Differentiating Everolimus Versus Sirolimus in Combination With Calcineurin Inhibitors in Kidney Transplant Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 2/7/2015 |
| Start Date: | December 2013 |
| End Date: | December 2016 |
| Contact: | Uwe Christians, MD, PhD |
| Email: | uwe.christians@ucdenver.edu |
| Phone: | 3037245665 |
Differentiating Sirolimus and Everolimus in Combination With Calcineurin Inhibitors in Long-term Maintenance of Kidney Transplant Patients - The Effects on Vascular Endothelial and Kidney Function. The DESIRE Study.
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.
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.
Inclusion Criteria:
- Kidney transplant patients ≥ 3 months after transplantation. De novo patients on
sirolimus and tacrolimus as well as patients switched to tacrolimus and sirolimus
will be eligible as long as they have received this drug combination for at least 2
months.
- Immunosuppressive drug regimen based on tacrolimus and sirolimus
- 18-70 years of age
- calculated glomerular filtration rate≥ 30 mL/min/ 1.73m2 as calculated using the
abbreviated Modification of Diet in Renal Disease formula
- Ability and willingness to provide written informed consent and adhere to study
regimen.
- Patients who are able to take oral medication at time of randomization.
Exclusion Criteria:
- Patients switched to tacrolimus and sirolimus due to clinically relevant
nephrotoxicity of the previous immunosuppressive drug regimen,
- Patients with an abnormal liver profile such as alanine aminotransferase, aspartate
aminotransferase, alkaline phosphatase, or total bilirubin > 3 x upper limit of
normal at time of randomization
- Patients with severe total hypercholesterolemia (> 350 mg/dL; > 9 mmol/L) or total
hypertriglyceridemia (> 500 mg/dL; > 5.6 mmol/L). Patients on lipid lowering
treatment with controlled hyperlipidemia are acceptable.
- Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen.
- An episode of acute rejection that required antibody therapy or more than one steroid
sensitive episode of acute rejection prior to enrollment.
- Spot urine protein/creatinine ratio > 1g/24h at the time of randomization
- Multi-organ transplants
- Patients with platelet count < 50,000
- Patients with an absolute neutrophil count of < 1,000 or white blood cells of <2,000
at time of enrollment
- Patients with hemoglobin < 6g/dL
- Patients with clinically significant systemic infections requiring active use of IV
antibiotics, anti-virales, or anti-fungals. Prophylactic use of anti-virales will be
acceptable.
- Pregnancy or inability of practicing acceptable contraceptive measures.
- Patients who have any surgical or medical condition, such as severe diarrhea, active
peptic ulcer disease, or uncontrolled diabetes mellitus, which in the opinion of the
investigator might significantly alter the absorption, distribution, metabolism
and/or excretion of study medication.
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