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| ID | Type | Description | Link |
|---|---|---|---|
| CRAD001AUS196T | Other Identifier |
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Patients meeting the inclusion/ exclusion criteria did not agree to participate. It became obvious that recruitment goals could not be met.
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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
The investigators hypothesize that switching kidney transplant patients on tacrolimus/sirolimus long-term maintenance immunosuppressive drug regimens to tacrolimus/everolimus, will not only be safe, but will lead to better kidney function than patients staying on tacrolimus/sirolimus due to the lower potential of everolimus to enhance calcineurin inhibitors toxicity and/or its ability to even reverse some of the negative effects of calcineurin inhibitors on vascular endothelial and kidney function. To test this hypothesis vascular endothelial biomarkers will be analyzed in blood plasma samples and kidney dysfunction biomarkers in urine samples via liquid chromatography tandem mass spectrometry to evaluate whether switching kidney transplant patients on tacrolimus/sirolimus to tacrolimus/everolimus will lead to better kidney and endothelial function after one year and two years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Everolimus / Tacrolimus | Experimental | Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/everolimus arm of the study will be switched from sirolimus to everolimus 1:1 (same sirolimus as everolimus dose). Everolimus doses will be adjusted so that trough blood concentrations are within 3-8 ng/mL. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, twice a day) in combination with Everolimus (Zortress, 0.25, 0.5 and 0.75 tablets). |
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| Sirolimus / Tacrolimus | Active Comparator | Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/sirolimus arm of the study will remain on tacrolimus/sirolimus. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, once a day) in combination with Sirolimus (Rapamune, 0.5, 1, and 2mg tablets). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Everolimus | Drug | Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/everolimus arm of the study will be switched from sirolimus to everolimus 1:1 (same sirolimus as everolimus dose). Everolimus doses will be adjusted so that trough blood concentrations are within 3-8 ng/mL. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, twice a day) in combination with Everolimus (Zortress, 0.25, 0.5 and 0.75 tablets). |
| Measure | Description | Time Frame |
|---|---|---|
| Creatinine Outcome Measure (1) | Kidney function outcome markers will be assessed one year after kidney transplant | 1 year |
| Calculated Glomerular Filtration Rate (1) | Kidney function outcome markers will be assessed one year after kidney transplant | 1 year |
| Calculated Glomerular Filtration Rate (2) | Kidney function outcome markers will be assessed two years after kidney transplant | 2 years |
| Kidney Injury Molecule-1 (1) | Kidney function outcome markers will be assessed one year after kidney transplant | 1 year |
| Kidney Injury Molecule-1 (2) | Kidney function outcome markers will be assessed two years after kidney transplant | 2 years |
| S-Adenosylhomocysteine Hydrolase (1) | Kidney function outcome markers will be assessed one year after kidney transplant | 1 year |
| S-Adenosylhomocysteine Hydrolase (2) | Kidney function outcome markers will be assessed two years after kidney transplant | 2 years |
| S-Adenosylmethionine (1) | Kidney function outcome markers will be assessed one year after kidney transplant |
| Measure | Description | Time Frame |
|---|---|---|
| 12-Hydroxyeicosatetraenoic acid (1) | Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant | 1 year |
| 12-Hydroxyeicosatetraenoic acid (2) | Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Laurence Chan, MD, PhD | University of Colorado, Denver | Principal Investigator |
| Clifford Miles, MD, MS | University of Nebraska | Principal Investigator |
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| ID | Term |
|---|---|
| D000068338 | Everolimus |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Sirolimus | Drug | Patients will be stable kidney transplant patients who are receiving an immunosuppressive drug regimen based on tacrolimus and sirolimus. 24 hours after the last sirolimus dose, the patients randomized to the tacrolimus/sirolimus arm of the study will remain on tacrolimus/sirolimus. In detail: Tacrolimus (Prograf or FDA approved generic 0.5 mg, 1 mg or 5 mg capsules, once a day) in combination with Sirolimus (Rapamune, 0.5, 1, and 2mg tablets). |
|
| 1 year |
| S-Adenosylmethionine (2) | Kidney function outcome markers will be assessed two years after kidney transplant | 2 years |
| Creatinine Outcome Measure (2) | Kidney function outcome markers will be assessed two years after kidney transplant | 2 years |
| 2 years |
| 20-Hydroxyeicosatetraenoic acid (1) | Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant | 1 year |
| 20-Hydroxyeicosatetraenoic acid (2) | Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant | 2 years |
| 18- Hydroxyeicosapentaenoic acid (1) | Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant | 1 year |
| 18- Hydroxy- eicosapentaenoic acid (2) | Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant | 2 years |
| Ornithine (1) | Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant | 1 year |
| Ornithine (2) | Vascular endothelial dysfunction outcome markers will be assessed two years after kidney transplant | 2 years |
| Arginine (1) | Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant | 1 year |
| Arginine (2) | Vascular endothelial dysfunction outcome markers will be assessed one year after kidney transplant | 2 years |