End Stage Renal Disease, Kidney Transplantation
Conditions
Brief summary
African Americans receiving a kidney transplant are considered at high risk for early rejection of their transplanted kidney and require more immunosuppression to maintain their kidney transplant function. This increase in immunosuppression puts this group at risk for drug-related toxicities and complications such as post-transplant diabetes. This study will evaluate: 1. Whether a sirolimus based steroid avoidance regimen in African Americans may decrease the risks of drug-related toxicities, 2. Decreased rates of metabolic complications such as post-transplant diabetes, 3. The effect of Sirolimus plus a reduced dose cyclosporine on renal allograft function.
Detailed description
This is an open labeled prospective trial with race matched historical controls. The treatment group (experimental arm) will be African American de novo solitary renal transplant recipients. The control arm will consist of race matched solitary renal transplant recipients who received a Cyclosporine (CsA) -based immunosuppressive regimen. The subjects will be matched for organ source (living donor vs. cadaveric). The experimental treatment arm will have an immunosuppression regimen consisting of Sirolimus, Reduced dose cyclosporine, Thymoglobulin, and only 3 doses of steroids.
Interventions
DRUGSirolimus
Thymoglobulin induction, sirolimus and no maintenance corticosteroid
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* African American recipient race * Solitary cadaveric or living donor renal transplantation * Age ≥18years at the time of transplantation * Negative pregnancy serum test in females with childbearing potential
Exclusion criteria
* Age \< 18 years at the time of transplantation * Multi-organ transplant recipient * Currently taking steroids * White Blood Cell Count \< 3,000 * Platelet count \< 100,000 * Triglycerides \>400mg/dL * Cholesterol \> 350 mg/dL * Unwillingness to comply with study procedures * Allergic reaction to sirolimus Allergy to polyclonal antilymphocyte drugs (Thymoglobulin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative One-year Acute Rejection Rates | 12 months | To test the efficacy of Sirolimus (SRL)-based steroid avoidance regimen in high risk de novo renal allograft recipients. Efficacy endpoints for this objective is: cumulative one-year acute rejection rates of the transplant |
| One-year Graft Survival | 12 months | To test the efficacy of SRL-based steroid avoidance regimen in high risk de novo renal allograft recipients. Efficacy endpoints for this objective is: one-year graft survival |
| One-year Patient Survival | 12 months | To test the efficacy of SRL-based steroid avoidance regimen in high risk de novo renal allograft recipients. Efficacy endpoints for this objective is: one-year patient survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Post Transplant Diabetes | 12 months | To determine whether SRL-based steroid avoidance maintenance regimen is associated with decreased rates of metabolic complications. Endpoint is incidence of posttransplant diabetes mellitus |
| Drug-treated Dyslipidemic Syndrome | 12 months | To determine whether SRL-based steroid avoidance maintenance regimen is associated with decreased rates of metabolic complications. Endpoint is drug-treated dyslipidemic syndrome |
| Blood Pressure Control | 12 months | To determine whether SRL-based steroid avoidance maintenance regimen is associated with decreased rates of metabolic complications. Endpoint is number of people who had their blood pressure in the target control range with or without medication |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sirolimus, Steroid Avoidance Arm Thymoglobulin induction, sirolimus and no maintenance corticosteroid.
Sirolimus: Thymoglobulin induction, sirolimus and no maintenance corticosteroid | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 5 |
Baseline characteristics
| Characteristic | Sirolimus, Steroid Avoidance Arm |
|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 13.1 |
| Region of Enrollment United States | 44 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 44 |
| other Total, other adverse events | 0 / 44 |
| serious Total, serious adverse events | 0 / 44 |
Outcome results
Primary
Cumulative One-year Acute Rejection Rates
To test the efficacy of Sirolimus (SRL)-based steroid avoidance regimen in high risk de novo renal allograft recipients. Efficacy endpoints for this objective is: cumulative one-year acute rejection rates of the transplant
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus, Steroid Avoidance Arm | Cumulative One-year Acute Rejection Rates | 7 Participants |
p-value: 0.28Mantel Haenszel
Primary
One-year Graft Survival
To test the efficacy of SRL-based steroid avoidance regimen in high risk de novo renal allograft recipients. Efficacy endpoints for this objective is: one-year graft survival
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus, Steroid Avoidance Arm | One-year Graft Survival | 42 Participants |
p-value: 0.7Kaplan-Meier
Primary
One-year Patient Survival
To test the efficacy of SRL-based steroid avoidance regimen in high risk de novo renal allograft recipients. Efficacy endpoints for this objective is: one-year patient survival
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus, Steroid Avoidance Arm | One-year Patient Survival | 44 Participants |
Secondary
Blood Pressure Control
To determine whether SRL-based steroid avoidance maintenance regimen is associated with decreased rates of metabolic complications. Endpoint is number of people who had their blood pressure in the target control range with or without medication
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus, Steroid Avoidance Arm | Blood Pressure Control | 34 Participants |
Secondary
Drug-treated Dyslipidemic Syndrome
To determine whether SRL-based steroid avoidance maintenance regimen is associated with decreased rates of metabolic complications. Endpoint is drug-treated dyslipidemic syndrome
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus, Steroid Avoidance Arm | Drug-treated Dyslipidemic Syndrome | 21 Participants |
Secondary
Incidence of Post Transplant Diabetes
To determine whether SRL-based steroid avoidance maintenance regimen is associated with decreased rates of metabolic complications. Endpoint is incidence of posttransplant diabetes mellitus
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sirolimus, Steroid Avoidance Arm | Incidence of Post Transplant Diabetes | 9 Participants |