Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (IMPROVE TRIAL)

Inclusion criteria

• Participant must be able to understand and provide informed consent
• Adults who are on chronic dialysis therapy and are on the wait list for deceased donor kidney transplant
• Recipients who are ABO compatible with donor allograft
• Negative crossmatch and no donor specific anti-HLA antibody (DSA) on most recent pretransplant serum sample as determined by local site
• Female participants of childbearing potential must have a negative pregnancy test upon study entry
• 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
• 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
• 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
• Recipients of kidneys arriving to the transplant center on ex vivo hypothermic machine perfusion pumps are eligible
• 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)
• Anticipated Cold Ischemia Time (CIT) >=12 hours
• Kidney Donor Profile Index (KDPI) 21-95%. For KDPI 21-34% to be eligible, anticipated CIT must be >=24 hours
• Patients with normal coagulation

Exclusion criteria

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• Any prior or concurrent non-renal solid organ, or cellular transplant, or waitlisted for multi-organ transplant. Prior autologous transplant is allowed
• Patients receiving enbloc kidneys
• 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)
• Patients with a known pro-thrombotic disorder
• 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
• Body mass index (BMI) >=40 kg/m^2
• 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
• Patients with a known hypersensitivity to treatment with Berinert
• Patients requiring chronic anti-coagulation or anti-platelet therapy. ASA and NSAIDS are allowed
• 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
• Patients who are positive for Hep B infection (Hepatitis B surface antigen (HBsAg)+); patients with HbcAB+ are eligible if HBV PCR is negative
• Any active infection
• Human immunodeficiency virus (HIV) infection
• Enrollment in another investigational trial
• Recent recipient of any licensed or investigational live attenuated vaccine(s) within 4 weeks of enrollment
• Current or planned use of immunomodulatory agents including but not limited to rituximab, belatacept, eculizumab, JAK inhibitors, anti-TNF agents
• Female participants who are pregnant or lactating
• 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
• History of any stroke (including ischemic, hemorrhagic, or embolic) within the previous 6 months