Effects of Inhibiting Early Inflammation in Kidney Transplant Patients
- Conditions
- Kidney Transplant
- Interventions
- Biological: InfliximabBiological: Thymoglobulin®Biological: Placebo for Infliximab
- Registration Number
- NCT02495077
- Brief 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.
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 290
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Adult (>18 years of age) male and female recipients (all races and ethnicities)
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Subject must be able to understand and provide consent
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Recipients of deceased donor kidney transplants (including re-transplants)
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Negative crossmatch, actual or virtual, or a PRA of 0% on historic and current sera as determined by each participating study center
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Donor kidneys from deceased donors and donors after cardiac death (DCD) with Kidney Donor Profile Indices (KDPI) ranging from ≥20 to <95
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Female participants of childbearing potential must have a negative pregnancy test upon study entry
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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.
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Inability or unwillingness of a participant to give written informed consent or comply with study protocol
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Recipients of living donor transplants
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Presence of other transplanted solid organ (heart, lung, liver, pancreas, small intestines) or co-transplanted organ
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Human immunodeficiency virus positive (HIV+) recipients
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Epstein-Barr virus Immunoglobulin G (EBV IgG) negative recipients
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Hepatitis B surface antigen positive kidney transplant recipients
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Hepatitis B core antibody positive kidney transplant recipients
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Hepatitis B negative kidney transplant recipients that receive transplants from Hepatitis B core antibody positive donor
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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
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Recipients with a previous history of active TB
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Recipients with a positive test for latent TB infection (PPD, QuantiFERON, ELISPOT), regardless of previous therapy
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Any severe infection at the time of transplantation.
--Note: Severe infection determination will be made by the local site investigator.
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Severe congestive heart failure (NYHA functional class III or higher)
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Subjects with a known hypersensitivity to any murine/ mouse proteins
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Subjects with any history of receiving any anti-tumor necrosis factor (anti- TNF) products
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Subjects in whom rabbit anti-thymocyte globulin (Thymoglobulin®) or infliximab might not be tolerated
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Subjects with a white blood cell count less than 3000/mm^3
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Subjects with a platelet count less than 100,000/mm^3
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Subjects with systolic blood pressure <100 mm/Hg
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Subjects with symptomatic orthostatic hypotension or currently requiring Midodrine for blood pressure support
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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.
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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.
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Recipients are excluded if the local site decides to treat the recipient with fluconazole because of diagnosis or suspicion of fungal infection the donor
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Subjects that receive IVIG treatment within 3 months of transplant or planned intravenous immunoglobulin (IVIG) treatment peri-transplant
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Use of an investigational agent within 4-weeks prior to study entry.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Thymoglobulin® 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. Experimental Infliximab 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. Control Placebo for Infliximab 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. Control Thymoglobulin® 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. Experimental Methylprednisolone 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. Experimental Tacrolimus 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. Experimental Mycophenolate Mofetil 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. Experimental Loratadine 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. Experimental Acetaminophen 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. Experimental Prednisone 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. Experimental Diphenhydramine 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. Control Mycophenolate Mofetil 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. Control Acetaminophen 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. Control Tacrolimus 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. Control Diphenhydramine 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. Control Loratadine 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. Control Prednisone 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. Control Methylprednisolone 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.
- Primary Outcome Measures
Name Time Method The Difference Between the Mean eGFR (Modified MDRD) in the Experimental vs. Control Groups. 24-Month post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. eGFR values from months 1, 3, 6, 12, 18, and 24 were used to generate an estimate of the month 24 eGFR for each treatment group.
- Secondary Outcome Measures
Name Time Method Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) 6 month post-transplantation Acute cellular rejection was defined based on central lab pathology interpretation using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to IA with or without clinical symptoms within 6 months of transplant were determined to have met the endpoint. Severity is graded as IA, IB, IIA, IIB, or III, with IA being the mildest form of cellular rejection and III being the most severe form of cellular rejection.Criteria include: IA-significant interstitial infiltration and foci of moderate tubulitis; IB-significant interstitial infiltration and foci of severe tubulitis; IIA-mild to moderate intimal arteritis; IIB-severe intimal arteritis; III-transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) or Borderline Rejection 24 months post-transplantation Acute cellular rejection was defined based on central lab pathology interpretation using the Banff 2007 criteria. Participants with a Banff grade of borderline or greater than or equal to IA with or without clinical symptoms within 24 months of transplant were determined to have met the endpoint. Severity is graded as Borderline, IA, IB, IIA, IIB, or III, with borderline representing possible cellular rejection, IA being the mildest form of cellular rejection, and III being the most severe form of cellular rejection. Criteria include: Borderline-no intimal arteritis is present but foci of mild tubulitis; IA-significant interstitial infiltration and foci of moderate tubulitis; IB-significant interstitial infiltration and foci of severe tubulitis; IIA-mild to moderate intimal arteritis; IIB-severe intimal arteritis; III-transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection (AMR). 24 months post-transplantation Antibody mediated rejection (AMR) was defined based on central lab pathology interpretation using the Banff 2013 criteria. Participants with a Banff finding of AMR within 24 months of transplant were determined to have met the endpoint. AMR is classified as acute/active, chronic/active, or C4d staining positive. Criteria include: acute/active-histologic evidence of acute tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of donor-specific antibodies (DSAs); chronic/active-morphologic evidence of chronic tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of DSAs; C4d staining positive-linear C4d staining in peritubular capillaries, glomerulitis=0, peritubular capillary=0, chronic glomerulopathy=0, no acute cell-mediated rejection or borderline changes.
Change in eGFR Between 3 Months and 24 Months as Measured by MDRD 3 months and 24 months post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. The change in eGFR between months 3 and 24 was calculated as the month 24 eGFR minus the month 3 eGFR for each participant. A window of +/- 14 days was used for month 3 and +/- 1 month was used for month 24.
Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR). 24 months post-transplantation Acute cellular rejection was defined based on central lab pathology interpretation using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to IA with or without clinical symptoms within 24 months of transplant were determined to have met the endpoint. Severity is graded as IA, IB, IIA, IIB, or III, with IA being the mildest form of cellular rejection and III being the most severe form of cellular rejection. Criteria include: IA-significant interstitial infiltration and foci of moderate tubulitis; IB-significant interstitial infiltration and foci of severe tubulitis; IIA-mild to moderate intimal arteritis; IIB-severe intimal arteritis; III-transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
BANFF Grades of First Acute Cellular Rejections (ACR). 6 month post-transplantation Acute cellular rejection was defined based on central lab pathology interpretation using the Banff 2007 criteria. Participants with a Banff grade of greater than or equal to IA with or without clinical symptoms within 6 months of transplant were determined to have met the endpoint. Severity is graded as IA, IB, IIA, IIB, or III, with IA being the mildest form of cellular rejection and III being the most severe form of cellular rejection.Criteria include: IA-significant interstitial infiltration and foci of moderate tubulitis; IB-significant interstitial infiltration and foci of severe tubulitis; IIA-mild to moderate intimal arteritis; IIB-severe intimal arteritis; III-transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
Percent of Participants With Biopsy Proven Acute Cellular Rejection (BPAR) or Borderline Rejection. 6 months post-transplantation Acute cellular rejection was defined based on central lab pathology interpretation using the Banff 2007 criteria. Participants with a Banff grade of borderline or greater than or equal to IA with or without clinical symptoms within 6 months of transplant were determined to have met the endpoint. Severity is graded as Borderline, IA, IB, IIA, IIB, or III, with borderline representing possible cellular rejection, IA being the mildest form of cellular rejection, and III being the most severe form of cellular rejection.Criteria include: Borderline-no intimal arteritis is present but foci of mild tubulitis; IA-significant interstitial infiltration and foci of moderate tubulitis; IB-significant interstitial infiltration and foci of severe tubulitis; IIA-mild to moderate intimal arteritis; IIB-severe intimal arteritis; III-transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection AMR or Suspicious for AMR. 24 months post-transplantation Antibody mediated rejection (AMR) was defined based on central lab pathology interpretation using the Banff 2013 criteria. Participants with a Banff finding of AMR or suspicious for AMR within 24 months of transplant were determined to have met the endpoint. AMR is classified as acute/active, chronic/active, C4d staining positive, or suspicious. Criteria include: acute/active-histologic evidence of acute tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of donor-specific antibodies (DSAs); chronic/active-morphologic evidence of chronic tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of DSAs; C4d staining positive-linear C4d staining in peritubular capillaries, glomerulitis=0, peritubular capillary=0, chronic glomerulopathy=0, no acute cell-mediated rejection or borderline changes; suspicious-when 2 of 3 factors for acute/active are present
Percent of Participants With BANFF Chronicity Scores > or Equal 2 on the 24 Month Biopsy. 24 months post-transplantation The Banff 2013 classification involves scoring numerous characteristics of renal biopsy specimens. The ci (interstitial fibrosis) and ct (tubular atrophy) scores are two such characteristics. The scores can take values of 0, 1, 2, or 3 for each characteristic (ci and ct), indicating increasing severity of disease as the scores increase. Participants are considered to have met this endpoint if their ci + ct score on the 24 month biopsy summed to be \> or equal to 2.
Change in BANFF Chronicity Scores Between Implantation and the 24 Month Biopsy. 24 months post-transplantation The Banff 2013 classification involves scoring numerous characteristics of renal biopsy specimens. The ci (interstitial fibrosis) and ct (tubular atrophy) scores are two such characteristics. The scores can take values of 0, 1, 2, or 3 for each characteristic (ci and ct), indicating increasing severity of disease as the scores increase. For this endpoint, the sum of ci+ct scores from the implantation biopsy was subtracted from the sum of the ci+ct scores from the month 24 biopsy and the difference between the two time points was classified as 0, 1, 2, or 3+. Higher values of this difference indicate more severe disease.
Number of Dialysis Sessions. 8 weeks post-transplantation The number of dialysis sessions a person had during their first 8 weeks post-transplant was used for this endpoint.
Percent of Participants With Locally Treated Rejection, Defined as Treatment Administered for Rejection Based on Clinical Signs or Biopsy Findings. 24 months post-transplantation Biopsies were read by the local pathologist at the hospital where the participant was a patient. These local reads informed clinical care for the participant, which may or may not include prescribing/administering medication to the participant to help with clinical concerns or findings noted on a biopsy. Participants were considered to have met this endpoint if they have a report of receiving treatment for clinical or biopsy-proven rejection during the 24 month post-transplant follow-up.
Change in eGFR Between Post-transplant Nadir and 24 Months as Measured by CKD-EPI 6 months and 24 months post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. Post-transplant nadir was defined as the lowest value of eGFR from the first 6 months post-transplant. The change in eGFR between nadir and month 24 was calculated as the month 24 eGFR minus the nadir eGFR for each participant. A window of +/- 21 days was used for month 6 and +/- 1 month was used for month 24.
Change in eGFR Between 6 Months and 24 Months as Measured by CKD-EPI 6 months and 24 months post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. The change in eGFR between months 6 and 24 was calculated as the month 24 eGFR minus the month 6 eGFR for each participant. A window of +/- 21 days was used for month 6 and +/- 1 month was used for month 24.
Duration of Delayed Graft Function (DGF), Defined as Time From Transplantation to the Last Required Dialysis Treatment. First post-transplant dialysis treatment to last post-transplant dialysis treatment Participants are considered to have had DGF if they had at least one dialysis treatment in the first week post-transplant. For this endpoint, duration was calculated as the date of last post-transplant dialysis treatment minus the date of the first post-transplant dialysis treatment.
The Percent of Participants With a Serum Creatinine of More Than 3 mg/dL. Day 5 post-transplantation Serum creatinine (mg/dL) is used to measure kidney function. A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys. This endpoint is ascertaining slow graft function in the immediate days post-transplant. A participant was considered to have met this endpoint if their day 5 serum creatinine was greater than 3 mg/dL.
Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection (AMR) 6 months post-transplantation Antibody mediated rejection (AMR) was defined based on central lab pathology interpretation using the Banff 2013 criteria. Participants with a Banff finding of AMR within 6 months of transplant were determined to have met the endpoint. AMR is classified as acute/active, chronic/active, or C4d staining positive.Criteria include: acute/active-histologic evidence of acute tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of donor-specific antibodies (DSAs); chronic/active-morphologic evidence of chronic tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of DSAs; C4d staining positive-linear C4d staining in peritubular capillaries, glomerulitis=0, peritubular capillary=0, chronic glomerulopathy=0, no acute cell-mediated rejection or borderline changes.
Percent of Participants With Biopsy Proven Acute Antibody Mediated Rejection AMR or Suspicious for AMR 6 months post-transplantation Antibody mediated rejection (AMR) was defined based on central lab pathology interpretation using the Banff 2013 criteria. Participants with a Banff finding of AMR or suspicious for AMR within 6 months of transplant were determined to have met the endpoint. AMR is classified as acute/active, chronic/active, C4d staining positive, or suspicious. Criteria include: acute/active-histologic evidence of acute tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of donor-specific antibodies (DSAs); chronic/active-morphologic evidence of chronic tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of DSAs; C4d staining positive-linear C4d staining in peritubular capillaries, glomerulitis=0, peritubular capillary=0, chronic glomerulopathy=0, no acute cell-mediated rejection or borderline changes; suspicious-when 2 of 3 factors for acute/active are present.
BANFF Grades of First AMR. 6 months post-transplantation Antibody mediated rejection (AMR) was defined based on central lab pathology interpretation using the Banff 2013 criteria. Participants with a Banff finding of AMR within 6 months of transplant were determined to have met the endpoint. AMR is classified as acute/active, chronic/active, or C4d staining positive. Criteria include: acute/active-histologic evidence of acute tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of donor-specific antibodies (DSAs); chronic/active-morphologic evidence of chronic tissue injury, evidence of current/recent antibody interaction with vascular endothelium, and serologic evidence of DSAs; C4d staining positive-linear C4d staining in peritubular capillaries, glomerulitis=0, peritubular capillary=0, chronic glomerulopathy=0, no acute cell-mediated rejection or borderline changes.
Change in eGFR Between 3 Months and 24 Months as Measured by CKD-EPI 3 months and 24 months post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. The change in eGFR between months 3 and 24 was calculated as the month 24 eGFR minus the month 3 eGFR for each participant. A window of +/- 14 days was used for month 3 and +/- 1 month was used for month 24.
Change in eGFR Between Post-transplant Nadir and 24 Months as Measured by MDRD 6 months and 24 months post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. Post-transplant nadir was defined as the lowest value of eGFR from the first 6 months post-transplant. The change in eGFR between nadir and month 24 was calculated as the month 24 eGFR minus the nadir eGFR for each participant. A window of +/- 21 days was used for month 6 and +/- 1 month was used for month 24.
Change in eGFR Between 6 Months and 24 Months as Measured by MDRD 6 months and 24 months post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. The change in eGFR between months 6 and 24 was calculated as the month 24 eGFR minus the month 6 eGFR for each participant. A window of +/- 21 days was used for month 6 and +/- 1 month was used for month 24.
Percent of Participants With Death or Graft Failure. 24 months post-transplantation Participants who died or experienced graft failure were considered to have met this endpoint. Graft failure was defined as the need for post-transplant dialysis for more than 56 days.
Percent of Participants That Required at Least One Dialysis Treatment. 1 week post-transplantation Dialysis within the first week post-transplant is used in the setting of delayed graft function (DGF). Participants are considered to have had DGF if they had at least one dialysis treatment in the first week post-transplant.
eGFR Values as Measured by MDRD Days 30, 60, and 180 post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Modification of Diet in Renal Disease (MDRD) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. eGFR values from day 7 and months 1, 3, 6, 12, 18, and 24 were used to generate an estimate of the eGFR at each time point of interest for each treatment group.
Percent of Participants With Primary Non-Function (PNF), Defined as Dialysis-dependency for More Than 3 Months. Transplantation through at least month 3 up to month 24 Post-transplant dialysis is sometimes required in the setting of kidney transplant. If such dialysis continues for more than 3 months, the participant is considered to have PNF and, as such, meets this endpoint definition.
The Percent of Participants Who Need Dialysis After Week 1. 1 week to 24 months post-transplantation Participants who needed dialysis after the first week post-transplant were considered to have met this endpoint.
Percent of Participants With Mycobacterial or Fungal Infections 24 months post-transplantation Participants were considered to have met this endpoint if they had at least one mycobacterial of fungal infection.
eGFR Values as Measured by CKD-EPI Days 30, 90, and 180 post-transplantation Glomerular filtration rate (GFR) is a measure of kidney function and helps determine the stage of kidney disease. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) equation. A value of 90+ means kidney function is normal. A value between 60 and 89 indicates mildly reduced kidney function, pointing to kidney disease. Values between 30 and 59 indicates moderately reduced kidney function. Values between 15 and 29 indicate severely reduced kidney function. Values below 15 indicate very severe or endstage kidney failure. eGFR values from day 7 and months 1, 3, 6, 12, 18, and 24 were used to generate an estimate of the eGFR at each time point of interest for each treatment group.
Percent of Participants With Only Graft Failure. 24 months post-transplantation Participants who experienced graft failure were considered to have met this endpoint. Graft failure was defined as the need for post-transplant dialysis for more than 56 days.
Days From Transplantation Until Event (ACR, AMR, or Hospitalization for Infection and/or Malignancy) 24 months post-transplantation Participants are considered to have met this endpoint if they experienced biopsy-proven T-cell mediated rejection (ACR) or antibody mediated rejection (AMR) based on central pathology reading or were hospitalized for infection and/or malignancy. For participants who met one or more of these three components, the earliest event date of the three components was used as the time of meeting the endpoint. Participants who did not meet any of the three components were censored at their last date of follow-up. Event (or censor) day was calculated as event (or censor) date minus transplant date.
The Percent of Participants Whose Day 2 Serum CRR Was Less Than 30%. Day 2 post-transplantation Serum creatinine (mg/dL) is used to measure kidney function. A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys. CRR was calculated as the day 1 post-transplant creatinine value minus the day 2 creatinine value divided by the day 1 creatinine value and multiplied by 100, resulting in a percentage. Higher numbers indicate a greater reduction in serum creatinine and, thus, potentially better kidney function. A participant was considered to have met this endpoint if their day 2 serum CRR was less than 30%.
Percent of Participants With de Novo DSA. 24 months post-transplantation Donor specific antibody (DSA) can be formed post-transplant as part of the recipient's alloimmune response to the transplanted organ. DSA was determined by a central laboratory. Participants with newly developed DSA (i.e., de novo) following transplant were considered to have met this endpoint.
Percent of Participants With BK Viremia That Require a Change in Immunosuppression or Anti-viral Treatment as Per Standard of Care at the Site. 24 months post-transplantation Participants were considered to have met this endpoint if they had a reported case of BK viremia that required a change in their existing immunosuppression or the use of anti-viral therapy.
Creatinine Reduction Ratio (CRR), Defined as the First Creatinine on Day 2 Divided by he First Creatinine After Surgery Day 2 post-transplantation Serum creatinine (mg/dL) is used to measure kidney function. A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys. CRR was calculated as the day 1 post-transplant creatinine value minus the day 2 creatinine value divided by the day 1 creatinine value and multiplied by 100, resulting in a percentage. Higher numbers indicate a greater reduction in serum creatinine and, thus, potentially better kidney function.
The Percent of Participants Whose Day 5 Serum CRR Was Less Than 70%. Day 5 post-transplantation Serum creatinine (mg/dL) is used to measure kidney function. A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys. CRR was calculated as the day 1 post-transplant creatinine value minus the day 5 creatinine value divided by the day 1 creatinine value and multiplied by 100, resulting in a percentage. Higher numbers indicate a greater reduction in serum creatinine and, thus, potentially better kidney function. A participant was considered to have met this endpoint if their day 5 serum CRR was less than 70%.
Percent of Participants With Any Infection Requiring Hospitalization or Resulting in Death. 24 months post-transplantation Participants were considered to have met this endpoint if they had an infection that required hospitalization or resulted in death.
Change From Baseline (Immediately After Surgery) in Serum Creatinine. 24, 48 and 72 hours post-transplantation Serum creatinine (mg/dL) is used to measure kidney function. A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys. eGFR values from 24, 48, and 72 hours post-transplant (i.e., days 1, 2, and 3) were used to generate an estimate of the serum creatinine at each time point of interest for each treatment group.
Creatinine Reduction Ratio (CRR), Defined as the First Creatinine on Day 5 Divided by the First Creatinine After Surgery. Day 5 post-transplantation Serum creatinine (mg/dL) is used to measure kidney function. A normal result is 0.7 to 1.3 mg/dL for men and 0.6 to 1.1 mg/dL for women. Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys. CRR was calculated as the day 1 post-transplant creatinine value minus the day 5 creatinine value divided by the day 1 creatinine value and multiplied by 100, resulting in a percentage. Higher numbers indicate a greater reduction in serum creatinine and, thus, potentially better kidney function.
Percent of Participants With CMV Viremia That Require a Change in Immunosuppression or Anti-viral Treatment as Per Standard of Care at the Site 24 months post-transplantation Participants were considered to have met this endpoint if they had a reported case of CMV viremia that required a change in their existing immunosuppression or the use of anti-viral therapy.
Percent of Participants With Malignancy. 24 months post-transplantation Participants were considered to have met this endpoint if they had a reported case of malignancy.
Percent of Participants With Impaired Wound Healing Manifested by Wound Dehiscence, Wound Infection, or Hernia at the Site of the Transplant Incision 24 months post-transplantation Participants were considered to have met this endpoint if they had a reported case of impaired wound healing at the site of the transplant incision manifested by one wound dehiscence, wound infection, or hernia.
Trial Locations
- Locations (15)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Emory University
🇺🇸Atlanta, Georgia, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
University of Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Yale University
🇺🇸New Haven, Connecticut, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States