Allograft, Graft Failure, Graft Rejection, Renal Failure , Chronic, Renal Failure Chronic Requiring Dialysis
Conditions
Keywords
Renal failure, immunosuppressor, HLA sensitization, Graft failure, Calcineurin inhibitors
Brief summary
The goal of this clinical trial is to compare the degree of HLA sensitization at 2 years in patients with late renal graft failure (\> 3 months) when receiving reduced immunosuppressant treatment versus stopping immunosuppression at 6 months. The main question this study aims to answer is: Does maintaining long-term immunosuppression in patients with a late renal graft failure (\> 3 months) safely reduce the risk of HLA sensitization? To answer this question, patients will be assigned to a control arm or investigational arm: * Patients assigned to the control arm will receive standard treatment, in which immunosuppressant treatment is withdrawn after 6 months. * Patients assigned to the investigatonal arm will continue immunosuppressant treatment at low doses for 2 years. Patients recruited in this clinical trial will be followed for up to 2 years. During this time, patients will visit the clinic every 3 months for checkups and tests.
Interventions
DRUGContinue low dose calcineurin inhibitor (CNI)
CNI dose (tacrolimus or cyclosporine) will be adjusted to maintain low tacrolimus or cyclosporine whole blood trough levels from month 3 to month 24 or End of Study
DRUGCalcineurin inhibitor withdrawal at 6 months
CNI dose (tacrolimus or cyclosporine) will be reduced to one-half on month 3 visit and completely withdrawn on month 6 visit.
Sponsors
Hospital Universitari Vall d'Hebron Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must be able to understand and provide written informed consent * Patients older than 18 years who had received at least one previous renal transplant * Patients with a retained kidney graft failed for any reason which survived at least 3 months * Patients on dialysis, either hemodialysis or peritoneal dialysis. Patients can be on dialysis for a maximum of 6 months at the time of randomization, as long as the patients have taken an uninterrupted immunosuppressive regimen of calcineurin inhibitors (tacrolimus or cyclosporine) and steroids since dialysis was restarted * Patients already relisted or candidates to relist to deceased donor kidney transplantation according to the treating physician criteria * Patients taking immunosuppressants tacrolimus or cyclosporine * cPRA at the time of randomization ≤ 90%
Exclusion criteria
* Patients who have received another solid organ transplantation (liver, lung, heart or pancreas) * Patients waiting for a living related / unrelated kidney transplant * Graft survival of the failed graft lower than 3 months * Patients in dialysis more than 6 months at the time of randomization * Patients not accomplishing criteria to relist in the transplantation list according to the treating physician criteria * Pregnant women * Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study. Patients should use one of the acceptable birth control measures recommended in the document Recommendations related to contraception and pregnancy testing in clinical trials published by the Clinical Trials Facilitation and Coordination Group (CTFG) (version 1.1, published 21/09/2020). Recommended birth control measures include oral, injected or implanted hormonal contraceptive, barrier methods (condom or diaphragm with spermicide), intrauterine device, surgical sterilization, transdermal delivery, or sexual abstinence. If sexually active, the subject must have been using one of the accepted birth control methods at least one month prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of HLA sensitization | 2 years | The difference between the two treatment arms in the degree of HLA sensitization at 2-years measured as cPRA (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days of hospitalization for any reason | 2 years | The difference between the two treatment arms at 2-years on days of hospitalization for any reason |
| Percentage of patients effectively relisted during follow-up | 2 years | The difference between the two treatment arms at 2-years on percentage of patients effectively relisted during follow-up |
| Percentage of patients transplanted | 2 years | The difference between the two treatment arms at 2-years on percentage of patients transplanted |
| Percentage of patients delisted for any reason | 2 years | The difference between the two treatment arms at 2-years on percentage of patients delisted for any reason |
| Incidence of infection | 2 years | The difference between the two treatment arms at 2-years on incidence of infection |
| Incidence of cardiovascular events | 2 years | The difference between the two treatment arms at 2-years on incidence of cardiovascular events |
| Mortality for any reason | 2 years | The difference between the two treatment arms at 2-years on mortality for any reason |
| Incidence of graft-intolerance syndrome requiring graft nephrectomy or percutaneous embolization of the non-functioning graft | 2 years | The difference between the two treatment arms at 2-years incidence of graft-intolerance syndrome requiring graft nephrectomy or percutaneous embolization of the non-functioning graft |
| Erythropoietin resistance index | 2 years | The difference between the two treatment arms at 2-years on erythropoietin resistance index |
| Residual renal function | 2 years | The difference between the two treatment arms at 2-years on residual renal function |
| Number of circulating memory B-cells | 2 years | The difference between the two treatment arms at 2-years on number of circulating memory B-cells |
| Adverse events | 2 years | The difference in the incidence of adverse events (AE) in the two treatment arms |
| Incidence of cancer | 2 years | The difference between the two treatment arms at 2-years on incidence of cancer |
Countries
Spain
Contacts
Primary ContactFrancesc Moreso, MD, PhD
Outcome results
None listed