The purpose of this trial is to learn if Belatacept is effective and safe as a first line of immunosuppression treatment in patients undergoing a renal transplant where the donor kidney is obtained in patients with extended criteria.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
595
tablet, oral, 1st month target: 150-300 ng/mL, after 1st month target: 100-250 ng/mL, daily, 36 months, 100-250 ng/mL, daily, 84 months
solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 8 and 12, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months months, 5 mg/kg every 4 weeks, q 4 weeks, 84 months
solution, IV, 10mg/kg: Days 1 and 5, Weeks 2, 4, 6, 8, 10,12, 16, 20, and 24, then 5 mg/kg every 4 weeks, q 4 weeks, 36 months, 5 mg/kg every 4 weeks, q 4 weeks, 84 months
Percentage of Participants Who Survived With a Graft at 12 Months Post-Transplant
Participant and graft survival at 12 months was summarized within each treatment group. Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss was defined as a sustained level of serum creatinine ≥ 6.0 mg/dL (530 μmol/L) as determined by central laboratory for ≥4 weeks or 56 or more consecutive days of dialysis.
Time frame: Month 12 post-transplant
Percentage of Participants With a Measured Glomerular Filtration Rate (GFR) <60 mL/Min Per 1.73 m^2 at Month 12 or a Decrease in Measured GFR >=10 mL/Min Per 1.73 m^2 From Month 3 to Month 12
GFR was assessed using a true measure of glomerular filtration via non-radiolabeled iothalamate clearance test using a validated procedure.
Time frame: From Month 3 to Month 12
Measured Glomerular Filtration Rate (GFR) by Month 12 and 24
GFR was assessed using a true measure of glomerular filtration via nonradiolabeled iothalamate clearance test using a validated procedure. Missing measured GFR assessments were imputed. Here, 'n' signifies the number of evaluable participants for the reporting arm at the given time point. Missing measured GFR assessments were imputed to a GFR of zero.
Time frame: At Month 12 and Month 24
Percentage of Participants With Chronic Allograft Nephropathy (CAN) at Month 12
Biopsy-proven CAN was determined by a blinded central histopathologist using the Banff 97 working classification of kidney transplant pathology. Onset of CAN was determined by the biopsy date when it was observed. Participants were considered as having CAN at 12 months if: CAN observed in a biopsy either prior to 12 months (including baseline biopsy) or first post 12 months biopsy; Participant had graft loss during the first year post transplant; no biopsy available post 12 months and CAN not observed in biopsies prior to 12 months; no biopsy available either prior to or post 12 months; and the measured glomerular filtration rate from Month 3 to Month 12 decreases at least 10 mL/min/1.73m\^2. All other participants with missing 12 month biopsy were considered having no CAN observed at 12 months.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University Of Alabama At Birmingham
Birmingham, Alabama, United States
Ucla Kidney & Kidney-Pancreas Transplant Research Office
Los Angeles, California, United States
National Institute Of Transplantation
Los Angeles, California, United States
Sharp Memorial Hospital
San Diego, California, United States
University Of California San Francisco Medical Center
San Francisco, California, United States
University Of Colorado Health Sciences Center
Aurora, Colorado, United States
Yale University School Of Medicine
New Haven, Connecticut, United States
Lifelink Healthcare Institute
Tampa, Florida, United States
Piedmont Transplant Institute
Atlanta, Georgia, United States
Emory University Hospital
Atlanta, Georgia, United States
...and 69 more locations
Time frame: At Month 12
Percentage of Participants Who Survived With a Graft at 24 and 36 Months Post-Transplant
Participant and graft survival at 12 months was summarized within each treatment group. Graft loss was defined as either functional loss or physical loss (nephrectomy). Functional loss will be defined as a sustained level of serum creatinine ≥ 6.0 mg/dL (530 μmol/L) as determined by central laboratory for ≥ 4 weeks or 56 or more consecutive days of dialysis.
Time frame: Month 24 and Month 36 post-transplant
Calculated Glomerular Filtration Rate (GFR) at 6, 12, 24, 36 and 84 Months
GFR was assessed using a true measure of glomerular filtration via nonradiolabeled iothalamate clearance test using a validated procedure. Missing measured GFR assessments were imputed. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Months 6, 12, 24, 36 and 84
Change in Calculated GFR at Months 12, 24, 36 and 84
GFR was assessed using a true measure of glomerular filtration via nonradiolabeled iothalamate clearance test using a validated procedure. Missing measured GFR assessments were imputed. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Baseline and Months 12, 24, 36 and 84
Number of Participants With Anti-Hypertensive Medications Used to Control Hypertension at 12, 24 and 36 Months
Participants were determined to have hypertension at a particular time point if standardized systolic blood pressure ≥ 130 mm Hg or standardized diastolic blood pressure ≥ 80 mm Hg or participant had received an antihypertensive medication(s) for hypertension. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Baseline and Months 12, 24 and 36
Percentage of Subjects Who Used Anti-Hypertensive Medications to Control Hypertension at Months 12, 24 and 36
Participants were determined to have hypertension at a particular time point if standardized systolic blood pressure ≥ 130 mm Hg or standardized diastolic blood pressure ≥ 80 mm Hg or subject had received an anti-hypertensive medication(s) for hypertension. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Months 12, 24 and 36
Percentage of Participants With New Onset Diabetes Mellitus (NODM) at 12, 24 and 36 Months.
NODM was defined as participant who did not have diabetes prior to randomization. Participants were determined for NODM if the participant received an antidiabetic medication for a duration of at least 30 days, or at least two fasting plasma glucose (FPG) tests indicate that FPG is ≥ 126 mg/dL (7.0 mmol/L).
Time frame: Months 12, 24 and 36
Systolic and Diastolic Blood Pressure (BP) at 12, 24 and 36 Months
Participants were determined to have hypertension at a particular time point if standardized systolic blood pressure ≥ 130 mm Hg or standardized diastolic blood pressure ≥ 80 mm Hg or participant had received an anti-hypertensive medication(s) for hypertension. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Months 12, 24 and 36
Mean Framingham Risk Score From Baseline to Months 12, 24 and 36
The risk score was calculated based on the total points from six variables: Age, Level of LDL-cholesterol, Level of HDL-cholesterol, Presence and severity of systolic or diastolic hypertension, Presence or absence of a history of diabetes mellitus and Presence or absence of a history recent cigarette smoking. Total scores can range from \<-3 to \>14, which translate to a 1% to 56% risk of developing coronary heart disease in 10 years. Totals in the 4 to 6 point range translate to a 7 to 11% risk and 8 to 10 point range translate to a 18 to 27% risk.
Time frame: Baseline and Months 12, 24 and 36
Percentage of Participants Using Lipid-Lowering Therapy at 12, 24, and 36 Months
Dyslipidemia was defined as triglyceride ≥ 500 mg/dL \[5.65 mmol/L\], low density lipoprotein (LDL) ≥ 100 mg/dL \[2.59 mmol/L\], and non-elevated high density lipoprotein (HDL) ≥ 130 mg/dL \[3.36 mmol/L\]. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Months 12, 24 and 36
Change in Total Cholesterol (TC), Non-HDL, LDL and HDL Cholesterol and Triglycerides at 12, 24 and 36
Dyslipidemia was defined as triglyceride ≥ 500 mg/dL \[5.65 mmol/L\], low density lipoprotein (LDL) ≥ 100 mg/dL \[2.59 mmol/L\], and elevated non-high density lipoprotein (HDL) ≥ 130 mg/dL \[3.36 mmol/L\]. Here 'n' signifies those participants evaluable for this measure at specified time points for each arm, respectively.
Time frame: Months 12, 24 and 36
Percentage of Participants Who Have an Acute Rejection by Months 6, 12, 24, 36 and 84
Acute rejection was defined as central biopsy proven rejection that was either clinically suspected by protocol defined reasons or clinically suspected by other reasons and treated. Clinically suspected acute rejection was defined as an unexplained rise of serum creatinine ≥ 25% from baseline creatinine or an unexplained decreased urine output or fever and graft tenderness or serum creatinine that remains elevated within 14 days post--transplantation and clinical suspicion of acute rejection exists.
Time frame: Months 6, 12, 24, 36 and 84
Number of Participants Using Lymphocyte Depleting Therapy and Steroid-Resistant for Acute Rejection by Months 6, 12, 24, and 36.
Acute rejection was defined as central biopsy proven rejection that was either clinically suspected by protocol defined reasons or clinically suspected by other reasons and treated. Lymphocyte -depletion therapy for treatment of an episode of acute was defined as a participant treated with therapy and provided not treated with steroids earlier while steroid resistant acute rejection was defined as participants initially treated with steroids alone for suspected acute rejection for at least 2 days and then followed by the start of lymphocyte -depletion therapy.
Time frame: Months 6, 12, 24 and 36
Number of Participants Based on Severity of Acute Rejection Based on Banff Grade Level by Months 6, 12, 24, 36 and 84
Acute rejection was defined as central biopsy proven rejection that was either clinically suspected by protocol defined reasons or clinically suspected by other reasons and treated. Clinically suspected acute rejection was defined as an unexplained rise of serum creatinine ≥ 25% from baseline creatinine or an unexplained decreased urine output or fever and graft tenderness or serum creatinine that remains elevated within 14 days post--transplantation and clinical suspicion of acute rejection exists.
Time frame: Months 6, 12, 24, 36 and 84
Mean Changes in Mental Component and Physical Component Health-Related Quality of Life (SF-36) From Baseline to Months 12, 24 and 36
The SF-36 is a 36-item self-administered questionnaire developed to assess health-related quality of life (QOL) and comprises 8 domains, including 4 physical (physical health, bodily pain, physical functioning and physical role limitations) and 4 mental (mental health, vitality, social functioning, and emotional role limitation) subscales. Responses are used to derive physical and mental component summary scores, ranging from 0 to 100, with higher scores indicating better QOL (0=Poorest Health; 100=Best Health). Mean change from baseline = post-baseline value - baseline value; a higher value signifies improvement.
Time frame: Baseline and Months 12, 24 and 36
Number of Participants With Clinically Significant Changes in Vital Signs up to 36 Months
Participants with abnormal blood pressure, body weight and body temperature outside the defined normal range were graded as clinically significant vital signs by the investigator.
Time frame: Day 1 to Month 36
Number of Participants With Laboratory Test Abnormalities up to 36 Months
Participants with laboratory values outside the defined normal range were graded as clinically significant laboratory abnormalities by the investigator. Subjects were analyzed for Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase(AST), Hemoglobin, Platelet Count, Leukocytes, Bilirubin, Creatinine, Calcium, Bicarbonate, Potassium, Magnesium, Sodium, Phosphorus, Albumin, Uric Acid and Protein. Laboratory abnormalities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3. Here 'n' signifies those subjects evaluable for this measure at specified time points for each arm, respectively.
Time frame: Day 1 to Month 36
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Related AEs and SAEs, AEs Leading to Discontinuation and Who Died up to Month 36
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time frame: Day 1 to Month 36
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Related AEs and SAEs, AEs Leading to Discontinuation and Who Died up to Month 84
AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time frame: Day 1 to Month 84
Percentage of Participants With Graft Loss or Death to Month 84
Participant and graft survival at 84 months was summarized within each treatment group.
Time frame: Randomization to date of death, up to 84 months