- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01680861
Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium
Randomized, Open-Label Trial of Tacrolimus/Everolimus vs. Tacrolimus/Enteric-Coated Mycophenolate Sodium to Prevent Biopsy-Proven Acute Rejection and Chronic Allograft Injury in Adult, Primary Kidney Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A. Primary Objectives:
- The percentage of patients who develop chronic allograft injury (CAI) progression during the first 12 months post-transplant protocol biopsy (i.e., higher grade of IF/TA at either the 6 or 12 month protocol biopsy in comparison with the baseline biopsy).
- The incidence rate of biopsy-proven acute rejection (BPAR) during the first 12 months post-transplant.
B. Secondary Objectives:
- Adverse events including graft loss (death-censored and death-uncensored), and death at 12 months post-transplant.
- Incidence rate and severity (severity of CAI at 12 months as well), based upon careful review of all clinically indicated and protocol biopsies.
- Renal function as determined by serum creatinine and estimated glomerular filtration rate (eGFR) (calculated using the abbreviated MDRD formula) at 12, months post-transplant. Use of multivariable analysis to compare renal function as well as BPAR and CAI progression will also be performed (particularly, after adjusting for the significant effects of donor age, recipient age, race/ethnicity, and any other predictors).
5. Adverse events including withholding (for ≥ 28 days) or discontinuance of study medications (and reasons why), new onset diabetes mellitus after transplantation (NODAT), infections requiring hospitalization, and requirement of anti-lipid medication at 12 months post-transplant.
6. Avoidance of the requirement for maintenance corticosteroid therapy after renal transplantation.
7. Allowance of reduced maintenance tacrolimus dosing (rTd).
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- University of Miami
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tacrolimus and Everolimus
Patients in both arms will receive reduced tacrolimus dosing (rTd), 0.1 mg/kg PO divided in two daily doses - beginning when serum Cr decreases to a level of <4 mg/dl (i.e., acceptable renal transplant function) postoperatively. Target tacrolimus trough levels during the first year post-transplant and thereafter will be 5-8 ng/ml. Everolimus initiated within 24 hours post-transplant (i.e., immediately following randomization) at 0.75mg PO BID and will be adjusted in order to achieve target everolimus trough levels of 3-8 ng/ml. |
Tacrolimus dosing (rTd) is planned, 0.1 mg/kg PO BID - beginning when serum Cr decreases to a level of <4 mg/dl (i.e., acceptable renal transplant function) postoperatively.
Target tacrolimus trough levels during the first year post-transplant and thereafter will be 5-8 ng/ml.
Other Names:
Everolimus initiated at 0.75 PO BID and will be adjusted in order to achieve target everolimus trough levels of 3-8 ng/ml.
Other Names:
Corticosteroids will be given as per our center protocol, i.e., a bolus of 500 mg of Methylprednisolone intravenously at surgery and daily x2, followed by 1.0 mg/kg, then 0.5 mg/kg orally until weaned off completely by 7-10 days postoperatively - the plan is for corticosteroids to be discontinued by 7-10 days postoperatively in both groups.
Other Names:
|
Active Comparator: Tacrolimus and Enteric-Coated Mycophenolate Sodium (EC-MPS)
Patients in both arms will receive reduced tacrolimus dosing (rTd), 0.1 mg/kg PO divided in two daily doses - beginning when serum Cr decreases to a level of <4 mg/dl (i.e., acceptable renal transplant function) postoperatively. Target tacrolimus trough levels during the first year post-transplant and thereafter will be 5-8 ng/ml. EC-MPS will be initiated at 720 mg PO BID starting on the first post-operative day. |
Tacrolimus dosing (rTd) is planned, 0.1 mg/kg PO BID - beginning when serum Cr decreases to a level of <4 mg/dl (i.e., acceptable renal transplant function) postoperatively.
Target tacrolimus trough levels during the first year post-transplant and thereafter will be 5-8 ng/ml.
Other Names:
Corticosteroids will be given as per our center protocol, i.e., a bolus of 500 mg of Methylprednisolone intravenously at surgery and daily x2, followed by 1.0 mg/kg, then 0.5 mg/kg orally until weaned off completely by 7-10 days postoperatively - the plan is for corticosteroids to be discontinued by 7-10 days postoperatively in both groups.
Other Names:
EC-MPS 720 mg PO BID - beginning on 1st postoperative day.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
BPAR (Biopsy-proven Acute Rejection) Incidence During the First 12 Months Post-transplant
Time Frame: 1 year
|
BPAR (biopsy-proven acute rejection) incidence during the first 12 months post-transplant.
Grading is determined using standard Banff criteria.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Chronic Allograft Nephropathy (CAI) at 12 Months Post-transplant
Time Frame: 1 year
|
Incidence of (biopsy-proven) chronic allograft nephropathy (CAI) [interstitial fibrosis and tubular atrophy, using standard Banff criteria] at 12 months post-transplant.
|
1 year
|
Graft Loss (Return to Permanent Dialysis or Death)
Time Frame: during the first 12 months post-transplant
|
during the first 12 months post-transplant
|
|
eGFR (Calculated Glomerular Filtration Rate), i.e., Renal Function, at 1 Month Post-transplant.
Time Frame: at 1 month post-transplant
|
using the abbreviated MDRD formula.
|
at 1 month post-transplant
|
eGFR (Renal Function) at Month 3 Post-transplant
Time Frame: at 3 months post-transplant
|
Renal function as determined by the estimated glomerular filtration rate (eGFR) at 3 months post-transplant, using the abbreviated MDRD formula.
|
at 3 months post-transplant
|
eGFR (Renal Function) at 6 Months Post-transplant
Time Frame: at 6 months post-transplant
|
using the abbreviated MDRD formula.
|
at 6 months post-transplant
|
Discontinuance of Any Study Medication (Tacrolimus, Everolimus, or EC-MPS)
Time Frame: during the first 12 months post-transplant
|
during the first 12 months post-transplant
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gaetano Ciancio, M.D., University of Miami
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Kidney Diseases
- Urologic Diseases
- Renal Insufficiency
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Neuroprotective Agents
- Protective Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Methylprednisolone
- Tacrolimus
- Mycophenolic Acid
- Everolimus
Other Study ID Numbers
- 20110126
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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