Early Conversion From CNI to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function
The purpose of this study is to evaluate the safety and efficacy of conversion from a calcineurin inhibitor (tacrolimus or cyclosporine) immunosuppression therapy to Nulojix® (belatacept) immunosuppression therapy in patients with delayed (DGF) or slow graft function (SGF) following kidney transplantation. Patients at risk for SGF or DGF will be consented at the time of kidney transplantation. On post-op Day 5 the patient will be assessed, if they have developed SGF or DGF they will be randomized to convert to Belatacept or continue on their CNI regimen. Up to 20 subjects who do not develop DGF will be followed as control subjects. Seventy randomized subjects will be followed for a total of 14 months with a renal biopsy at Month 12 post transplant.
- Kidneys with slow or delayed graft function are more susceptible to acute and long-term CNI toxicity
- Kidneys converted from calcineurin inhibitor based therapy to belatacept will achieve a more rapid recovery from post-ischemic acute tubular necrosis (ATN) and will have improved 1 year calculated GFR.
Key Secondary Hypotheses:
- Renal Histology: Belatacept converted patients will have a lower chronic allograft damage index (CADI) score and lower interstitial fibrosis and tubular atrophy (IF/TA) score as calculated by Banff criteria at 1 year post- transplant
- Biomarker Analysis: Biomarker analysis (clusterin) measured in serial urine collections can 1) directly assess CNI induced kidney injury and 2) improve the prediction of patients that benefit in early belatacept conversion.
Delayed Graft Function
Drug: Calcineurin Inhibitor
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Trial of Early Conversion From Calcineurin Inhibitors (CNI) to Belatacept in Renal Transplant Recipients With Delayed and Slow Graft Function|
- cGFR [ Time Frame: 12 months ] [ Designated as safety issue: No ]Serum creatinine will be checked at each study visit from which GFR will be calculated. 12 month 4 variable MDRD calculated GFR will be compared between the belatacept conversion group and the calcineurin inhibitor group.
- Renal Histology [ Time Frame: 12 months ] [ Designated as safety issue: No ]Chronic Allograft Damage Index (CADI) and Interstitial Fibrosis/Tubular Atrophy (IFTA) renal pathology scores will be assessed by a local pathologist. CADI and IF/TA will be recorded at baseline (reperfusion biopsy) and at the 1 year protocol biopsy. The average progression of CADI and IF/TA will be compared in both groups and the average absolute CADI and IF/TA scores will be compared in both groups at 1 year post transplant.
- Biomarker profile [ Time Frame: 12 months ] [ Designated as safety issue: No ]The results of urine biomarkers (clusterin) will be correlated with the development of the primary and secondary endpoints in both groups. In this manner the investigators will be able to understand which genes/proteins are primarily altered by injury and assess how belatacept affects this process.
- Duration of Delayed (or slow) Graft Function [ Time Frame: 12 months ] [ Designated as safety issue: No ]The average duration of DGF/SGF will be compared in both belatacept and CNI groups
- Incidence of Acute Rejection [ Time Frame: 12 months ] [ Designated as safety issue: No ]Acute rejection by month 12 will be assessed by a local pathologist using the Banff 97 working classification of kidney transplant pathology. All biopsies will be interpreted locally for purposes of the study.
- New Onset Diabetes [ Time Frame: 12 months ] [ Designated as safety issue: No ]Subjects will be evaluated for post-transplant diabetes at visits after week 4.
- Blood Pressure Control [ Time Frame: 12 months ] [ Designated as safety issue: No ]Subjects are to be evaluated at each clinic visit to assess the need for adjustment of antihypertensive medication in order to achieve a BP of < 130/80 mmHg. Average systolic and diastolic blood pressure in both groups at Month 12, number of antihypertensive medications and change in intensity of hypertension treatment will be observed.
- Dyslipidemia [ Time Frame: 12 months ] [ Designated as safety issue: No ]Cholesterol levels in both groups, number of patients on dyslipidemic therapy at month 12 and change in intensity of dyslipidemia therapy will be observed
- Graft Survival [ Time Frame: 12 Months ] [ Designated as safety issue: No ]Graft survival will be observed in both groups and compared at 12 months post-transplant
- Patient survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]Patient survival will be observed in both groups and compared at 12 months post-transplant
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Subjects will be converted from standard of care CNI therapy to Belatacept 10 mg/kg IV on post renal transplant Day 7 (+/- 3 days). As suggested in the package insert for de novo dosing, further dosing of belatacept will be given as 10 mg/kg IV at weeks 2, 4, 8 and 12 then 5 mg/kg at week 16 and then every 4 weeks (+/- 5 days) through week 52. CNI will be stopped during the first belatacept infusion.
Other Name: Nulojix
Active Comparator: Calcineurin Inhibitor
Patients randomized to this arm will remain on the current CNI as prescribed by post-transplant standard of care therapy.
Drug: Calcineurin Inhibitor
Other Name: Prograf, Tacrolimus, Cyclosporine
Please refer to this study by its ClinicalTrials.gov identifier: NCT01837043
|Contact: Vinay Nair, D.O.||212-659-8086||Vinay.Nair@mountsinai.org|
|Contact: Brandy M Haydel, CCRC||212-241-0255||Brandy.Haydel@mountsinai.org|
|United States, New York|
|Mount Sinai School of Medicine Recanati/Miller Transplantation Institute||Recruiting|
|New York, New York, United States, 10029|
|Contact: Vinay Nair, D.O. 212-659-8086 Vinay.Nair@mountsinai.org|
|Contact: Brandy Haydel, CCRC 212-241-0255 Brandy.Haydel@mountsinai.org|
|Principal Investigator: Vinay Nair, D.O.|
|Sub-Investigator: Sander Florman, MD|
|Sub-Investigator: Peter Heeger, MD|
|Sub-Investigator: Barbara Murphy, MD|
|Principal Investigator:||Vinay Nair, D.O.||Mount Sinai School of Medicine|