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

Официальное название

Improving Deceased-Donor Kidney Transplant Outcomes Via a Single Intragraft Injection of C1 Esterase Inhibitor (RTB-021)

Обзор

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)

Вмешательства

• Биопрепарат Berinert
  Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft
• Другое Placebo for Berinert
  Administered as a 10 ml renal artery infusion approximately 1-2 hours before implantation and reperfusion of the allograft

Первичные конечные точки

• Difference between study arms in renal function [Срок оценки: At 12-months post-transplantation]

Вторичные конечные точки (12)

• Comparison between the treated and control group of the full iBox score [Срок оценки: At 12-months post-transplantation]
• Incidence of biopsy proven acute rejection (BPAR) [Срок оценки: At 12-months post-transplantation]
• Incidence of proteinuria [Срок оценки: At 12-months post-transplantation]
• Incidence of de novo donor specific anti-Human Leukocyte Antigen (HLA) antibody (DSA) [Срок оценки: At 12-months post-transplantation]
• Incidence of Grade 3 or higher infections [Срок оценки: At 12-months post-transplantation]
• Incidence of Grade 3 or higher intraoperative or postoperative hemorrhage [Срок оценки: Within 4 weeks after transplantation]
• Incidence of thrombotic or thromboembolic events [Срок оценки: Within 4 weeks after transplantation]
• Incidence of T cell mediated rejection (TCMR) that is steroid resistant [Срок оценки: At 12-months post-transplantation]
• Incidence of TCMR that is BANFF grade 2 or higher [Срок оценки: At 12-months post-transplantation]
• Incidence of antibody mediated rejection (ABMR) [Срок оценки: At 12-months post-transplantation]
• Incidence of death [Срок оценки: At 12-months post-transplantation]
• Incidence of Graft loss (including primary non function) [Срок оценки: At 12-months post-transplantation]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Cedars Sinai Medical Center — Los Angeles
• Northwestern Memorial Hospital — Chicago
• Kansas University Medical Center — Kansas City
• Montefiore Medical Center — The Bronx

Идентификаторы

NCT: NCT06919003 · DAIT RTB-021

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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