Kidney Transplantation
Conditions
Keywords
mycophenolate, living donor
Brief summary
This randomized trial will enroll adult recipients of HLA-identical living kidney transplants who are at least 1 year post-transplant. All subjects will be taking Prograf (tacrolimus) or cyclosporine and mycophenolic acid (CellCept or Myfortic) and then be randomized (1:2) to either continue calcineurin inhibitors or to taper off of calcineurin inhibitors. The hypothesis is that mycophenolic acid monotherapy permits long-term rejection-free renal allograft function in the absence of long-term calcineurin inhibitors in this fully matched renal transplant cohort.
Detailed description
The objective of the study is to safely move HLA-identical renal transplant recipients from 2 immunosuppressive drugs (calcineurin inhibitor and mycophenolic acid) to mycophenolic acid monotherapy. Safety will be assessed by monitoring renal function in subjects in the withdrawal group compared to those who remain on the standard 2-drug immunosuppression protocol. Results of immunological monitors such as DTH regulation in response to donor minor antigens and development of anti-donor antibodies will be correlated with successful withdrawal.
Interventions
DRUGMycophenolic Acid
Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months
DRUGStandard of Care: CNI and MPA
Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Sponsors
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects 18-75 years of age. * Subjects who are recipients of HLA-identical living donor renal allografts from a sibling and are at least 1 year post transplant, their donors and mothers. * Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.
Exclusion criteria
* GFR \<40ml/min; * diagnosis of SLE, * Subjects with proteinuria (defined as a protein:creatinine ratio of \>1 or an amount less than this deemed significant on an individual subject basis by the principal investigator),, * multi-organ transplant; * known hypersensitivity to, Prograf, Neoral, CellCept or Myfortic; * history of documented post transplant non-compliance with medications, transplant clinic or laboratory follow-up; * therapy with an investigational immunosuppressive drug within 6 weeks of study entry; * history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study; * patients on less than 500 mg PO BID of CellCept or 360 mg PO BID of Myfortic at the time of potential randomization, * history of humoral rejection post transplant, * maintenance or for cause treatment with steroids (prednisone) within 3 months of enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Kidney Allograft Rejection and Graft Loss | 36 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Function Measured by Serum Creatinine and eGFR | 36 months | — |
| Number of Incidences of Infection and Malignancy | 36 months | Number of incidences of infection and malignancy will be reported. |
| Patient Survival | 36 months | patient survival |
| Trans-vivo Delayed Type Hypersensitivity (DTH) Assay | 36 months | Delayed type hypersensitivity (DTH) reactivity status to donor and minor antigens will be detected using trans-vivo DTH assay. This information will help determine if T-regulatory cells are present, and whether such cells predict outcome of Calcineurin inhibitor withdrawal. |
Countries
United States
Participant flow
Pre-assignment details
Out of 16 enrolled participants,1 participant never got randomized and 1 participant did not show up for any of the appointments. Only 14 started in the study.
Participants by arm
| Arm | Count |
|---|---|
| MPA Monotherapy Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy
Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months | 5 |
| Control: MPA and CNI Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus)
Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months | 9 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | The study was closed prematurely | 5 | 9 |
Baseline characteristics
| Characteristic | MPA Monotherapy | Control: MPA and CNI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 12 Participants |
| Region of Enrollment United States | 5 participants | 9 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Incidence of Kidney Allograft Rejection and Graft Loss
Time frame: 36 months
Population: The study was closed prematurely. Data were not collected
Secondary
Number of Incidences of Infection and Malignancy
Number of incidences of infection and malignancy will be reported.
Time frame: 36 months
Population: The study was closed prematurely. No data was collected
Secondary
Patient Survival
patient survival
Time frame: 36 months
Population: The study was closed prematurely. Data were not collected
Secondary
Renal Function Measured by Serum Creatinine and eGFR
Time frame: 36 months
Population: The study was closed prematurely. No data was collected
Secondary
Trans-vivo Delayed Type Hypersensitivity (DTH) Assay
Delayed type hypersensitivity (DTH) reactivity status to donor and minor antigens will be detected using trans-vivo DTH assay. This information will help determine if T-regulatory cells are present, and whether such cells predict outcome of Calcineurin inhibitor withdrawal.
Time frame: 36 months
Population: The study was closed prematurely. Data were not collected