Clinical trial NCT05743751: Normothermic Machine Perfusion (NMP) Versus Hypothermic Machine Perfusion (HMP) in Human Kidney Transplantation
Official title: Prospective Randomized Controlled Study Normothermic Pulse Perfusion Comparing and Hypothermic Machine Perfusion in Margin Deceased Donor Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Kidney Transplantation
Keywords: Kidney Transplantation
Normothermic Machine Perfusion
Hypothermic Machine Perfusion
Lead sponsor: China-Japan Friendship Hospital
Sponsor class: OTHER
First posted: 2023-02-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Due to the rising incidence of renal failure and the improvement of organ transplantation technology, the shortage of donor organs has become one of the main problems limiting the development of kidney transplantation. Marginal donor is one of the important ways to extend the donor pool. Normothermic mechanical perfusion (NMP) is a new generation of organ preservation technology, which can maintain the blood supply and at the same time evaluate the marginal kidney function during the organ preservation. However, the clinical effect has not been proved. Hypothermic Machine Perfusion (HMP) is the mainstream organ perfusion technology. This study aims to compare the effectiveness of NMP with the HMP.

Detailed description: The main purpose of the study is to improve the utilization rate of marginal donors through normothermic perfusion, and reduce the incidence of infection, severe rejection and even graft failure caused by implantation of marginal donors. This study aims at the following aspects:

1. To compare the effects of two methods and perfusion parameters on the quality of marginal donors: normal temperature pulse perfusion and low temperature mechanical perfusion;
2. Explore the methods of evaluating the function of donor organs;
3. Exploring the effects of different mechanical perfusion methods and perfusion conditions on marginal donors;
4. The effect of broad-spectrum antibiotics on improving donor infection through different administration routes and different drug doses during perfusion and preservation.

A single-center prospective randomized controlled study was used to compare the prognosis of renal transplantation between 50 patients with normothermic pulse perfusion and 50 patients with hypothermic mechanical perfusion who were enrolled in our hospital for allograft kidney transplantation.

Assessment factors:

1. Donor parameters: age, sex, creatinine, diabetes, cause of death, length of stay in ICU, calcification of donor renal artery (CRP expression level)
2. Perfusion pressure, perfusion time, perfusion temperature, perfusion vessel resistance index
3. Receptor factors: age, gender, height, weight, BMI, cause of kidney disease (hypertension, diabetes glomerulonephritis, polycystic kidney disease), dialysis time (month), dialysis type (blood/peritoneum), HLA mismatch number, smoking, diabetes, hypertension, heart disease, hyperlipidemia, anemia, complication index (CCI), ASA score (\>3 or ≤ 3), operation time, number of donor renal artery branches, number of donor renal vein branches, donor creatinine, cold ischemia time (mins), and the perfusion of the transplanted kidney ( judged by the fluorescence intensity after indocyanine green injection). Laboratory results: PRA (panel-reactive antibody), blood creatinine, estimated glomerular filtration rate (eGFR), blood lactate level, postoperative urine volume. Graft loss, culture result of irrigation solution (bacteria). Sample acquisition: obtaining the blood and urine samples of the recipient and measuring the expression level of globulin A in the serum. In the process of kidney transplantation, the donor's renal artery vessel wall and the recipient's external iliac artery vessel wall were obtained. The blood vessel wall was stained with calcification, CRP to evaluate the calcification of the donor and recipient vessels.

Eligibility criteria: Inclusion Criteria:

* Age 18-60 years old, gender unlimited
* Volunteer to participate in this clinical trial and sign the informed consent form
* Suffering from end-stage renal disease
* Planned kidney transplantation
* The expanded standard donors (ECD) were obtained

  * The expanded standard kidney donor is defined as: aged cadaver donors over 60 years old or two or three of the following conditions between 50 and 60 years old: death due to cerebrovascular disease; Hypertension; The blood creatinine level before donation was greater than 133umol/L.

Exclusion Criteria:

* Active infection
* Living donor kidney recipient
* Acute rejection
* Second kidney transplantation
* Combined transplantation (combined liver and kidney, combined pancreas and kidney)
* Patients who take other clinical trial drugs or participate in other clinical studies
* Unable to continue the research
* Patients who are judged by the researcher to be unsuitable for this clinical trial

Primary outcomes:
measure: Rate of delayed renal function (DGF)
timeFrame: 1 week after surgery
Secondary outcomes:
measure: Estimated glomerular filtration rate
timeFrame: 3, 6, 12 months after surgery
measure: Rate of primary non-function (PNF)
timeFrame: 1 months after surgery
measure: Graft survival and recipient survival
timeFrame: 1 year follow-up
measure: Complications
timeFrame: within 90 days after operation
measure: Patient death
timeFrame: 1 year follow-up
Other outcomes:
measure: Hospitalization expenses
timeFrame: 3, 6, 12 months after surgery
Locations:
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
Study officials:
affiliation: China-Japan Friendship Hospital
name: Zhou Xiaofeng, MD
role: STUDY_CHAIR
References:
citation: Hamar M, Urbanellis P, Kaths MJ, Kollmann D, Linares I, Ganesh S, Wiebe A, Cen JY, Yip P, John R, Konvalinka A, Mucsi I, Ghanekar A, Bagli D, Grant D, Robinson LA, Selzner M. Normothermic Ex Vivo Kidney Perfusion Reduces Warm Ischemic Injury of Porcine Kidney Grafts Retrieved After Circulatory Death. Transplantation. 2018 Aug;102(8):1262-1270. doi: 10.1097/TP.0000000000002245.
citation: Nicholson ML, Hosgood SA. Renal transplantation after ex vivo normothermic perfusion: the first clinical study. Am J Transplant. 2013 May;13(5):1246-52. doi: 10.1111/ajt.12179. Epub 2013 Feb 22.
citation: Mazilescu LI, Urbanellis P, Kim SJ, Goto T, Noguchi Y, Konvalinka A, Reichman TW, Sayed BA, Mucsi I, Lee JY, Robinson LA, Ghanekar A, Selzner M. Normothermic Ex Vivo Kidney Perfusion for Human Kidney Transplantation: First North American Results. Transplantation. 2022 Sep 1;106(9):1852-1859. doi: 10.1097/TP.0000000000004098. Epub 2022 Mar 1.