Absence; Kidney
Conditions
Brief summary
This study's focus is to compare the level effectiveness and safety of regimens involving Sirolimus, Cellcept and steroid to Prograf, Sirolimus and steroid in African-American recipients of kidney transplants.
Detailed description
A major concern in transplantation is finding a successful regimen of medications to lower the potential for the body to reject the newly transplanted organ. The regimens in kidney transplantation include tacrolimus, sirolimus, mycophenolate mofetil and steroids. This study will compare the effectiveness and safety of a regimen including Sirolimus, Prograf, and steroids compared to a regimen including Sirolimus, Cellcept and steroids. These regimens have already been researched in the Caucasian population, and both drug regimens are FDA approved. This study's focus is on the effectiveness and safety of these regimens in African-Americans.
Interventions
DRUGrapamune, mycophenolate mofetil and steroid
At the time of transition patients randomized into this arm of the study will receive loading doses of sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml. Patients randomized into this arm of the study will continue their current dosing regimen and frequency of mycophenolate mofetil. Serum trough level monitoring of mycophenolic acid will not be performed unless clinically warranted per standard of care and dosage adjustments from such levels will be made only with consent of the study primary investigator.
DRUGtacrolimus, sirolimus and steroid
Tacrolimus dosing is based on 12-hour whole blood trough concentrations. Target blood concentration is 2-5 ng/ml. At the time of transition patients randomized into this arm of the study will receive loading doses of Sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age and able to give informed consent * African-American ethnicity * Received a first or second non-ECD cadaveric or living donor renal transplant * Transplant occurred during the past 6 to 24 weeks * Patient has stable graft function, defined as no change of greater than 30% of baseline serum creatinine during the past month and no acute rejection in the past 6 weeks * Estimated GFR using the modified MDRD equation of at least 40 mL/min10 at time of enrollment into the study * Currently receiving tacrolimus, mycophenolate mofetil (at least 1 gm per day), and corticosteroids as their immunosuppression regimen.
Exclusion criteria
* Biopsy proven acute rejection episode that occurred within the past 6 weeks * Malignancy within the past 3 years, except for non-melanoma skin cancer * Any known intolerances to current immunosuppressant regimen necessitating withdrawal of the offending agent * Currently enrolled in an investigational trial * Woman of child bearing potential not utilizing an effective form of birth control * Patients with uncontrolled dyslipidemia, defined at serum fasting LDL \>200 mg/dL or serum fasting triglycerides \>500 mg/dL. * Patients with a spot urine protein to creatinine ratio of \> 800 mg of protein per gram of creatinine. * WBC \< 3,000 cells/mm3 * Platelets \< 100,000 cells/mm3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness and Safety of a Particular Drug Regimen to Prevent Kidney Rejection | 12 months | Number of Participants with Kidney Rejections |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus Withdrawal Arm At the time of transition patients randomized into this arm of the study will receive loading doses of sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.
Patients randomized into this arm of the study will continue their current dosing regimen and frequency of mycophenolate mofetil. Serum trough level monitoring of mycophenolic acid will not be performed unless clinically warranted per standard of care and dosage adjustments from such levels will be made only with consent of the study primary investigator. | 23 |
| Tacrolimus Minimization Arm Tacrolimus dosing is based on 12-hour whole blood trough concentrations. Target blood concentration is 2-5 ng/ml.
At the time of transition patients randomized into this arm of the study will receive loading doses of Sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml. | 17 |
| Total | 40 |
Baseline characteristics
| Characteristic | Tacrolimus Withdrawal Arm | Tacrolimus Minimization Arm | Total |
|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 14 | 54 years STANDARD_DEVIATION 11 | 52 years STANDARD_DEVIATION 13 |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 19 Participants | 8 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 23 | 16 / 17 |
| serious Total, serious adverse events | 1 / 23 | 0 / 17 |
Outcome results
Primary
Effectiveness and Safety of a Particular Drug Regimen to Prevent Kidney Rejection
Number of Participants with Kidney Rejections
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus Withdrawal Arm | Effectiveness and Safety of a Particular Drug Regimen to Prevent Kidney Rejection | 4 participants |
| Tacrolimus Minimization Arm | Effectiveness and Safety of a Particular Drug Regimen to Prevent Kidney Rejection | 1 participants |