Renal Failure
Conditions
Keywords
Kidney, Kidney transplant, Renal failure, End Stage Renal Disease, kidney transplant recipient
Brief summary
This study is being done to compare the effectiveness and safety of two different kidney transplant immunosuppression drugs, Zortress (the study drug) and Rapamune (which is used in the current standard immunosuppression regimen).
Detailed description
Zortress is FDA approved, is used as standard of care at some other institutions, and may also be given as standard of care if it is believed to be the best immunosuppression regimen for a particular kidney transplant recipient. The rationale for testing Zortress vs. Rapamune is to determine which of these drugs is more effective in preventing chronic rejection of the transplanted kidney. Because these two drugs are related to each other there is no current literature addressing the replacement of Rapamune with Zortress in an immunosuppression regimen, therefore the goal of this study is to compare these two immunosuppression drugs.
Interventions
DRUGEverolimus
0.75mg twice a day, Orally, starting on day of transplant
DRUGSirolimus
5mg, Orally, starting on day of transplant; decreasing to 3mg
Sponsors
Novartis
Ohio State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients must give written informed consent before any assessment is performed. 2. Primary renal transplant recipients between ages 18 and 75 years of age. 3. Females capable of becoming pregnant must have a negative pregnancy test prior to transplantation and practice an effective form of birth control for the duration of the study and 12 weeks after discontinuation of the study drug if applicable.
Exclusion criteria
1. Total cholesterol \> 300 mg/dl or triglycerides \> 400 mg/dl despite lipid lowering therapy 2. Pre-existing bone marrow suppression (White Blood Cell count of \< 3000, platelets \< 100,000) 3. Active infection (Hepatitis B Virus, HIV) 4. Malignancy (except for adequately treated squamous or basal cell skin carcinoma) unless patient has written clearance from an Oncologist or if patient has had no malignancy for at least 2 years prior to the transplant 5. Allergy or intolerance to Zortress, Rapamune, cyclosporine, or Anti-thymocyte globulin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year | 1 Year | The primary objective of this pilot study will be to determine equivalency of Zortress® as compared to Rapamune® when used in our de novo immunosuppression regimen following renal transplantation. The primary endpoint will be a composite endpoint of graft survival (non-death censored) and biopsy proven acute rejection at 1 year. The primary outcome of immunosuppressive protection would be studied in our Thymoglobulin and rapid steroid discontinuation protocol, with half-dose Neoral as described above. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zortress (Everolimus) Zortress will be started on day of transplant and initially dosed at 0.75 mg twice a day (12 hours apart) dosed simultaneously with Neoral.
Everolimus: 0.75mg twice a day, Orally, starting on day of transplant | 41 |
| Rapamune (Sirolimus) Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d.
Sirolimus: 5mg, Orally, starting on day of transplant; decreasing to 3mg | 19 |
| Total | 60 |
Baseline characteristics
| Characteristic | Zortress (Everolimus) | Rapamune (Sirolimus) | Total |
|---|---|---|---|
| Age, Continuous | 49.7 years STANDARD_DEVIATION 11.9 | 49.5 years STANDARD_DEVIATION 12.2 | 49.6 years STANDARD_DEVIATION 11.9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 17 Participants | 5 Participants | 22 Participants |
| Sex: Female, Male Male | 24 Participants | 14 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 19 |
| other Total, other adverse events | 0 / 41 | 0 / 19 |
| serious Total, serious adverse events | 35 / 41 | 17 / 19 |
Outcome results
Primary
Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year
The primary objective of this pilot study will be to determine equivalency of Zortress® as compared to Rapamune® when used in our de novo immunosuppression regimen following renal transplantation. The primary endpoint will be a composite endpoint of graft survival (non-death censored) and biopsy proven acute rejection at 1 year. The primary outcome of immunosuppressive protection would be studied in our Thymoglobulin and rapid steroid discontinuation protocol, with half-dose Neoral as described above.
Time frame: 1 Year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zortress (Everolimus) | Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year | graft survival (non-death censored) at 1 year | 40 Participants |
| Zortress (Everolimus) | Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year | biopsy proven acute rejection at 1 year | 38 Participants |
| Rapamune (Sirolimus) | Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year | graft survival (non-death censored) at 1 year | 19 Participants |
| Rapamune (Sirolimus) | Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year | biopsy proven acute rejection at 1 year | 19 Participants |