: * Case: SOT or HSCT recipients with genotypically confirmed GCV-RR CMV-event; * Control: SOT or HSCT recipients with "presumed" GCV-S CMV-event on the basis of good microbiological and clinical response to standard GCV/VGC treatment.
Key inclusion criteria (2 listed)
- All adult (≥ 18 years) patients who underwent SOT or HSCT developing CMV-infection treated with GC/VGC
- Ability to understand the purpose of the study and provide signed and dated informed consent
Key exclusion criteria (4 listed)
- Lack of clinical and/or laboratory data regarding the type of CMV event
- Lack of the serological mismatch at transplantation
- Lack of the type of SOT or HSCT
- Lack of the patient and graft outcome at 30, 60 or 90 days after CMV event diagnosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To define incidence of GCV-RR CMV-infection in SOT and HSCT patients
Time frame: Through study completion, an average of 1 year
To define incidence of GCV-RR CMV-infection in SOT and HSCT patients
To define the risk factors for GCV-RR CMV-infection development in SOT and HSCT patients
Time frame: Through study completion, an average of 1 year
To define the risk factors for GCV-RR CMV-infection development in SOT and HSCT patients
8 secondary outcomes
To compare type of CMV episode between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To compare virological cure between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To compare clinical cure between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To compare graft outcome between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To compare the need of ICU and hospital stay between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To compare the need of readmission in ICU and/or hospital between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To compare all-cause mortality between SOT and HSCT patients with GCV-RR versus GCV-S CMV-infection
Time frame: Through study completion, an average of 1 year
To describe the therapeutic management of GCV-RR CMV-infection
Time frame: Through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Renato Pascale, MD principal investigator
IRCCS AOUBO
23 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytomegalovirus Infections, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 23 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Italy, Spain, Belgium, Switzerland, United States and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Renato Pascale, MD (+390512144350, renato.pascale@aosp.bo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To define incidence of GCV-RR CMV-infection in SOT and HSCT patients (time frame: Through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.