CMV Infection
Conditions
Keywords
solid organ transplantation, CMV, cytomegalovirus, immunosuppression, everolimus, mTORi, MPA, infection, immune signature
Brief summary
Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following organ transplantation. Cell-mediated immunity plays a crucial role in controlling CMV replication after transplantation. Immune monitoring involves the use of immune biomarkers to dynamically estimate the risk of CMV replication. This approach allows for the individualization of preventive and therapeutic strategies, improving patient outcomes. The HORUS-COPE trial is designed to assess the effect of immune modulation on CMV replication kinetics and to explore the performance of a selected immune signature during antiviral therapy for CMV infection to stratify patients based on their risk of not responding to immune modulation.
Detailed description
Cytomegalovirus (CMV) remains a significant cause of morbidity and mortality following organ transplantation. Cell-mediated immunity plays a crucial role in controlling CMV replication after transplantation. Immune monitoring involves the use of immune biomarkers-primarily those assessing cell-mediated immunity-to dynamically estimate the risk of CMV replication. This approach allows for the individualization of preventive and therapeutic strategies, improving patient outcomes. The HORUS consortium is a comprehensive European research initiative aimed at providing an in-depth assessment of immune signatures associated with CMV immune control in SOT recipients. One of the ultimate goals of the HORUS project is to leverage these immune signatures to design and implement a clinical trial evaluating their feasibility and impact in routine clinical practice. As part of this initiative, we introduce the HORUS-COPE trial, designed to assess the effect of immune modulation on CMV replication kinetics and to explore the performance of a selected immune signature during antiviral therapy for CMV infection to stratify patients based on their risk of not responding to immune modulation. Specifically, immune modulation consists of either: 1. a 50% dose reduction of an antimetabolite agent- mycophenolate mofetil \[MMF, Cellcept®\] or enteric-coated mycophenolate sodium \[EC-MPS, Myfortic®\]; hereafter referred to as mycophenolic acid \[MPA\]) 2. a switch from MPA to a mammalian target of rapamycin inhibitor (mTORi) everolimus, together with an adapted dose of tacrolimus.
Interventions
DRUG50% reduction in the dose of MPA
50% reduction in the dose of MPA with standard antiviral therapy
DRUGSwitch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus
Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus, with standard antiviral therapy
DRUGstandard antiviral therapy along with maintenance of their initial immunosuppressive therapy.
standard antiviral therapy along with maintenance of their initial immunosuppressive therapy (control group)
Sponsors
Oriol Manuel
Centre Hospitalier Universitaire Bordeaux
Centre Hospitalier Universitaire de Toulouse, FRANCE
Hospital Vall d'Hebron
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized open-label, phase IV non-comparative trial with three parallel arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinically stable adult patients (aged 18 years or older) who have received a solid organ transplant (e.g., kidney, liver, heart, lung, pancreas) and developed clinically significant CMV infection as determined by positive CMV PCR. * On maintenance therapy of tacrolimus, MPA, +/- steroids. * Informed consent signed.
Exclusion criteria
* Active acute graft rejection or significant graft dysfunction requiring modification of the current immunosuppressive regimen, in the opinion of the investigator. * Receipt of more than 72 hours of antiviral therapy for CMV infection prior to enrolment, before randomization, including valganciclovir and/or IV ganciclovir therapy * Known intolerance or hypersensitivity to mTOR inhibitors or to any component of the everolimus formulation. * Any medical condition that constitutes a contraindication to everolimus use, as judged by the investigator. * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Viral load decay | 3 weeks | Differences in log CMV viral load in plasma between baseline and 3 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CMV-specific immune signature score | from enrollment to 3 and 8 weeks | Change in the CMV-specific immune signature from baseline to week 3 and week 8, assessed using a predefined composite immune monitoring panel derived from the HORUS cohort. The panel will include CMV-specific T-cell functional assays and phenotyping, such as quantitative and qualitative measures of CD4 and CD8 CMV-specific responses, cytokine production, and selected activation/exhaustion markers. Results will be summarized as change from baseline at each time point. |
| Viral load decay according to immune signature | 3 and 8 weeks | Difference in log CMV viral load decay between baseline and 3 and 8 weeks according to baseline immune signature |
Countries
France, Spain, Switzerland
Contacts
CONTACTOriol Manuel, Professor, MD
CONTACTElisa Ruiz-Arabi, MD, PhD
PRINCIPAL_INVESTIGATOROriol Manuel, Professor, MD
Service des maladies infectieuses, Centre hospitalier universitaire vaudois (CHUV)
Outcome results
None listed