Clinical trial NCT05701228: Casting Light on HOst-cytomegaloviRUs Interaction in Solid Organ Transplantation
Official title: Casting Light on HOst-cytomegaloviRUs Interaction in Solid Organ Transplantation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cytomegalovirus Infections
Solid Organ Transplantation
Keywords: immunocompromised hosts
immune response
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2023-01-27
Enrollment: 525
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohort 1 will include 450 patients at the time of transplantation:

Kidney: 6 groups : 50 R+ATG no mTORi, 30 R+ATG mTORi, 50 R+ no ATG no mTORi, 30 R+ no ATG mTORi, 50 D+R- no mTORi, 30 D+R- mTORi Lung: 3 groups of 20 patients R+ ATG,R+ no ATG, D+R- Heart: 3 groups of 30 patients R+ ATG, R+ no ATG, D+R- Liver: 3 groups of 20 patients R+ ATG, R+ no ATG, D+R-

Cohort 2 will include 150 patients at the time of the infection:

Approximatively 75 patients are expected to roll-over from the cohort of solid-organ transplant recipients included at day 0 of transplantation (cohort 1).

Additional 75 patients developing a CMV infection will be also included.

Brief summary: CMV disease remains the most frequent infectious complication post-transplant and it is associated to high morbidity and even mortality. Global efforts from both transplant physicians and researchers in the field is needed to better characterize the host-virus interactions in the transplant setting, with the aim of decreasing the burden of disease and improve the well-being of patients.

"HORUS" (Casting light on HOst-cytomegaloviRUs interaction in Solid organ transplantation) study is a European research project, funded by the European Commission (Horizon Europe) involving 16 partners in seven European countries (France, Spain, Czech Republic, Belgium, Switzerland, Germany and Italy) aiming to better characterize the host-CMV interactions in SOT recipients. The first aim of HORUS study will be to build a European cohort of SOT recipients including clinical characterization and the constitution of a biocollection, which is the aim of HORUS cohort, in order to perform biological, immunological, gene expression, viral kinetics and deep viral genome characterization in the global European HORUS project to improve our understanding of the development of a CMV immune response in the context of immunosuppression.

Detailed description: The overall goal of HORUS study is to improve our understanding of the host-virus relationship of Cytomegalovirus within immunocompromised solid organ transplant recipients in order to propose both knowledge improvement, and clinical immune signatures for decreasing CMV infections/diseases incidence and avoiding the use of toxic antiviral therapy. HORUS' general goal is to enhance our knowledge on risk factors, disease progression and clinical outcomes by analyzing together immune host characteristics, viral characteristics and immunosuppressive drugs. The constitution of two clinical cohorts ("The day 0 of graft cohort" and "the day 0 of infection cohort") will constitute the aim of "HORUS study" with clinical data collection and biocollection which will be used in the global HORUS project to identify immune profiles of patients integrating all the actors involved in viral control, viral and clinical parameters associated with a higher risk of CMV replication and an evolution toward a CMV difficult-to-treat disease.

"HORUS cohorts" is a project of biological samples biobank from solid organ transplant recipients in Hospitals : France (Bordeaux, Toulouse, Paris, Lyon), Spain (Barcelona), Tchequie (Karlova), Italy (Bologna), Switzerland (Lausanne).

Its main objective of this protocol is to collect, prepare, and store

* under CRB conditions (NFS96900) longitudinal biological samples from solid organ transplants (heart, kidney, lung, liver), from day 0 of transplantation and followed for the occurrence of CMV infection.
* Clinical and sociodemographic data associated with this longitudinal biocollection

The secondary objective is to support for the global "HORUS" project aiming at:

* Studying the longitudinal clinical, viral and immunological profile of solid organ transplants after transplantation with or without CMV disease and if CMV disease with or without a "difficult-to-treat" (CMV persistence, relapse, antiviral drug resistance)
* Defining signatures combining virological data, clinical data, donor/recipient data and immune profile of CMV-specific immunity to identify :i) patients at risk of developing CMV infection and ii) at day 0 of infection to identify patient at risk of developing difficult-to-treat CMV infection. The collection of biological samples, associated with the clinico-biological data, to find the global signature constitutes an indispensable step.

Eligibility criteria: A cohort 1 of solid-organ transplant recipients at day 0 of transplantation will be included:

* Consecutive patients meeting the following inclusion criteria will be included:

  * Men and women,
  * Age \>= 18 years receiving a (living or deceased donor) kidney, lung, liver, and heart allograft,
  * written informed consent obtained from subject,
  * ability to understand and give their written consent,
  * affiliated to health insurance.
* Exclusion criteria would be:

  * D-R- recipients,
  * participant unable or unwilling to comply with study procedures,
  * subjects who are legally detained in an official institution.

A cohort 2 of solid-organ transplant recipients at day 0 of infection:

* Consecutive patients meeting the following inclusion criteria will be included:

  * Men and women,
  * Age \>= 18 years receiving a (living or deceased donor) kidney, lung, liver, and heart allograft
  * written informed consent obtained from subject,
  * ability to understand and give their written consent,
  * affiliated to health insurance,
  * post-transplant CMV infection episode.
* Exclusion criteria would be:

  * D-R- recipients,
  * participant unable or unwilling to comply with study procedures,
  * subjects who are legally detained in an official institution.

Primary outcomes:
measure: Biobank inventory for cohort 1 : day 0 of transplantation
timeFrame: from day of graft (inclusion day) to month 24
measure: Biobank inventory for cohort 1 : day 0 of transplantation
timeFrame: from day of graft (inclusion day) to month 24
measure: Biobank inventory for cohort 1 : day 0 of transplantation
timeFrame: from day of graft (inclusion day) to month 24
measure: Biobank inventory for cohort 1 : day 0 of transplantation
timeFrame: from day of graft (inclusion day) to month 24
measure: Biobank inventory for cohort 1 : day 0 of transplantation
timeFrame: from day of graft (inclusion day) to month 24
measure: Biobank inventory for cohort 2 : day 0 of infection
timeFrame: from day of infection (inclusion day) to month 12
measure: Biobank inventory for cohort 2 : day 0 of infection
timeFrame: from day of infection (inclusion day) to month 12
measure: Biobank inventory for cohort 2 : day 0 of infection
timeFrame: from day of infection (inclusion day) to month 12
measure: Biobank inventory for cohort 2 : day 0 of infection
timeFrame: from day of infection (inclusion day) to month 12
measure: Biobank inventory for cohort 2 : day 0 of infection
timeFrame: from day of infection (inclusion day) to month 12
measure: Biobank inventory for cohort 2 : day 0 of infection
timeFrame: from day of infection (inclusion day) to month 12
measure: Creation of a Clinical Database
timeFrame: From inclusion day to month 36
Secondary outcomes:
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: Caracterised the solid organ transplants after transplantation
timeFrame: From inclusion day to month 36
measure: CMV caracterisation
timeFrame: From inclusion day to month 36
measure: CMV caracterisation
timeFrame: From inclusion day to month 36
measure: CMV caracterisation
timeFrame: From inclusion day to month 36
measure: CMV caracterisation
timeFrame: From inclusion day to month 36
measure: CMV infection caracterisation
timeFrame: From day of infection (inclusion day) to month 36
measure: CMV infection caracterisation
timeFrame: From day of infection (inclusion day) to month 36
measure: CMV infection caracterisation
timeFrame: From day of infection (inclusion day) to month 36
measure: CMV infection caracterisation
timeFrame: From day of infection (inclusion day) to month 36
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hopitel Pellegrin
city: Lyon
country: France
facility: Hôpital Edouard Hériot
city: Paris
country: France
facility: Hôpital LA PITIE SALPETRIERE
city: Paris
country: France
facility: Hôpital Necker
city: Suresnes
country: France
facility: Hôpital Foch
city: Toulouse
country: France
facility: Hôpital Rangueil
city: Villejuif
country: France
facility: Hôpital Paul Brousse
Study officials:
affiliation: Clinical Epidemiology Unit at Bordeaux University Hospital
name: Laura RICHERT, Pr
role: STUDY_CHAIR
References: