End Stage Renal DiseasePhase 1/2NCT04696146
Berinert (C1INH) vs Placebo for DGF/IRI
A Phase 1/2 study testing Berinert in people with End Stage Renal Disease and Chronic Kidney Diseases, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- End Stage Renal Disease, Chronic Kidney Diseases
- What is being tested?
- Berinert
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2021to 31 Oct 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult men or women (18-70 years of age) who are on chronic dialysis therapy and acceptable candidates for receipt of a kidney transplant.
- Recipients who are ABO compatible with donor allograft
- Understand and sign a written inform consent prior to any study specific procedure
- Women of childbearing potential must have a negative pregnancy test prior to randomization, and must be on an acceptable form of birth control.
- . 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
Who cannot join
- Patients with a known pro-thrombotic disorder. (eg. Factor V Leiden)
- Patients with a history of thrombosis or hypercoagulable state, excluding access clotting.
- Patients with a history of administration of C1INH containing products or recombinant C1INH within 15 days prior to study entry.
- Patients with a known hypersensitivity to treatment with C1INH.
- Patients with an abnormal coagulation function. (INR>2, PTT> 50, PLT<60,000)who are not on anti-coagulation.
- Patients with known active presence of malignancies.
Show all 12Show fewer
- Patients who arePCR positive for Hep B, Hep C, or HIV.
- Recipients of pre-emptive kidney transplantation.
- All zero mismatch kidneys.
- Recipients of multi-organ transplants. (kidney and any other organ)
- Recipients of kidney allograft that was on pump preservation for any period prior to transplantation.
- Recipients of kidney allograft from a living donor.13)Female subjects who are pregnant or lactating.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: A Phase I/II, Double-Blind, Placebo-Controlled Study: Assessing Safety and Efficacy of Preoperative Renal Allograft Infusions of C1 Inhibitor (Berinert®) (Human) (C1INH) vs. Placebo Administration in Recipients of a Renal Allograft From Deceased High Risk Donors and Its Impact on Delayed Graft Function (DGF) and Ischemia/Reperfusion Injury (IRI)
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.
Read the 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
- Being tested
- Berinert, Placebo
- Medical subject headings
- Kidney Failure, Chronic, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerinertDrug
Also called C1 Esterase Inhibitor (C1INH)
Intrarenal dose of 500 U of Berinert
PlaceboDrug
Also called Normal Saline
Normal Saline placebo
| Study group | Role | What they receive |
|---|---|---|
| Berinert | Experimental | Berinert 500 units Receives: Drug: Berinert |
| Placebo | Placebo comparator | Normal Saline in identical volume to Berinert Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Need for Dialysis in the First 30 Days Post-transplant
The percentage of patients enrolled who require at least one session of dialysis in the first 30 days post transplant.
Measured: 30 days
Renal Function 6 Months
eGFR at 6M post-transplant
Measured: 6 months
Graft Survival 6 Months
Number of participants with graft survival at 6 Months
Measured: 6 months
Secondary outcomes (2)
Rejection Episodes at 6 Months
Number of participants with a rejection episodes by day 180
Measured: Month 6
Development of Donor Specific Antibodies (DSA) at 6 Months
Number of participants with Donor Specific Antibodies (DSA) at 6 Months
Measured: Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start3 Mar 2021
- Primary completion31 Jul 2022
- Study completion31 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 manner
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- OneLegacy Foundation
- Responsible party
- Principal investigator, Stanley Jordan, MD, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04696146
- Sponsor's protocol ID
- 469
- Status last verified
- Nov 2024
- First submitted
- 22 Dec 2020
- Last updated
- 4 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Alibrandi S, Clemens A, Li Y, Shufesky WJ, Vo A, Ammerman N, Huang E, Watkins SC, Heeger P, Jordan S, Morelli AE, Chun N. Exosome-primed T cell immunity is facilitated by complement activation. Am J Transplant. 2026 Jan;26(1):52-64. doi: 10.1016/j.ajt.2025.09.011. Epub 2025 Sep 17.
PubMed 40972903Huang 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.
PubMed 40349965
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Double-Blind, Placebo-Controlled Study: Assessing Safety and Efficacy of Preoperative Renal Allograft Infusions of C1 Inhibitor (Berinert®) (Human) (C1INH) vs. Placebo Administration in Recipients of a Renal Allograft From Deceased High Risk Donors and Its Impact on Delayed Graft Function (DGF) and Ischemia/Reperfusion Injury (IRI)
- ClinicalTrials.gov ID
- NCT04696146
- Acronym / sponsor ID
- 469
- Conditions
- End Stage Renal Disease, Chronic Kidney Diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- OneLegacy Foundation
- Study start
- 3 Mar 2021 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Oct 2024 (actual)
- First posted
- 6 Jan 2021 (actual)
- Results
- Posted 29 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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 manner
| Arm | Type | Receives |
|---|---|---|
| Berinert | Experimental | Drug: BerinertBerinert 500 units |
| Placebo | Placebo comparator | Drug: PlaceboNormal Saline in identical volume to Berinert |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult men or women (18-70 years of age) who are on chronic dialysis therapy and acceptable candidates for receipt of a kidney transplant.
- Recipients who are ABO compatible with donor allograft
- Understand and sign a written inform consent prior to any study specific procedure
- Women of childbearing potential must have a negative pregnancy test prior to randomization, and must be on an acceptable form of birth control.
- . AND one of the below criteria:
Key exclusion criteria (12 listed)
- Patients with a known pro-thrombotic disorder. (eg. Factor V Leiden)
- Patients with a history of thrombosis or hypercoagulable state, excluding access clotting.
- Patients with a history of administration of C1INH containing products or recombinant C1INH within 15 days prior to study entry.
- Patients with a known hypersensitivity to treatment with C1INH.
- Patients with an abnormal coagulation function. (INR>2, PTT> 50, PLT<60,000)who are not on anti-coagulation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BerinertAlso: C1 Esterase Inhibitor (C1INH)Intrarenal dose of 500 U of Berinert | Drug | Berinert |
| PlaceboAlso: Normal SalineNormal Saline placebo | Drug | Placebo |
Primary outcome
Need for Dialysis in the First 30 Days Post-transplant
Time frame: 30 days
The percentage of patients enrolled who require at least one session of dialysis in the first 30 days post transplant.
Renal Function 6 Months
Time frame: 6 months
eGFR at 6M post-transplant
Graft Survival 6 Months
Time frame: 6 months
Number of participants with graft survival at 6 Months
2 secondary outcomes
Rejection Episodes at 6 Months
Time frame: Month 6
Development of Donor Specific Antibodies (DSA) at 6 Months
Time frame: Month 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40972903Alibrandi S, Clemens A, Li Y, Shufesky WJ, Vo A, Ammerman N, Huang E, Watkins SC, Heeger P, Jordan S, Morelli AE, Chun N. Exosome-primed T cell immunity is facilitated by complement activation. Am J Transplant. 2026 Jan;26(1):52-64. doi: 10.1016/j.ajt.2025.09.011. Epub 2025 Sep 17.
- Derived from this study: PubMed 40349965Huang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Berinert in people with End Stage Renal Disease and Chronic Kidney Diseases, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Need for Dialysis in the First 30 Days Post-transplant (time frame: 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04696146, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.