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

NCT02328963 | Completed Phase 4 DMC

• 1 other identifier: CHUBX2012/29
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 9

Brief 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. 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.

Conditions

Transplantation Infection; Cytomegalovirus Infection

Keywords

Cytomegalovirus infection and disease; CMV-seropositive recipients; Everolimus; preemptive strategy; mTOR inhibitor

Outcome Measures

Primary Outcomes (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®).

  6 months post-transplantation

Secondary Outcomes (23)

• Proportion of patients who will develop CMV disease

  6 and 12 months post-transplantation

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

  12 months post-transplantation

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

  12 months

• Level to the first CMV DNAemia

  Throughout the study

• Time to the first CMV disease

  Throughout the study

Study Arms (2)

Everolimus

EXPERIMENTAL

Everolimus + reduced dose of cyclosporine A

Drug: Everolimus

mycophenolic acid

ACTIVE COMPARATOR

mycophenolic acid + standard dose of cyclosporin A

Drug: mycophenolic acid

Interventions

Everolimus DRUG

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

Everolimus

mycophenolic acid DRUG

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

mycophenolic acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Novartis: collaborator

Study Sites (9)

CHU de Bordeaux

Bordeaux, 33000, France

Location

CHU La Cavale Blanche

Brest, 29609, France

Location

CHRU Caen - Hôpital de Caen

Caen, 14033, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, France

Location

Hôpital Edouard Herriot

Lyon, 69003, France

Location

APHP - Hôpital Necker

Paris, 75015, France

Location

APHP - Kremlin Bicetre

Paris, 94275, France

Location

CHRU Strasbourg

Strasbourg, France

Location

CHU de Toulouse - Hôpital Rangueil

Toulouse, 31000, France

Location

Related Publications (1)

• 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: 34725108 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Disease

Interventions

Everolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Lionel COUZI, MD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Rodolphe THIEBAUT, MD, PhD

  University Hospital, Bordeaux

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2014
• First Posted: December 31, 2014
• Study Start: May 2, 2014
• Primary Completion: October 10, 2018
• Study Completion: October 10, 2018
• Last Updated: November 14, 2018

Record last verified: 2018-11

Locations

FR (9)