Effects of Inhibiting Early Inflammation in Kidney Transplant Patients
Condition: Kidney Transplant
Intervention: Infliximab; Methylprednisolone; Mycophenolate Mofetil; Tacrolimus; Thymoglobulin®; Acetaminophen; Loratadine; Placebo for Infliximab; Prednisone; Diphenhydramine
Intervention description: A single dose, of 3mg/kg infusion; 500mg will be Initiated just prior to or at the initiation of transplant surgery and prior to Infliximab and thymoglobulin infusion; Administered at a target dose of 2000mg daily, as tolerated, until study closure; Administered at a target dose of 0.1mg/kg BID, post-op, then adjusted to target trough levels of 8-12ng/ml during 1st 3-months post-op and finally adjusted to target trough levels of 5-8ng/ml until study closure; Administered daily for 5 days with the intention of achieving a total dose of 4.5 to 6.0 mg/kg, as tolerated; 30 to 60 minutes prior to the start of the infusion
Tylenol, 600 to 1000mg by mouth or
Suppository form; 30 to 60 minutes prior to the start of the infusion
Claritin (Loratadine) 10mg by mouth or
Benadryl (Diphenhydramine) 25 or 50 mg by mouth; A single dose is volume matched to Infliximab (250mL) infusion; Prednisone will be administered peri-operatively according to center practice. Prednisone should be gradually tapered to no less than 5 mg/day or 10 mg every other day by 3 months post-transplant thereafter until study closure.; 30 to 60 minutes prior to the start of the infusion
Claritin (Loratadine) 10mg by mouth or
Benadryl (Diphenhydramine) 25 or 50 mg by mouth
Intervention MeSH terms: Acetaminophen; Diphenhydramine; Promethazine; Loratadine; Mycophenolic Acid; Prednisone; Methylprednisolone; Methylprednisolone Hemisuccinate; Infliximab; Tacrolimus; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 290.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kidney Transplantation; infliximab; Tissue Donors; Remicade; Induction Therapy; Deceased Donor Kidney Transplant Recipients

Summary:

      During transplant surgery, there is a period of time when a donated kidney is removed from a
      donor's body and stored until the time of the transplant surgery. The storage procedure
      results in buildup of various proteins within the kidney that can injure the donated kidney
      after it is transplanted. One of these proteins is tumor necrosis factor-alpha (TNF-alpha).

      The purpose of this study is to evaluate whether taking infliximab, which blocks tumor
      necrosis factor alpha (TNF-alpha), just prior to transplant surgery, along with usual
      transplant medicines will protect the donated kidney from damage caused by TNF-alpha and help
      keep the transplanted kidney healthy for a longer period of time.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult (>18 years of age) male and female recipients (all races and ethnicities)

          2. Subject must be able to understand and provide consent

          3. Recipients of deceased donor kidney transplants (including re-transplants)

          4. Negative crossmatch, actual or virtual, or a PRA of 0% on historic and current sera as
             determined by each participating study center

          5. Donor kidneys from deceased donors and donors after cardiac death (DCD) with Kidney
             Donor Profile Indices (KDPI) ranging from ≥20 to <95

          6. Female participants of childbearing potential must have a negative pregnancy test upon
             study entry

          7. Subjects must have a negative test result for latent tuberculosis (TB) infection (PPD,
             QuantiFERON, ELISPOT):

               -  Subjects who have a negative test result for latent TB infection within 1 year of
                  transplant date are eligible for enrollment and no further action is required

               -  Subjects who have a negative test for latent TB infection that is greater than 1
                  year old are eligible for enrollment but are required to have a repeat test prior
                  to transplantation.

        Exclusion Criteria:

          1. Inability or unwillingness of a participant to give written informed consent or comply
             with study protocol

          2. Recipients of living donor transplants

          3. Presence of other transplanted solid organ (heart, lung, liver, pancreas, small
             intestines) or co-transplanted organ

          4. Human immunodeficiency virus positive (HIV+) recipients

          5. Epstein-Barr virus Immunoglobulin G (EBV IgG) negative recipients

          6. Hepatitis B surface antigen positive kidney transplant recipients

          7. Hepatitis B core antibody positive kidney transplant recipients

          8. Hepatitis B negative kidney transplant recipients that receive transplants from
             Hepatitis B core antibody positive donor

          9. Hepatitis C Virus positive (HCV+) patients who are either untreated or have failed to
             demonstrate sustained viral remission for more than 12 months after anti-viral
             treatment

         10. Recipients with a previous history of active TB

         11. Recipients with a positive test for latent TB infection (PPD, QuantiFERON, ELISPOT),
             regardless of previous therapy

         12. Any severe infection at the time of transplantation.

             --Note: Severe infection determination will be made by the local site investigator.

         13. Severe congestive heart failure (NYHA functional class III or higher)

         14. Subjects with a known hypersensitivity to any murine/ mouse proteins

         15. Subjects with any history of receiving any anti-tumor necrosis factor (anti- TNF)
             products

         16. Subjects in whom rabbit anti-thymocyte globulin (Thymoglobulin®) or infliximab might
             not be tolerated

         17. Subjects with a white blood cell count less than 3000/mm^3

         18. Subjects with a platelet count less than 100,000/mm^3

         19. Subjects with systolic blood pressure <100 mm/Hg

         20. Subjects with symptomatic orthostatic hypotension or currently requiring Midodrine for
             blood pressure support

         21. Subjects from, or who have traveled, to endemic areas with a history of active
             histoplasmosis or, with a chest x-ray consistent with previous active histoplasmosis
             (no serological testing required) :

             --Endemic regions determined by site based on local standard of care.

         22. Subjects currently or formerly residing in regions of the United States that are
             highly endemic for coccidioidomycosis, and who have a positive serologic test for
             coccidioidomycosis:

             --Endemic regions determined by site based on local standard of care.

         23. Recipients are excluded if the local site decides to treat the recipient with
             fluconazole because of diagnosis or suspicion of fungal infection the donor

         24. Subjects that receive IVIG treatment within 3 months of transplant or planned
             intravenous immunoglobulin (IVIG) treatment peri-transplant

         25. Use of an investigational agent within 4-weeks prior to study entry.