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Effects of Inhibiting Early Inflammation in Kidney Transplant Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Clinical Trials in Organ Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02495077
First received: July 6, 2015
Last updated: September 14, 2016
Last verified: September 2016
  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 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 Intervention Phase
Kidney Transplant
Biological: Infliximab
Drug: Methylprednisolone
Drug: Mycophenolate Mofetil
Drug: Tacrolimus
Biological: Thymoglobulin
Drug: Acetaminophen
Drug: Loratadine
Biological: Placebo for Infliximab
Drug: Prednisone
Drug: Diphenhydramine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of Infliximab (Remicade®) Induction Therapy for Deceased Donor Kidney Transplant Recipients (CTOT-19)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • The difference between the mean eGFR (modified MDRD) in the experimental vs. control groups. [ Time Frame: 24-Month post-transplantation ]

Secondary Outcome Measures:
  • Proportion of subjects with biopsy proven acute cellular rejection (BPAR) [ Time Frame: 6 month post-transplantation ]
  • Proportion of subjects with biopsy proven acute cellular rejection (BPAR). [ Time Frame: 2 years post-transplantation ]
  • BANFF grades of first Acute Cellular Rejections (ACR). [ Time Frame: 6 month post-transplantation ]
    Based on BANFF 2007 Scoring Criteria

  • Proportion of subjects with biopsy proven acute cellular rejection (BPAR) or borderline rejection. [ Time Frame: 6 months post-transplantation ]
  • Proportion of subjects with biopsy proven acute cellular rejection (BPAR) or borderline rejection [ Time Frame: 2 years post-transplantation ]
  • Proportion of subjects with biopsy proven acute antibody mediated rejection (AMR) [ Time Frame: 6 months post-transplantation ]
  • Proportion of subjects with biopsy proven acute antibody mediated rejection (AMR). [ Time Frame: 2 years post-transplantation ]
  • Proportion of subjects with biopsy proven acute antibody mediated rejection AMR or suspicious for AMR [ Time Frame: 6 months post-transplantation ]
  • Proportion of subjects with biopsy proven acute antibody mediated rejection AMR or suspicious for AMR. [ Time Frame: 2 years post-transplantation ]
  • BANFF grades of first AMR. [ Time Frame: 6 months post-transplantation ]
  • Proportion of subjects with BANFF chronicity scores > or equal 2. [ Time Frame: 24 month post-transplantation ]
  • Change in BANFF chronicity scores Change Between implantation and 24 month biopsies. [ Time Frame: 24 month post-transplantation ]
  • Change in eGFR between 3 months and 24 months [ Time Frame: 24 month post-transplantation ]
    As measured by both MDRD and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)

  • Change in eGFR between post-transplant nadir and 24 months [ Time Frame: 24 month post-transplantation ]
    As measured by both MDRD and CKD-EPI

  • eGFR Values [ Time Frame: On days 7, 30, 90, and 180 post-transplantation ]
    As measured by both MDRD and CKD-EPI

  • Proportion of subjects with death or graft failure. [ Time Frame: 2 years post-transplantation ]
  • Proportion of subjects with only graft failure. [ Time Frame: 2 years post-transplantation ]
  • Proportion of subjects that required at least one dialysis treatment. [ Time Frame: 1 week post-transplantation ]
  • Number of dialysis sessions. [ Time Frame: 8 weeks post-transplantation ]
  • Duration of delayed graft function (DGF) defined from transplantation to the last required dialysis treatment. [ Time Frame: 2 years post-transplantation ]
  • The incidence of primary non-function (PNF), defined as for dialysis-dependency for more than 3 months. [ Time Frame: 2 years post-transplantation ]
  • Change from baseline (immediately after surgery) in serum creatinine and serum creatinine concentration. [ Time Frame: 24, 48 and 72 hours post-transplantation ]
  • Event (ACR, AMR, or hospitalization for infection and or malignancy) [ Time Frame: 2 years post-transplantation ]
  • Proportion of Slow Graft Function (SGF) [ Time Frame: Day 5 post-transplantation ]
    The proportion of patients with a serum creatinine of more than 3 mg/dL.

  • Ratio of Slow Graft Function (SGF) [ Time Frame: Day 2 and 7 post-transplantation ]
    Creatinine reduction ratio (CRR) defined as the first creatinine on the day divided by the first creatinine after surgery).

  • Proportion of Slow Graft Function (SGF) [ Time Frame: Day 5 post-transplantation ]
    The proportion of patients whose day 5 serum CRR was less than 70%

  • Proportion of Slow Graft Function (SGF) [ Time Frame: Day 2 post-transplantation ]
    The proportion of patients whose day 2 serum CRR was less than 30%

  • Proportion of Slow Graft Function [ Time Frame: 1 week post-transplantation ]
    Proportion of subjects who need dialysis after 1 week.

  • Proportion of subjects with any infection requiring hospitalization or resulting in death. [ Time Frame: 5 years post-transplantation ]
  • Proportion of subjects with Mycobacterial or fungal infections [ Time Frame: 5 years post-transplantation ]
  • Proportion of subjects with CMV viremia require a change in immunosuppression or anti-viral treatment as per standard of care at the site [ Time Frame: 5 years post-transplantation ]
    as per standard of care at the site.

  • Proportion of subjects with BK viremia that require a change in immunosuppression or anti-viral treatment as per standard of care at the site. [ Time Frame: 5 years ]
    as per standard of care at the site.

  • Proportion of subjects with malignancy. [ Time Frame: 5 years post-transplantation ]
  • Proportion of subjects with impaired wound healing manifested by wound dehiscence, wound infection, or hernia at the site of the transplant incision [ Time Frame: 5 years post-transplantation ]

Estimated Enrollment: 300
Study Start Date: September 2015
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Solu-Medrol
Drug: Mycophenolate Mofetil
Administered at a target dose of 2000mg daily, as tolerated, until study closure
Other Names:
  • CellCept
  • MMF
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
  • Prograft
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:
  • Anti-Thymocyte 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 Name: 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 Name: 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 Name: 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 Name: Solu-Medrol
Drug: Mycophenolate Mofetil
Administered at a target dose of 2000mg daily, as tolerated, until study closure
Other Names:
  • CellCept
  • MMF
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
  • Prograft
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:
  • Anti-Thymocyte 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 Name: 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 Name: 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 Name: Benadryl

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject must be able to understand and provide consent
  2. Recipients of deceased donor kidney transplants
  3. Recipients of HLA mismatched kidneys
  4. Recipients who are virtual cross match negative as determined by local HLA lab
  5. Donor kidneys from deceased donors and donors after cardiac death (DCD) with Kidney Donor Profile Indices (KDPI) ranging from >35 to <95
  6. Female participants of childbearing potential must have a negative pregnancy test upon study entry

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 organ or co-transplanted organ
  4. Recipients of kidneys with zero HLA mismatches
  5. HIV+ recipients
  6. EBV negative recipients
  7. Hepatitis B surface antigen positive kidney transplant recipients
  8. Hepatitis B core antibody positive kidney transplant recipients
  9. Hepatitis B negative kidney transplant recipients that receive transplants from Hepatitis B core antibody positive donor
  10. 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
  11. Recipients with a previous history of active TB
  12. Patients with a positive test for TB exposure (PPD, QuantiFERON, ELISPOT) without history of active infection who have NOT completed a full course of INH therapy
  13. Recipients with a positive virtual cross match as determined by the local HLA lab
  14. Any infection at the time of transplantation
  15. Severe congestive heart failure (NYHA functional class III or higher)
  16. Subjects with a known hypersensitivity to any murine/ mouse proteins.
  17. Subjects with any history of receiving any anti-TNF products
  18. Subjects in whom rATG or infliximab might not be tolerated
  19. Subjects with less than 3000/mm^3 WBC
  20. Subjects with less than 100,000/mm^3 platelets counts
  21. Subjects with systolic blood pressure < 100 mm/Hg
  22. Subjects with symptomatic orthostatic hypotension or currently requiring Midodrine for blood pressure support
  23. Subjects from or who have traveled to endemic areas with a history of active histoplasmosis or with a CXR consistent with previous active histoplasmosis (no serological testing required).
  24. Subjects currently or formerly residing in regions of the US that are highly endemic for coccidioidomycosis, and who have a positive serologic test for coccidioidomycosis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02495077

Locations
United States, California
University of California, Los Angeles Not yet recruiting
Los Angeles, California, United States, 90024
Contact: Suphamai Bunnapradist    310-794-8516    bunnapradist@mednet.ucla.edu   
Principal Investigator: Janette Gadzhyan, MD, MS         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Emilio Fernandez    415-353-8380    Emilio.Fernandez@ucsf.edu   
Principal Investigator: Flavio Vincenti, MD         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06511
Contact: Ricarda Tomlin    203-785-2073    ricarda.tomlin@yale.edu   
Principal Investigator: Richard Formica Jr., MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Elizabeth Ferry    404-712-1816    elizabeth.ferry@emoryhealthcare.org   
Principal Investigator: Kenneth Newell, MD, PhD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Jennifer Mawby    734-936-4811    jlmawby@med.umich.edu   
Principal Investigator: Milagros Samaniego-Picota, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Cusanelli Rebecca    314-362-4109    rcusanel@dom.wustl.edu   
Principal Investigator: Daniel Brennan, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Douglas Wilson    212-659-8049    Douglas.Wilson@mountsinai.org   
Principal Investigator: Madhav Menon, MD         
Principal Investigator: Peter Heeger, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44106
Contact: Dianna Sendrey    216-444-0486    sendred2@ccf.org   
Principal Investigator: Emilio Poggio, MD         
University Hospitals of Cleveland Recruiting
Cleveland, Ohio, United States, 44106
Contact: Tracey Lee    216-844-5396    tracey.lee@uhhospitals.org   
Principal Investigator: Donald Hricik, MD         
Canada, Manitoba
University of Manitoba Not yet recruiting
Winnipeg, Manitoba, Canada, R3A 1R9
Contact: Caroline Slivinski    (204) 787-8662    cslivinski@exchange.hsc.mb.ca   
Principal Investigator: Julie Ho, MD         
Principal Investigator: David Rush, MD         
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Clinical Trials in Organ Transplantation
Investigators
Principal Investigator: Peter Heeger, MD Icahn School of Medicine at Mount Sinai
Study Chair: Donald E Hricik, MD University Hospitals Cleveland Medical Center
  More Information

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02495077     History of Changes
Other Study ID Numbers: DAIT CTOT-19
Study First Received: July 6, 2015
Last Updated: September 14, 2016

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Kidney Transplantation
infliximab
Tissue Donors
Remicade
Induction Therapy
Deceased Donor Kidney Transplant Recipients

Additional relevant MeSH terms:
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Tacrolimus
Mycophenolate mofetil
Antilymphocyte Serum
Acetaminophen
Diphenhydramine
Infliximab
Promethazine
Loratadine
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on April 26, 2017