Extended Release Tacrolimus vs. Twice-Daily Tacrolimus
Condition: End Stage Renal Disease; Rejection of Renal Transplant
MeSH terms: Kidney Failure, Chronic
Intervention: Tacrolimus; Tacrolimus Extended Release Oral Tablet [Envarsus]
Intervention description: immunosuppressive agent tacrolimus, given twice-daily; immunosuppressive agent extended-release tacrolimus, given once daily
Intervention MeSH terms: Tacrolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: immunosuppression

Summary:

      The overall aim of the study is to prospectively investigate the impact of two maintenance
      calcineurin inhibitor immunosuppressive regimens: once-daily extended release tacrolimus and
      twice-daily tacrolimus on subpopulations of T and B cells and alloreactive T cells as well as
      on renal allograft function.
    

Eligibility criteria:

        Inclusion Criteria:

        1. Patients who are males or females aged 18-65 years. 2. Use of the following induction
        medications: basiliximab and rituximab. 2. Donors aged 18-65 years. 3. No prior organ
        transplant 4. Patients who are single-organ recipients (kidney only). 5. Women who are of
        childbearing potential must have a negative serum pregnancy test before transplantation and
        agree to use a medically acceptable method of contraception throughout the treatment
        period.

        6. Subject (recipient) is able to understand the consent form and give written informed
        consent

        Exclusion Criteria:

          1. Delayed graft function (please see above).

          2. Known sensitivity or contraindication to alemtuzumab, Envarsus® XR, tacrolimus or MMF.

          3. Use of the following induction medications: basiliximab and rituximab

          4. Patient with significant or active infection.

          5. Patients with a positive flow cytometric crossmatch using donor lymphocytes and
             recipient serum.

          6. Patients with PRA > 40%

          7. Patients with current or historic donor specific antibodies

          8. Body Mass Index (BMI) of < 18 or > 35

          9. Patients who are pregnant or nursing mothers.

         10. Patients whose life expectancy is severely limited by diseases other than renal
             disease.

         11. Ongoing active substance abuse, drug or alcohol.

         12. Major ongoing psychiatric illness or recent history of noncompliance.

         13. Significant cardiovascular disease (e.g.):

               -  Significant non-correctable coronary artery disease;

               -  Ejection fraction below 30%;

               -  History of recent myocardial infarction.

         14. Malignancy within 3 years, excluding non-melanoma skin cancers.

         15. Serologic evidence of infection with HIV or HBVs-Ag positive.

         16. Patients with a screening/baseline total white blood cell count < 4,000/mm3; platelet
             count < 100,000/mm3; triglyceride > 400 mg/dl; total cholesterol > 300 mg/dl.

         17. Investigational drug within 30 days prior to transplant surgery.

         18. Anti-T cell therapy within 30 days prior to transplant surgery.

         19. Diagnosis of atypical-Hemolytic Uremic Syndrome (aHUS).

         20. Subjects transplanted with a Hepatitis C NAT-positive kidney.