Normothermic Machine Perfusion (NMP) Versus Hypothermic Machine Perfusion (HMP) in Human Kidney Transplantation

Kidney Transplantation Clinical Trial

Official title:

Prospective Randomized Controlled Study Normothermic Pulse Perfusion Comparing and Hypothermic Machine Perfusion in Margin Deceased Donor Kidney Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05743751
• Other study ID #: 2022-NHLHCRF-LX-03
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 3, 2023
• Est. completion date: September 3, 2025

Study information

• Verified date: February 2023
• Source: China-Japan Friendship Hospital
• Contact: Zhou Xiaofeng, MD
• Phone: 17310336871
• Email: 13911250201[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: September 3, 2025
• Est. primary completion date: December 3, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypothermia
• Kidney Transplantation

Intervention

Device:
• Normothermic machine perfusion
XVIVO (perfusion company, Gothenburg, Sweden), functions to be included in perfusion equipment, cardiopulmonary bypass machine and neonatal cardiopulmonary bypass machine, including polyethylene pipeline, heating equipment (perfusion temperature 37 ?), venous pool (venous pressure is 0 mmHg, adjust the height of perfusion pool), centrifugal pump (arterial pressure is set at initial 75 mmHg, maintain 65 mmHg). The perfusion solution contains 215ml of dextran/albumin solution and 400ml of hematocrit, 2ml of 10% calcium gluconate, 1300u/L heparin and 400mg of cefazolin sodium. The oxygen/carbon dioxide ratio is (95%/5%, 2L/min) for continuous perfusion, and pO2 is maintained at 650mmHg during perfusion. During perfusion, continue to use verapamil, amino acid, glucose and insulin. Lactic acid Ringer solution (10ml/h) was used to supplement the lost circulation volume due to urine production during perfusion.
• Hypothermic machine perfusion
LifePort Kidney Transporter is designed to integrate with the clinical environment by using readily available supplies, requiring minimal user intervention, and by being easy to use. LifePort Kidney Transporter is a portable, isolated kidney perfusion and transport system, designed to support a donated kidney and to maintain the organ in a near-normal physiologic state under hypothermic aseptic conditions. An insulated plastic housing encloses the kidney and perfusate within a LifePort Kidney Transporter Disposable Perfusion Circuit. LifePort Kidney Transporter components include an Ice Container, Pump Deck, Control Panel, Outer Display, Bubble Detectors, External Connections Panel, sensors, and four lithium-ion batteries. Two handles make the unit easy to lift and carry

Locations

Country	Name	City	State
China	China-Japan Friendship Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Zhang Tianyu

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospitalization expenses	Total expenses of kidney transplantation	3, 6, 12 months after surgery
Primary	Rate of delayed renal function (DGF)	At least one dialysis is required within one week after kidney transplantation	1 week after surgery
Secondary	Estimated glomerular filtration rate	Calculated from serum creatinine levels to assess kidney function.	3, 6, 12 months after surgery
Secondary	Rate of primary non-function (PNF)	Dialysis is required because the transplanted kidney is nonfunctional	1 months after surgery
Secondary	Graft survival and recipient survival	Incidence of the Graft survival and recipient survival	1 year follow-up
Secondary	Complications	incidence of complications	within 90 days after operation
Secondary	Patient death	Death date after surgery and the reasons	1 year follow-up