Cytomegalovirus Infection Clinical Trial
— EVERCMVOfficial 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®).
Verified date | November 2018 |
Source | University Hospital, Bordeaux |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 186 |
Est. completion date | October 10, 2018 |
Est. primary completion date | October 10, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: - 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: 1. Absolute neutrophil count (ANC) > 1000 cells/µL. 2. Platelet count > 50,000 cells/µL. 3. 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. |
Country | Name | City | State |
---|---|---|---|
France | CHU de Bordeaux | Bordeaux | |
France | CHU La Cavale Blanche | Brest | |
France | CHRU Caen - Hôpital de Caen | Caen | |
France | CHU de Limoges - Hôpital Dupuytren | Limoges | |
France | Hôpital Edouard Herriot | Lyon | |
France | APHP - Hôpital Necker | Paris | |
France | APHP - Kremlin Bicetre | Paris | |
France | CHRU Strasbourg | Strasbourg | |
France | CHU de Toulouse - Hôpital Rangueil | Toulouse |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Bordeaux | Novartis |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | 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). | 6 and 12 months post-transplantation | |
Secondary | Proportion of patient with graft loss, death and loss of follow-up | 12 months post-transplantation | ||
Secondary | Proportion of patient with acute rejection, graft loss, death and loss of follow-u | 12 months | ||
Secondary | Level to the first CMV DNAemia | Throughout the study | ||
Secondary | Time to the first CMV disease | Throughout the study | ||
Secondary | Proportion of patients treated for CMV infection in both groups | 6 months | ||
Secondary | Half-life of decreasing of DNAemia | after initiation of anti-CMV therapy | ||
Secondary | Occurrence of treatment failure, defined as the absence of viral eradication. | Day 49 (or 8 weeks) after the initiation of anti-CMV therapy | ||
Secondary | Occurrence of CMV mutation (UL97 ou UL54) associated with a resistance to an anti-CMV therapy. | Throughout the study | ||
Secondary | Graft function | Graft function defined as glomerular filtration rate (GFR) estimated by simplified MDRD formula and proteinuria/creatininuria ratio. | 6 and 12 months post-transplantation | |
Secondary | Proportion of patients with biopsy-proven acute rejection (BPAR) | 6 and 12 months post-transplantation | ||
Secondary | Degree of interstitial fibrosis/tubular atrophy | 12 months on protocol biopsies | ||
Secondary | Graft and patient survival | 6 and 12 months post-transplantation | ||
Secondary | Proportion of BK virus viremia | month 1, 3, 6 and 12 | ||
Secondary | Proportion of patients with adverse events (AE) and/or serious adverse events (SAE) including opportunistic infections and neoplasias. | 12 months | ||
Secondary | Proportion of patients with haematological disorders | The proportion of patients with haematological disorders (neutropenia, anaemia, thrombopenia) | 12 months | |
Secondary | Proportion of patients with diarrhea | 12 months | ||
Secondary | Proportion of dyslipidemia | 12 months | ||
Secondary | Proportion of patients with occurrence of New Onset Diabetes Mellitus as defined by American Diabetic Association (ADA) criteria. | 12 months | ||
Secondary | Proportion of patients who will discontinue the immunosuppressive treatment and the reasons why. | 12 months | ||
Secondary | Proportion of patients with delayed graft function | 12 months | ||
Secondary | Proportion of lymphocele | 12 months | ||
Secondary | Time to the first CMV DNAemia | Throughout the study |
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