Berinert (C1INH) vs Placebo for DGF/IRI

NCT ID: NCT04696146

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-03
• Study Completion Date: 2024-10-31

Brief Summary

This is a Phase I/II double-blind, randomized, placebo-controlled study assessing safety and limited efficacy of 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). 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.

Detailed 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.

Conditions

End Stage Renal Disease; Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Berinert

Berinert 500 units

Group Type: EXPERIMENTAL

Berinert

Intervention Type: DRUG

Intrarenal dose of 500 U of Berinert

Placebo

Normal Saline in identical volume to Berinert

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal Saline placebo

Interventions

Berinert

Intrarenal dose of 500 U of Berinert

Intervention Type: DRUG

Placebo

Normal Saline placebo

Intervention Type: DRUG

Other Intervention Names

C1 Esterase Inhibitor (C1INH); Normal Saline

Eligibility Criteria

Inclusion Criteria

1. Adult men or women (18-70 years of age) who are on chronic dialysis therapy and acceptable candidates for receipt of a kidney transplant.

2. Recipients who are ABO compatible with donor allograft

3. Understand and sign a written inform consent prior to any study specific procedure

4. Women of childbearing potential must have a negative pregnancy test prior to randomization, and must be on an acceptable form of birth control.

5. . AND one of the below criteria:

a)Recipients of kidney allograft from KDPI >80 donors b)Recipients of kidney allograft from DCD donors c)Recipients of kidney allograft with CIT > 24 hours d)Recipients of kidney allograft from donor on HD/CRRT prior to death/procurement e)Recipients of kidney allograft with donor terminal creatinine SCr ≥3.0 mg/dL f)Patient risk a total risk index score of >/=3

Exclusion Criteria

1. Patients with a known pro-thrombotic disorder. (eg. Factor V Leiden)

2. Patients with a history of thrombosis or hypercoagulable state, excluding access clotting.

3. Patients with a history of administration of C1INH containing products or recombinant C1INH within 15 days prior to study entry.

4. Patients with a known hypersensitivity to treatment with C1INH.

5. Patients with an abnormal coagulation function. (INR>2, PTT> 50, PLT<60,000)who are not on anti-coagulation.

6. Patients with known active presence of malignancies.

7. Patients who arePCR positive for Hep B, Hep C, or HIV.

8. Recipients of pre-emptive kidney transplantation.

9. All zero mismatch kidneys.

10. Recipients of multi-organ transplants. (kidney and any other organ)

11. Recipients of kidney allograft that was on pump preservation for any period prior to transplantation.

12. Recipients of kidney allograft from a living donor.13)Female subjects who are pregnant or lactating.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

OneLegacy Foundation

UNKNOWN

Sponsor Role: collaborator

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Stanley Jordan, MD

Director of Nephrology and Transplant Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cedars Sinai Medical Center

Los Angeles, California, United States

Countries

United States

References

Huang E, Ammerman N, Vo A, Hou J, Kumar S, Badash N, Falk B, Hernando K, Gillespie M, Kim IK, Lim K, Najjar R, Peng A, Shin B, Steggerda JA, Todo T, Brennan TV, Voidonikolas G, Wisel SA, Heeger PS, Jordan SC. Back-table intra-arterial administration of C1 esterase inhibitor to deceased donor kidney allografts improves posttransplant allograft function: Results of a randomized double-blind placebo-controlled clinical trial. Am J Transplant. 2025 Sep;25(9):1926-1939. doi: 10.1016/j.ajt.2025.05.003. Epub 2025 May 9.

Reference Type: DERIVED

PMID: 40349965 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

469

Identifier Type: -

Identifier Source: org_study_id