CMV infection in CMV-seropositive de novo kidney transplant recipients receiving an immunosuppressive regimen.
Conditions
Interventions
Trade Name: MYFORTIC
Product Name: Mycophenolate
Product Code: Mycophenolate
Pharmaceutical Form: Tablet
Trade Name: CERTICAN
Product Name: Everolimus
Product Code: Everolimus
Pharmaceutical Form: Ta
Sponsors
CHU de Bordeaux
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years 2) End stage kidney disease and a suitable candidate for primary renal transplantation or re-transplantation 3) Patient seropositive for CMV (confirmed within two weeks post-transplant) and having received an allograft from a CMV seropositive or seronegative donor 4) Receiving a kidney transplant from a deceased or living donor with compatible ABO blood type 5) 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 6) Total ischemia time below 36 hours 7) Capable of understanding the purpose and risks of the study 8) Fully informed and having given written informed consent (signed Informed Consent has been obtained) 9) Affiliation to the social security regimen Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) CMV seronegative patient 2) Historical or current TGI (French equivalence of calculated PRA) > 85 % 3) Presence of historical or current anti-HLA donor specific antibodies 4) Patient who received anti-CMV therapy within the past 30 days prior to screening 5) Receiving or having previously received an organ transplant other than a kidney 6) Receiving a graft from a non-heart-beating donor 7) 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 8) Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer 9) Known allergy or intolerance to everolimus, valganciclovir, ganciclovir, mycophenolic acid, basiliximab, corticosteroids, or cyclosporine A or any of the product excipients 10) 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 11) Patient has adequate hematological post-transplant defined as: a) Absolute neutrophil count (ANC) > 1000 cells/µL b) Platelet count > 50,000 cells/µL c) Hemoglobin > 8.0 g/dL 12) Requiring initial therapy with induction immunosuppressive antibody preparations, such as anti-thymocyte globulins or rituximab or IVIG 13) Currently participating in another clinical trial investigating drugs. Observational studies are not considered as an exclusion criteria 14) Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator 15) Unlikely to comply with the visits scheduled in the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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®).;Timepoint(s) of evaluation of this end point: 6 months after kidney graft.;Secondary Objective: • The time to the first CMV disease • Incidence of CMV disease • The proportion of patient with acute rejection, graft loss, death and loss of follow-up at 12 months post-transplantation • Hystological and kidney consequences of CMV infections in both groups • The proportion of BK virus viremia at month 1, 3, 6 and 12 • Anti-CMV immunological response • The proportion of patients with adverse events (AE) and/or serious adverse events (SAE) including opportunistic infections and neoplasias • The proportion of patients with haematological disorders (neutropenia, anaemia, thrombopenia) • The proportion of patients who will discontinue the immunosuppressive treatment and the reasons why • The proportion of patients with delayed graft function • The proportion of Lymphocele;Primary end point(s): The composite of graft loss, death, loss of follow-up and CMV infection at 6 months post-transplantation. CMV infection will be defined by a single positive whole blood CMV PCR. To standardize the results of the CMV PCR between the different centers the WHO international standard provided by the NIBSC (National Institute for Biological Standards and Control) will be used by all the participating virological laboratories. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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). • The proportion of patient with graft loss, death and loss of follow-up at 12 months post-transplantation. • The proportion of patient with acute rejection, graft loss, death and loss of follow-up at 12 months post-transplantation. • The time and the level to the first CMV DNAemia. • Graft and patient survival at 6 and 12 months post-transplantation • The time to the first CMV disease. • The proportion of patients treated for CMV infection in both groups within the first 6 months • Half-life of decreasing of DNAemia after initiation of anti-CMV therapy. • The occurrence of treatment failure, defined as the absence of viral eradication at Day 49 (or 8 weeks) after the initiation of anti-CMV therapy • The occurrence of CMV mutation (UL97 ou UL54) associated with a resistance to an anti-CMV therapy • Graft function defined as glomerular filtration rate (GFR) estimated by simplified MDRD formula and proteinuria/creatininuria ratio at 6 and 12 months post-transplantation. • The proportion of patients with biopsy-proven acute rejection (BPAR) at 6 and 12 months post-transplantation • Degree of interstitial fibrosis/tubular atrophy at 12 months on protocol biopsies • The proportion of donor anti-HLA antibodies • The proportion of BK virus viremia at month 1, 3, 6 and 12. • The proportion of patients with adverse events (AE) and/or serious adverse events (SAE) including opportunistic infections and neoplasias • The proportion of patients with haematological disorders (neutropenia, anaemia, thrombopenia) • The proportion of patients with diarrhea • The proportion of patients who will discontinue the immunosuppressive treatment and the reasons why • The proportion of patients with delayed graft function • The proportion of lymphocele • The proportion of patients with | — |
Countries
France
Outcome results
None listed