Clinical trial NCT04180085: Pilot Study: Interest of Belatacept As a Non-nephrotoxic Immunosuppressive Treatment in Cardiac Transplant Patients At Risk of Chronic Renal Failure (BELACOEUR)
Official title: Pilot Study: Interest of Belatacept As a Non-nephrotoxic Immunosuppressive Treatment in Cardiac Transplant Patients At Risk of Chronic Renal Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heart Transplant Failure
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2019-11-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Heart transplantation (TC) is the standard treatment for terminal heart failure. Chronic kidney disease (CKD) is a common complication responsible for increased mortality and morbidity. The main risk factors for progression to CKD are advanced age, pre-transplantation CKD, degradation of glomerular filtration rate (GFR) in the first year post-transplantation, and nephrotoxicity of calcineurin inhibitors (CNI).

Indeed, these molecules (cyclosporin and tacrolimus), the cornerstone of immunosuppressive treatment, have nephrotoxic effects in the short term (by a hemodynamic effect) and in the long term (by a pro-fibrosin effect).

In renal transplantation (TR), belatacept, a costimulation-inhibiting molecule, used de novo, without CNI, with induction by anti-receptor antibody of Interleukines 2, preserves kidney function. Despite this great advantage, its development is still hampered by a higher number of rejections compared to the CNI group in this originator study. Based on the experience gained in TR, which has since validated its use, the hypothesis is that in heart transplantation, belatacept (Nulojix) combined with minimization of CNI (with induction by antilymphocyte serum), could significantly improve glomerular filtration rate (GFR) in patients at risk of CKD (by removing them from dialysis and possible kidney transplantation) without increasing the risk of rejection.


Eligibility criteria: Inclusion Criteria:

Cardiac transplant patients for 3 months Over 18 years of age No Donor Specific Antibodies at inclusion (positive threshold average fluorescence intensity (MFI)\> 2000) Having a GFR (DFG in french) is the single best indicator of overall renal function \< 30ml/min calculated according to the formula CKD EPI or a decrease in GFR of more than 50% between the day of the heart transplant and 3 months, stable for 15 days.

Induction treatment with anti-lymphocyte serum Virus d'Epstein-Barr positive serology Having signed the consent after receiving informed information Negative pregnancy test for patients of childbearing age, and agreement to use effective contraception throughout the study and 6 weeks after the end of the study Having no difficulty in understanding and communicating with the investigator and his representatives Beneficiaries of a Social Security scheme

Exclusion Criteria:

The criteria for non-inclusion are:

2nd heart transplant or other solid organ transplant History of rejections Cellular or humoral rejection at myocardial biopsy of 3 months post Transplantation Cardiac Current viral infection of type cytomegalovirus, Virus d'Epstein-Barr, hepatitis C virus, hepatitis V virus.....

Human immunodeficiency virus positive serology Ongoing participation in another clinical study Any clinical condition that the investigator considers incompatible with the conduct of the study under acceptable safety conditions: (in particular, progressive infection, progressive cardiovascular complication, progressive neoplastic disease) Inability of the patient to comply with study procedures Pregnant or breastfeeding women Person under guardianship, curators or safeguard of justice

Primary outcomes:
measure: Clearance
timeFrame: 12 months
Secondary outcomes:
measure: Myocardial biopsies
timeFrame: 12 months
measure: Anti-human leukocyte antigen antibody assay
timeFrame: 12 months
measure: Fasting blood glucose and glycated haemoglobin (HBA1C)
timeFrame: 12 months
measure: Death
timeFrame: 12 months
measure: Number of dialysis sessions
timeFrame: 12 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Karine Nubret
city: Lyon
country: France
facility: Laurent Sebbag
city: Nantes
country: France
facility: Claire Garandeau
city: Rennes
country: France
facility: Bertrand Lelong
Study officials:
References: