Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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):
  8. 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
  9. 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.
  13. -Note: Severe infection determination will be made by the local site investigator.
  14. Severe congestive heart failure (NYHA functional class III or higher)
  15. Subjects with a known hypersensitivity to any murine/ mouse proteins
  16. Subjects with any history of receiving any anti-tumor necrosis factor (anti- TNF) products
  17. Subjects in whom rabbit anti-thymocyte globulin (Thymoglobulin®) or infliximab might not be tolerated
  18. Subjects with a white blood cell count less than 3000/mm^3
  19. Subjects with a platelet count less than 100,000/mm^3
  20. Subjects with systolic blood pressure <100 mm/Hg
  21. Subjects with symptomatic orthostatic hypotension or currently requiring Midodrine for blood pressure support
  22. 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) :
  23. -Endemic regions determined by site based on local standard of care.
  24. 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:
  25. -Endemic regions determined by site based on local standard of care.
  26. Recipients are excluded if the local site decides to treat the recipient with fluconazole because of diagnosis or suspicion of fungal infection the donor
  27. Subjects that receive IVIG treatment within 3 months of transplant or planned intravenous immunoglobulin (IVIG) treatment peri-transplant
  28. Use of an investigational agent within 4-weeks prior to study entry.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Experimental Arm
rATG is co-administered with anti-TNFa (infliximab/Remicade®) plus maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
  • Biological: Infliximab
    A single dose, of 3mg/kg infusion
    Other names:
    • Remicade®
  • Drug: Methylprednisolone
    500mg will be Initiated just prior to or at the initiation of transplant surgery and prior to Infliximab and thymoglobulin infusion
    Other names:
    • Solu-Medrol
  • Drug: Mycophenolate Mofetil
    Administered at a target dose of 2000mg daily, as tolerated, until study closure
    Other names:
    • MMF
    • CellCept®
  • Drug: Tacrolimus
    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
    Other names:
    • FK-506
    • FR-900506
    • Prograf®
  • Biological: Thymoglobulin®
    Administered daily for 5 days with the intention of achieving a total dose of 4.5 to 6.0 mg/kg, as tolerated
    Other names:
    • Antithymocyte Globulin [Rabbit]
    • Rabbit ATG
  • Drug: Acetaminophen
    30 to 60 minutes prior to the start of the infusion Tylenol, 600 to 1000mg by mouth or Suppository form
    Other names:
    • Tylenol®
  • Drug: Loratadine
    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
    Other names:
    • Claritin®
  • Drug: Prednisone
    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.
  • Drug: Diphenhydramine
    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
    Other names:
    • Benadryl
Active Comparator
Control group
Rabbit anti-thymocyte globulin (rATG/Thymoglobulin®) plus placebo (Sterile normal saline) induction followed by maintenance therapy with tacrolimus, a mycophenolic acid derivative (either MMF or enteric coated MPA) and prednisone.
  • Drug: Methylprednisolone
    500mg will be Initiated just prior to or at the initiation of transplant surgery and prior to Infliximab and thymoglobulin infusion
    Other names:
    • Solu-Medrol
  • Drug: Mycophenolate Mofetil
    Administered at a target dose of 2000mg daily, as tolerated, until study closure
    Other names:
    • MMF
    • CellCept®
  • Drug: Tacrolimus
    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
    Other names:
    • FK-506
    • FR-900506
    • Prograf®
  • Biological: Thymoglobulin®
    Administered daily for 5 days with the intention of achieving a total dose of 4.5 to 6.0 mg/kg, as tolerated
    Other names:
    • Antithymocyte Globulin [Rabbit]
    • Rabbit ATG
  • Drug: Acetaminophen
    30 to 60 minutes prior to the start of the infusion Tylenol, 600 to 1000mg by mouth or Suppository form
    Other names:
    • Tylenol®
  • Drug: Loratadine
    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
    Other names:
    • Claritin®
  • Biological: Placebo for Infliximab
    A single dose is volume matched to Infliximab (250mL) infusion
  • Drug: Prednisone
    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.
  • Drug: Diphenhydramine
    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
    Other names:
    • Benadryl

Recruiting Locations

University of Maryland
Baltimore, Maryland 21201
Contact:
Amanda Bartosic
410-328-0303
abartosic@som.umaryland.edu

More Details

NCT ID
NCT02495077
Status
Recruiting
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Study Contact

Detailed Description

This is a Phase 2, multicenter, randomized, double blind (masked), placebo-controlled, 2-arm clinical trial of 300 deceased donor kidney transplant recipients. Participants will be randomized (1:1) to the experimental or control arm (150 subjects per arm).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.