Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

A recent therapeutic strategy following renal transplantation includes simultaneous use of reduced calcineurin inhibitor (CNI) dosing and maximized use of a non-nephrotoxic, antiproliferative drug (inosine monophosphate dehydrogenase (IMPDH) or TOR inhibitor), with the goals of reducing/avoiding CNI nephrotoxicity, the incidence of acute rejection, and chronic allograft injury (CAI) (i.e., interstitial fibrosis/tubular atrophy), leading to more favorable longer-term patient and graft survival.1-7 Early corticosteroid withdrawal has also been used in the attempt to avoid well-known side effects while maintaining favorable patient and graft survival.8-10 While the investigators center and numerous other centers have also included single agent, antibody induction utilizing the lymphodepleting polyclonal antibody rabbit anti-human thymocyte globulin (ATG), nondepleting human anti-interleukin-2 receptor (CD25) monoclonal antibody daclizumab (Dac) or basiliximab, or lymphodepleting humanized anti-CD52 monoclonal antibody alemtuzumab,11-17 evidence now suggests that an even more effective induction strategy may include the combined use of more than one induction agent (each with fewer doses than if used alone), with the goal of bringing the kidney transplant recipient even closer (through more effectively timed lymphodepletion) to an optimally immunosuppressed state, allowing further reduction in long-term maintenance drug dosing.18-25 The investigators have now successfully used dual ATG/Dac induction therapy in both kidney-alone23-24 and simultaneous kidney-pancreas (SPK) transplantation,18-20 and a recent report from the investigators center of kidney-alone and SPK recipients shows that the addition of anti-CD25 to ATG for induction therapy more effectively delays the return of peripheral blood CD25+ cells.25 In the kidney-alone recipient study 3 doses of ATG were combined with 2 doses of Dac for induction,23-24 vs. the investigators previous studies utilizing single agent induction with 7 doses of ATG or 5 doses of Dac.4,16,17 Successful combination of ATG/basiliximab as dual induction in kidney transplantation has also been reported elsewhere,21-22 along with equivalency in clinical outcomes using daclizumab vs. basiliximab.13

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gaetano Ciancio
• Treatments: Everolimus; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Mycophenolate mofetil; Mycophenolic Acid; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Sirolimus; Tacrolimus

Criteria

Inclusion Criteria:

• Weight > 40 kg.

• Deceased donor (SCD) or LD.

• Donor-recipient 1 haplotype matched pairs with a minimum matching of 1 HLA DR antigen.

• Negative standard cross match for T cells.

• Pretransplant panel reactive antibodies of < 30%.

• Graft required to be functional, producing at least 100ml of urine within 24hr after transplantation.

Exclusion Criteria:

• Previously received or is receiving an organ transplant other than a kidney.

• Donor organ with a cold ischemic time > 48 hours.

• ABO incompatible donor kidney.

• Recipients of T cell, or B cell crossmatch positive transplant.

• Panel reactive antibody (PRA) >30%

• HIV or Hepatitis C virus, or Hepatitis B virus antigenemia.

• Current malignancy or a history of malignancy

• Liver disease

• Uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or an active peptic ulcer

• Use of warfarin, fluvastatin, or herbal supplements during the study.

• Use of astemizole, pimozide, cisapride, terfenadine, or ketoconazole.

• Hypersensitivity to thymoglobulin, IL-2 receptor inhibitor monoclonal antibodies, tacrolimus, everolimus, MPA, or corticosteroids.

• Pregnant or lactating.

• Abnormal screening/baseline labs WBC, platelet count, triglycerides, and cholesterol Double kidneys,ECD, pediatric en-block, and donation after cardiac death (DCD)