Berinert (C1INH) vs Placebo for DGF/IRI

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Chronic Kidney Diseases
End Stage Renal Disease

Type

Interventional

Phase

Phase 1Phase 2

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Intraoperative C1INH (500U/kidney) vs. Placebo administered into the graft renal artery 1-2 hours prior to implantation in adult subjects receiving a deceased donor kidney allograft considered high-risk for development of DGF (KDPI>80). Patients will be randomized in a 1:1 mannerMasking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Once eligible patients are identified, consented, and have an acceptable kidney transplant offer, they will be randomized by the Cedars-Sinai Research Pharmacy to receive study drug vs. placebo. Drug and placebo will be prepared by the Cedars-Sinai Research Pharmacy and conveyed to the operating room in a blinded manner. The drug will be administered by the transplant surgeon in the OR in a blinded manner.Primary Purpose: Prevention

Participation Requirements

Age: Between 18 years and 70 years
Gender: Both males and females

Description

Pre-operative, infusion of C1INH into the renal allograft artery 1-2 hours prior to implantation will improve early graft function and reduce the rate of DGF, requirements for dialysis, graft survival and eGFR in patients receiving kidney allografts from high risk deceased donor compared to placebo. Early graft function has a long-term effect on graft survival. Poor early graft function and DGF contributes to decreased short- and long-term patient and graft survival, increased incidence of acute rejection, prolonged hospitalization, and higher costs of transplantation. Although multiple factors contribute to the impaired graft function, ischemia-reperfusion injury (IRI) is the underlying pathophysiology leading to poor early graft function and DGF. A >35% incidence of DGF has remained constant over time despite significant improvements in immunosuppressive strategies and patient management. This may be due to increased use of kidneys from "extended-criteria" and/or non-heart-beating donors, where even greater rates (>60%) of DGF have been reported. More than 94,653 people are currently waiting for a kidney transplant in the United States (UNOS.org 9/30/2019). Of the 19,360 kidney transplants performed in the US in 2018, 20% were from DCD donors and 9% from donors of KDPI>85. The USRDS reports that more than 50% of patients on the waiting list are willing to accept a kidney from an expanded-criteria donor (KDPI >85). This study will seek to expand the use of high KDPI kidneys and reduce wastage by showing improved function after C1INH treatment. Patients who fulfill all I/E criteria will be eligible to be enrolled into Study I Study Group (40 patients): Treatment Arm I - KDPI >80 kidneys will be infused with one intrarenal dose of 500U of Berinert® in OR prior to implantation into the recipient. Control Arm - KDPI >80 kidneys will be administered one intrarenal dose of normal saline (NS) in the OR in a volume identical to the volume of the dose of Berinert® before implantation of kidney into the patient. Drug v. placebo administration will be randomized 1:1. Drug preparation and randomization will be carried out in a blinded fashion by research pharmacist.

Tracking Information

NCT #: NCT04696146
Collaborators: OneLegacy Foundation
Investigators: Not Provided