Phase 3
N=32
Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium
Transplant; Failure, Kidney
Bottom Line
View on ClinicalTrials.gov: NCT01680861 ↗Enrolled (actual)
32
Serious AEs
26.7%
Results posted
Dec 2016
Primary outcome: Primary: BPAR (Biopsy-proven Acute Rejection) Incidence During the First 12 Months Post-transplant — 1; 3 participants — p=0.32
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Tacrolimus (Drug); Everolimus (Drug); Enteric Coated Mycophenolate Sodium (EC-MPS) (Drug); Corticosteroids (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Gaetano Ciancio
- Primary completion
- Dec 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY BPAR (Biopsy-proven Acute Rejection) Incidence During the First 12 Months Post-transplant |
1; 3 | 0.32 |
| SECONDARY Incidence of Chronic Allograft Nephropathy (CAI) at 12 Months Post-transplant |
3; 3 | 0.99 |
| SECONDARY Graft Loss (Return to Permanent Dialysis or Death) |
0; 0 | 1.0 |
| SECONDARY eGFR (Calculated Glomerular Filtration Rate), i.e., Renal Function, at 1 Month Post-transplant. |
82.1; 62.1 | 0.06 |
| SECONDARY eGFR (Renal Function) at Month 3 Post-transplant |
75.7; 65.6 | 0.18 |
| SECONDARY eGFR (Renal Function) at 6 Months Post-transplant |
66.7; 63.7 | 0.65 |
| SECONDARY Discontinuance of Any Study Medication (Tacrolimus, Everolimus, or EC-MPS) |
0; 1 | — |
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
Eligibility 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 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)
Data sourced from ClinicalTrials.gov (NCT01680861). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.