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Transplantation InfectionPhase 4EVERCMVNCT02328963

Proportion of CMV Seropositive Kidney Transplant Recipients Who Will Develop a CMV Infection When Treated With an Immunosuppressive Regimen Including Everolimus and Reduced Dose of Cyclosporine Versus an Immunosuppressive Regimen With Mycophenolic Acid and Standard Dose of Cyclosporine A

A Phase 4 study testing Everolimus and mycophenolic acid in people with Transplantation Infection and Cytomegalovirus Infection, run by University Hospital, Bordeaux at 9 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Cytomegalovirus (CMV) infection is the most frequent opportunistic viral infection after transplantation. It is associated with an increased incidence of acute rejection and lower graft and patient survivals. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Everolimus and mycophenolic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
186 participants
Where
9 sitesFrance
Study dates
2 May 2014to 10 Oct 2018
Phase
Phase 4
Are there results?
None posted in the registry

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

Who may be able to join

  • Age ≥ 18 years.
  • End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation.
  • Patient seropositive for CMV (confirmed within two weeks post-transplant) and having received an allograft from a CMV seropositive or seronegative donor.
  • Receiving a kidney transplant from a deceased or living donor with compatible ABO blood type.
  • Female subject of childbearing potential must have a negative serum pregnancy test at enrollment and must agree to maintain effective birth control during the study and two months later the discontinuation of the test drug.
  • Total ischemia time below 36 hours.
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  • Capable of understanding the purpose and risks of the study.
  • Fully informed and having given written informed consent (signed Informed Consent has been obtained).
  • Affiliation to the social security regimen

Who cannot join

  • CMV seronegative patient.
  • Historical or current TGI (French equivalence of calculated PRA) > 85 %
  • Presence of historical or current anti-HLA donor specific antibodies
  • Patient who received anti-CMV therapy within the past 30 days prior to screening.
  • Receiving or having previously received an organ transplant other than a kidney.
  • Receiving a graft from a non-heart-beating donor.
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  • Patient known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B (HBV; HBs Ag positive) or Hepatitis C (HCV; anti-HCV Ab positive).elevated SGPT/ALT and/or SGOT/AST and/or total bilirubin levels ≥ 2 times the upper value of the normal range of the investigational site or receiving a graft from a hepatitis C or B positive donor.
  • Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer.
  • Known allergy or intolerance to everolimus, valganciclovir, ganciclovir, mycophenolic acid, basiliximab, corticosteroids, or cyclosporine A or any of the product excipients.
  • Severe hyperlipidemia defined by: total cholestérol ≥ 9,1 mmol/L (≥ 350 mg/dL) et/ou triglycérides ≥ 8,5 mmol/l (≥ 750 mg/dL) in spite an adequate medication.
  • Patient has adequate hematological post-transplant defined as:
  • Absolute neutrophil count (ANC) > 1000 cells/μL.
  • Platelet count > 50,000 cells/μL.
  • Hemoglobin > 8.0 g/dL.
  • Requiring initial therapy with induction immunosuppressive antibody preparations, such as anti-thymocyte globulins or rituximab or IVIG.
  • Currently participating in another clinical trial investigating drugs. Observational studies are not considered as an exclusion criteria
  • Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator.
  • Unlikely to comply with the visits scheduled in the protocol.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

France9 sites
  • CHU de Bordeaux

    Bordeaux, 33000

  • CHU La Cavale Blanche

    Brest, 29609

  • CHRU Caen - Hôpital de Caen

    Caen, 14033

  • CHU de Limoges - Hôpital Dupuytren

    Limoges

  • Hôpital Edouard Herriot

    Lyon, 69003

  • APHP - Hôpital Necker

    Paris, 75015

  • APHP - Kremlin Bicetre

    Paris, 94275

  • CHRU Strasbourg

    Strasbourg

  • CHU de Toulouse - Hôpital Rangueil

    Toulouse, 31000

Other trials in France

About this study

Official title: A Multicenter, Two Arms, Randomized, Open Label Clinical Phase IV Study Investigating the Proportion of CMV Seropositive Kidney Transplant Recipients Who Will Develop a CMV Infection Within the First 6 Months Post-transplantation When Treated With an Immunosuppressive Regimen Including Everolimus (Certican®) and Reduced Dose of Cyclosporine A (Neoral®) Versus an Immunosuppressive Regimen With Mycophenolic Acid (Myfortic®) and Standard Dose of Cyclosporine A (Neoral®).

Cytomegalovirus (CMV) infection is the most frequent opportunistic viral infection after transplantation. It is associated with an increased incidence of acute rejection and lower graft and patient survivals. The goal of this study is to demonstrate that an immunosuppressive regimen associating everolimus and reduced dose of cyclosporine A can prevent acute rejection episodes as efficiently as standard regimen but also efficiently reduce the incidence of CMV infection at 6 months post-transplantation.

Read the detailed description

Cytomegalovirus (CMV) infection is the most frequent opportunistic viral infection after kidney transplantation. Therefore most of the patients receive an universal prophylaxis. On the contrary to CMV naïve patients, seropositive recipients (R+) have already mounted a specific immunologic response directed against the virus, which is not completely abrogated by immunosuppressive drugs. Although CMV infection management guidelines offer little guidance on immunosuppressive therapy for preventing CMV infection and disease, recent data plead for reappraising the place of mTOR inhibitors in this situation. The potential anti-CMV action of these molecules could be added to their potential antitumor effect and their equivalent immunosuppressive efficacy in kidney transplant recipients at low immunological risk. By the way, it could represent an alternative of a systematic universal prophylaxis in R+ kidney transplant recipients. However, the proof of this anti-CMV action must be confirmed in vivo in a study, which could have a close monitoring of CMV infection.

We therefore designed a prospective multicentric randomized controlled trial comparing an immunosuppressive regimen based on everolimus and reduced dose of cyclosporine A to a regimen based on mycophenolic acid and standard dose of cyclosporine A, in order to demonstrate the superiority of the first one in the prevention of CMV infection.

Subjects will be randomized to one of the two treatment arms and will be followed for a period of 12 months. Whole blood CMV real time PCR will be performed every week during the first three months, then every two weeks from Month 3 to Month 6, then at Months 8, 10 and 12. Incidence of CMV infection will be compared between the two arms at 6 and 12 months post-transplantation.

Being tested
Everolimus, mycophenolic acid
Keywords
Cytomegalovirus infection and disease, CMV-seropositive recipients, Everolimus, preemptive strategy, mTOR inhibitor
Medical subject headings
Cytomegalovirus Infections, Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Everolimus : 0.75 bid, targeted to 3-8 ng/ml

    Cyclosporin A :

    CsA target ranges for Arm 1 will be 100-200 ng/mL from Day 3 to Month 2, decreasing to 75-150 ng/mL from Month 2 to Month 4 and 25-50 ng/mL from Months 6 to 12.

    Corticosteroids :

    Méthylprednisolone: 500 mg at Day 0, 120 mg à Day 1. Prednisone or equivalent: 20 mg/d from Day 3. Corticosteroid dosing will be tapered according to center standard practice but to not less than 5 mg per day for the duration of the 12-month study

    Basiliximab :Day 0: 20 mg ; Day 4: 20 mg

  • mycophenolic acidDrug

    Mycophenolic acid :

    1080 mg bid for one month, then 720 mg bid

    Cyclosporin A :

    CsA target ranges for Arm 1 will be 100-200 ng/mL from Day 3 to Month 2, decreasing to 75-150 ng/mL from Month 2 to Month 4 and 25-50 ng/mL from Months 6 to 12.

    Corticosteroids :

    Méthylprednisolone: 500 mg at Day 0, 120 mg à Day 1. Prednisone or equivalent: 20 mg/d from Day 3. Corticosteroid dosing will be tapered according to center standard practice but to not less than 5 mg per day for the duration of the 12-month study

    Basiliximab :Day 0: 20 mg ; Day 4: 20 mg

Study groups in NCT02328963
Study groupRoleWhat they receive
EverolimusExperimentalEverolimus + reduced dose of cyclosporine A
Receives: Drug: Everolimus
mycophenolic acidActive comparatormycophenolic acid + standard dose of cyclosporin A
Receives: Drug: mycophenolic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants without CMV infection and without graft loss in CMV seropositive kidney transplant recipients.

    The primary objective of this study is to compare the survival without CMV infection and without graft loss in CMV seropositive kidney transplant recipients, within the first 6 months post-transplantation when treated with an immunosuppressive regimen including everolimus (Certican®) and reduced dose (RD) of cyclosporine A (Néoral®) versus an immunosuppressive regimen with mycophenolic acid (Myfortic®) and standard dose (SD) of cyclosporine A (Néoral®).

    Measured: 6 months post-transplantation

Secondary outcomes (23)
  1. Proportion of patients who will develop CMV disease

    The proportion of patients who will develop CMV disease during the first 6 and 12 months post-transplantation (CMV disease includes both CMV syndrome and CMV tissue-invasive disease).

    Measured: 6 and 12 months post-transplantation

  2. Proportion of patient with graft loss, death and loss of follow-up

    Measured: 12 months post-transplantation

  3. Proportion of patient with acute rejection, graft loss, death and loss of follow-u

    Measured: 12 months

  4. Level to the first CMV DNAemia

    Measured: Throughout the study

  5. Time to the first CMV disease

    Measured: Throughout the study

  6. Proportion of patients treated for CMV infection in both groups

    Measured: 6 months

  7. Half-life of decreasing of DNAemia

    Measured: after initiation of anti-CMV therapy

  8. Occurrence of treatment failure, defined as the absence of viral eradication.

    Measured: Day 49 (or 8 weeks) after the initiation of anti-CMV therapy

  9. Occurrence of CMV mutation (UL97 ou UL54) associated with a resistance to an anti-CMV therapy.

    Measured: Throughout the study

  10. Graft function

    Graft function defined as glomerular filtration rate (GFR) estimated by simplified MDRD formula and proteinuria/creatininuria ratio.

    Measured: 6 and 12 months post-transplantation

  11. Proportion of patients with biopsy-proven acute rejection (BPAR)

    Measured: 6 and 12 months post-transplantation

  12. Degree of interstitial fibrosis/tubular atrophy

    Measured: 12 months on protocol biopsies

  13. Graft and patient survival

    Measured: 6 and 12 months post-transplantation

  14. Proportion of BK virus viremia

    Measured: month 1, 3, 6 and 12

  15. Proportion of patients with adverse events (AE) and/or serious adverse events (SAE) including opportunistic infections and neoplasias.

    Measured: 12 months

  16. Proportion of patients with haematological disorders

    The proportion of patients with haematological disorders (neutropenia, anaemia, thrombopenia)

    Measured: 12 months

  17. Proportion of patients with diarrhea

    Measured: 12 months

  18. Proportion of dyslipidemia

    Measured: 12 months

  19. Proportion of patients with occurrence of New Onset Diabetes Mellitus as defined by American Diabetic Association (ADA) criteria.

    Measured: 12 months

  20. Proportion of patients who will discontinue the immunosuppressive treatment and the reasons why.

    Measured: 12 months

  21. Proportion of patients with delayed graft function

    Measured: 12 months

  22. Proportion of lymphocele

    Measured: 12 months

  23. Time to the first CMV DNAemia

    Measured: Throughout the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2014 (estimated)
  2. Study start2 May 2014
  3. Primary completion10 Oct 2018
  4. Study completion10 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
186 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02328963
Sponsor's protocol ID
CHUBX2012/29
Acronym
EVERCMV
Status last verified
Nov 2018
First submitted
1 Sep 2014
Last updated
27 Jul 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 34725108
  • 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.

    PubMed 34990047

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Everolimus and mycophenolic acid in people with Transplantation Infection and Cytomegalovirus Infection, run by University Hospital, Bordeaux at 9 sites in France.

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 9 inclusion and 18 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: finished, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants without CMV infection and without graft loss in CMV seropositive kidney transplant recipients. (time frame: 6 months post-transplantation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02328963, which also lists 2 linked publications.

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 27 Jul 2026.

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