Kidney Transplant
Conditions
Keywords
Kidney transplant, Deceased donor, Intragraft injection, C1 esterase inhibitor
Brief summary
The purpose of this study is to find out if Berinert can improve kidney function in the first year after transplant and to find out what effects, good or bad, Berinert will have in the kidney recipient. This research study will compare Berinert to placebo. The placebo looks exactly like Berinert but does not contain any active drug. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons. Neither you or the study doctor can choose or know which group is assigned. The primary objective is to test whether intrarenal artery C1 esterase inhibitor (C1INH) injection into the donor kidney prior to transplantation improves kidney function in recipients of high risk, deceased donor kidney transplants as measured by 12-month Estimated Glomerular Filtration Rate (eGFR) Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI)
Interventions
BIOLOGICALBerinert
Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft
OTHERPlacebo for Berinert
Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study is a double-blind, placebo-controlled study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must be able to understand and provide informed consent 2. Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant 3. Recipients who are ABO compatible with donor allograft 4. Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site 5. Female participants of childbearing potential must have a negative pregnancy test upon study entry 6. All participants with reproductive potential must agree to use highly effective contraception for at least 12-moths post-transplant. Oral estrogen containing contraception must not be used during the first 3 months post-transplant 7. Hepatitis C Virus Ab positive participants with negative Hepatitis C virus (HCV) Polymerase chain reaction (PCR) are eligible if they have spontaneously cleared infection or are in sustained virologic remission 8. Hepatitis C Virus negative recipients of a Hepatitis C Virus positive organ are eligible if they will be treated with the intent of inducing a sustained virologic remission 9. Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible 10. Recipients of kidneys that received in situ normothermic regional perfusion in the donor are eligible. Kidneys that received normothermic machine perfusion after organ procurement (ex situ normothermic perfusion) are not eligible (See Exclusion #4) 11. Anticipated Cold Ischemia Time (CIT) \>=12 hours 12. Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be \>=24 hours 13. Patients with normal coagulation
Exclusion criteria
1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol 2. Any prior or concurrent non-renal solid organ, or cellular transplant, or waitlisted for multi-organ transplant. Prior autologous transplant is allowed 3. Patients receiving enbloc kidneys 4. Kidneys that received ex vivo normothermic machine perfusion after procurement. Kidneys that received in situ normotherimic regional perfusion in the donor are eligible (see Inclusion #10) 5. Patients with a known pro-thrombotic disorder 6. Patients with a history of thrombosis or hyper-coagulable state, excluding dialysis access clotting or other superficial vein thrombosis not requiring long-term systemic treatment 7. Body mass index (BMI) \>=40 kg/m\^2 8. Patients with a history of Hereditary Angioedema or use of C1 esterase inhibitor (C1INH) containing products or recombinant C1INH within 15 days prior to study entry 9. Patients with a known hypersensitivity to treatment with Berinert 10. Patients requiring chronic anti-coagulation or anti-platelet therapy. ASA and NSAIDS are allowed 11. Presence of active malignancy or history of malignancy less than 5 years in remission, excluding adequately treated in-situ cervical carcinoma, low grade prostate carcinoma, renal cell carcinoma stage T1N0M0 that has been treated with nephrectomy, or adequately treated basal or squamous cell carcinoma of the skin 12. Patients who are positive for Hep B infection (Hepatitis B surface antigen (HBsAg)+); patients with HbcAB+ are eligible if HBV PCR is negative 13. Any active infection 14. Human immunodeficiency virus (HIV) infection 15. Enrollment in another investigational trial 16. Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment 17. Current or planned use of immunomodulatory agents including but not limited to rituximab, belatacept, eculizumab, JAK inhibitors, anti-TNF agents 18. Female participants who are pregnant or lactating 19. Past or current medical problems, inclusive of mental health and substance abuse concerns, or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study 20. History of any stroke (including ischemic, hemorrhagic, or embolic) within the previous 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference between study arms in renal function | At 12-months post-transplantation | Measured as Estimated Glomerular Filtration Rate Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI) in ml/min/1.73m\^2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison between the treated and control group of the full iBox score | At 12-months post-transplantation | The iBox scoring system is a composite biomarker panel. The full iBox scoring system consists of 4 elements all obtained 1-year post-transplant: a) eGFR (MDRD), b) DSA, c) urinary protein/creatine ratio, and d) histological abnormalities on a surveillance biopsy. |
| Incidence of biopsy proven acute rejection (BPAR) | At 12-months post-transplantation | — |
| Incidence of proteinuria | At 12-months post-transplantation | Measured as spot urine protein/creatinine \>1 g/g |
| Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA) | At 12-months post-transplantation | Defined as the incidence of de novo DSA on standard of care or protocol directed blood draws up to and including the 12-month protocol blood draw. |
| Incidence of Grade 3 or higher infections | At 12-months post-transplantation | — |
| Incidence of Grade 3 or higher intraoperative or postoperative hemorrhage | Within 4 weeks after transplantation | — |
| Incidence of thrombotic or thromboembolic events | Within 4 weeks after transplantation | Excluding superficial thrombophlebitis, catheter-related thrombosis and dialysis access thrombosis |
| Incidence of T cell mediated rejection (TCMR) that is steroid resistant | At 12-months post-transplantation | — |
| Incidence of TCMR that is BANFF grade 2 or higher | At 12-months post-transplantation | — |
| Incidence of antibody mediated rejection (ABMR) | At 12-months post-transplantation | — |
| Incidence of death | At 12-months post-transplantation | — |
| Incidence of Graft loss (including primary non function) | At 12-months post-transplantation | — |
Countries
United States
Contacts
STUDY_CHAIRPeter S Heeger, MD
Cedars-Sinai Medical Center
STUDY_CHAIRSindhu Chandran, MBBS, MD
Cedars-Sinai Medical Center
STUDY_CHAIRStanley Jordan, MD
Cedars-Sinai Medical Center
Outcome results
None listed