NCT07570433

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.

Trial Health

67
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_4

Timeline
22mo left

Started Apr 2026

Geographic Reach
3 countries

4 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress5%
Apr 2026Mar 2028

Study Start

First participant enrolled

April 1, 2026

Completed
22 days until next milestone

First Submitted

Initial submission to the registry

April 23, 2026

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 6, 2026

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2028

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2028

Last Updated

May 6, 2026

Status Verified

April 1, 2026

Enrollment Period

1.8 years

First QC Date

April 23, 2026

Last Update Submit

April 29, 2026

Conditions

CMV Infection

Keywords

solid organ transplantationCMVcytomegalovirusimmunosuppressioneverolimusmTORiMPAinfectionimmune signature

Outcome Measures

Primary Outcomes (1)

  • Viral load decay

    Differences in log CMV viral load in plasma between baseline and 3 weeks

    3 weeks

Secondary Outcomes (2)

  • Change in CMV-specific immune signature score

    from enrollment to 3 and 8 weeks

  • Viral load decay according to immune signature

    3 and 8 weeks

Other Outcomes (6)

  • Viral load decay

    8 weeks

  • Viral load eradication

    3 and 8 weeks

  • Refractory CMV infection

    8 weeks

  • +3 more other outcomes

Study Arms (3)

50% reduction in the dose of MPA for a duration of minimum 21 days

EXPERIMENTAL

with standard antiviral therapy

Drug: 50% reduction in the dose of MPA

switch of MPA to everolimus with adapted dose of tacrolimus, for a duration of at least 56 days

EXPERIMENTAL

with standard antiviral therapy

Drug: Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus

Standard antiviral therapy without modulation of immunosuppression

ACTIVE COMPARATOR
Drug: standard antiviral therapy along with maintenance of their initial immunosuppressive therapy.

Interventions

50% reduction in the dose of MPADRUG

50% reduction in the dose of MPA with standard antiviral therapy

Also known as: Mycophenolic acid, Mycophenolate mofetil
50% reduction in the dose of MPA for a duration of minimum 21 days
standard antiviral therapy along with maintenance of their initial immunosuppressive therapy.DRUG

standard antiviral therapy along with maintenance of their initial immunosuppressive therapy (control group)

Also known as: control group
Standard antiviral therapy without modulation of immunosuppression
Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimusDRUG

Switch from MPA to a mammalian target of rapamycin inhibitor (mTORi), together with an adapted dose of tacrolimus, with standard antiviral therapy

Also known as: everolimus
switch of MPA to everolimus with adapted dose of tacrolimus, for a duration of at least 56 days

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • Patient not affiliated to the French social security system
  • Patient under legal protection (guardianship, curatorship).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Centre hospitalier universitaire Bordeaux (CHU Bordeaux)

Bourdeaux, Talence Cedex, 33404, France

Location

Centre hospitalier universitaire Toulouse (CHU Toulouse)

Toulouse, Toulouse, 31059, France

Location

Hospital Universitari Vall D'Hebron

Barcelona, Catalonia, 08035, Spain

Location

Centre hospitalier universitaire vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (12)

  • Qazi Y, Shaffer D, Kaplan B, Kim DY, Luan FL, Peddi VR, Shihab F, Tomlanovich S, Yilmaz S, McCague K, Patel D, Mulgaonkar S. Efficacy and Safety of Everolimus Plus Low-Dose Tacrolimus Versus Mycophenolate Mofetil Plus Standard-Dose Tacrolimus in De Novo Renal Transplant Recipients: 12-Month Data. Am J Transplant. 2017 May;17(5):1358-1369. doi: 10.1111/ajt.14090. Epub 2017 Jan 4.

    PMID: 27775865BACKGROUND

  • Viana LA, Cristelli MP, Basso G, Santos DW, Dantas MTC, Dreige YC, Requiao Moura LR, Nakamura MR, Medina-Pestana J, Tedesco-Silva H. Conversion to mTOR Inhibitor to Reduce the Incidence of Cytomegalovirus Recurrence in Kidney Transplant Recipients Receiving Preemptive Treatment: A Prospective, Randomized Trial. Transplantation. 2023 Aug 1;107(8):1835-1845. doi: 10.1097/TP.0000000000004559. Epub 2023 Jul 20.

    PMID: 37046380BACKGROUND

  • Kaminski H, Kamar N, Thaunat O, Bouvier N, Caillard S, Garrigue I, Anglicheau D, Rerolle JP, Le Meur Y, Durrbach A, Bachelet T, Savel H, Coueron R, Visentin J, Del Bello A, Pellegrin I, Dechanet-Merville J, Merville P, Thiebaut R, Couzi L. Incidence of cytomegalovirus infection in seropositive kidney transplant recipients treated with everolimus: A randomized, open-label, multicenter phase 4 trial. Am J Transplant. 2022 May;22(5):1430-1441. doi: 10.1111/ajt.16946. Epub 2022 Jan 19.

    PMID: 34990047BACKGROUND

  • Kaminski H, Marseres G, Yared N, Nokin MJ, Pitard V, Zouine A, Garrigue I, Loizon S, Capone M, Gauthereau X, Mamani-Matsuda M, Coueron R, Duran RV, Pinson B, Pellegrin I, Thiebaut R, Couzi L, Merville P, Dechanet-Merville J. mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional alphabeta and gammadelta T cells in Kidney Transplantation. J Am Soc Nephrol. 2022 Jan;33(1):121-137. doi: 10.1681/ASN.2020121753. Epub 2021 Nov 1.

    PMID: 34725108BACKGROUND

  • Poglitsch M, Weichhart T, Hecking M, Werzowa J, Katholnig K, Antlanger M, Krmpotic A, Jonjic S, Horl WH, Zlabinger GJ, Puchhammer E, Saemann MD. CMV late phase-induced mTOR activation is essential for efficient virus replication in polarized human macrophages. Am J Transplant. 2012 Jun;12(6):1458-68. doi: 10.1111/j.1600-6143.2012.04002.x. Epub 2012 Mar 5.

    PMID: 22390651BACKGROUND

  • Clippinger AJ, Maguire TG, Alwine JC. The changing role of mTOR kinase in the maintenance of protein synthesis during human cytomegalovirus infection. J Virol. 2011 Apr;85(8):3930-9. doi: 10.1128/JVI.01913-10. Epub 2011 Feb 9.

    PMID: 21307192BACKGROUND

  • Asberg A, Jardine AG, Bignamini AA, Rollag H, Pescovitz MD, Gahlemann CC, Humar A, Hartmann A; VICTOR Study Group. Effects of the intensity of immunosuppressive therapy on outcome of treatment for CMV disease in organ transplant recipients. Am J Transplant. 2010 Aug;10(8):1881-8. doi: 10.1111/j.1600-6143.2010.03114.x. Epub 2010 May 10.

    PMID: 20486914BACKGROUND

  • Dubrawka CA, Progar KJ, January SE, Hagopian JC, Nesselhauf NM, Malone AF. Impact of antimetabolite discontinuation following cytomegalovirus or BK polyoma virus infection in kidney transplant recipients. Transpl Infect Dis. 2022 Dec;24(6):e13931. doi: 10.1111/tid.13931. Epub 2022 Aug 26.

    PMID: 35980197BACKGROUND

  • Kaminski H, Garrigue I, Couzi L, Taton B, Bachelet T, Moreau JF, Dechanet-Merville J, Thiebaut R, Merville P. Surveillance of gammadelta T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants. J Am Soc Nephrol. 2016 Feb;27(2):637-45. doi: 10.1681/ASN.2014100985. Epub 2015 Jun 8.

    PMID: 26054538BACKGROUND

  • Bestard O, Kaminski H, Couzi L, Fernandez-Ruiz M, Manuel O. Cytomegalovirus Cell-Mediated Immunity: Ready for Routine Use? Transpl Int. 2023 Nov 7;36:11963. doi: 10.3389/ti.2023.11963. eCollection 2023.

    PMID: 38020746BACKGROUND

  • Kotton CN, Kumar D, Manuel O, Chou S, Hayden RT, Danziger-Isakov L, Asberg A, Tedesco-Silva H, Humar A; Transplantation Society International CMV Consensus Group. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025 Jul 1;109(7):1066-1110. doi: 10.1097/TP.0000000000005374. Epub 2025 Apr 9. No abstract available.

    PMID: 40200403BACKGROUND

  • Manuel O, Kralidis G, Mueller NJ, Hirsch HH, Garzoni C, van Delden C, Berger C, Boggian K, Cusini A, Koller MT, Weisser M, Pascual M, Meylan PR; Swiss Transplant Cohort Study. Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2013 Sep;13(9):2402-10. doi: 10.1111/ajt.12388. Epub 2013 Aug 5.

    PMID: 23914796BACKGROUND

Related Links

MeSH Terms

Conditions

Cytomegalovirus InfectionsInfections

Interventions

Mycophenolic AcidEverolimusControl Groups

Condition Hierarchy (Ancestors)

Herpesviridae InfectionsDNA Virus InfectionsVirus Diseases

Intervention Hierarchy (Ancestors)

CaproatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty AcidsLipidsSirolimusMacrolidesLactonesEpidemiologic Research DesignEpidemiologic MethodsInvestigative TechniquesResearch DesignMethods

Study Officials

  • Oriol Manuel, Professor, MD

    Service des maladies infectieuses, Centre hospitalier universitaire vaudois (CHUV)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Oriol Manuel, Professor, MD

CONTACT

+41 79 556 61 36oriol.manuel@chuv.ch

Elisa Ruiz-Arabi, MD, PhD

CONTACT

+41 79 556 5484elisa.ruiz-arabi@chuv.ch

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized open-label, phase IV non-comparative trial with three parallel arms
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associated Professor

Study Record Dates

First Submitted

April 23, 2026

First Posted

May 6, 2026

Study Start

April 1, 2026

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

March 1, 2028

Last Updated

May 6, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

After the study is completed, de-identified individual participant data may be shared. Data will be made available only after a formal request to the Principal Investigator (PI) and approval by the study's Scientific Committee. Data sharing will be limited to use for scientific research purposes and will follow all applicable privacy and ethical regulations.

Shared Documents
STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE

Locations

CH(1)ES(1)FR(2)