Clinical Trial of Hydrogen-Rich Celsior Solution Applied in Aging DBD Liver/Kidney Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether hydrogen-rich Celsior solution improve the quality of aging grafts in liver/kidney transplantation.

Detailed Description
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The organ shortage has been rising to impede the development of organ transplantation.To find a solution, transplantation center is working on the application of marginal grafted liver or renal, especially the aging grafts. The most common inducement of organ dysfunction during the perioperation is liver/renal ischemia-reperfusion (I/R) injury, caused by the generation of cytotoxic oxygen radicals. Hydrogen gas is a kind of reducing gas, which has been reported to display antioxidant properties and protective effects against organ dysfunction induced by various I/R injuries. Investigators will investigate whether hydrogen-rich Celsior solution improve the quality of aging grafts in liver/ kidney transplantation.

Official Title
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Hydrogen-Rich Celsior Solution Improve the Quality of Aging DBD Grafts in Liver/Kidney Transplantation: Prospective, Randomized Clinical Trial

Conditions
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Evidence of Liver Transplantation

Intervention / Treatment
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* Drug: Hydrogen-Rich Celsior Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Donors: Age of the donor ≥60 yrs. The donor has no historical records of drug abuse, alcoholic abuse, homosexual,or drug addiction, etc. Evaluate infections and infectious disease of the donor. History of malignant tumor; History of hypertension, diabetes, hemophilia, or other anticoagulant disease,kidney donor should not have a history of kidney disease. Daily urine volume is approximately normal. Donor should be subjected to physical examination by medical doctor of OPO stuff before donation; the OPO stuff should realize whether the potential donor has infected lesion or not, such as abscess, ulcer, lymphadenectasis， etc., and evaluate infectious risk of recipient post-operationally. OPO stuff should realize the dynamic change of body temperature, as well as various intensive care parameters of the potential donor, it shall be very important to be sure whether the potential donor has pulmonary/ systemic infections or not,especially for whom has longer ICU duration (> 7 Days). The potential donor should has a systolic blood pressure ≥ 50 mm Hg (1mmHg=0.133 kPa) and arterial SaO > 80%. Liver Biochemistry: alanine aminotransferase (ALT) ≤ 6ULN, total bilirubin (TBil) ≤ 50umol/L;Kidney Biochemistry: serum creatinine (sCre) ≤ 2ULN; Negative anti-HIV antibody; Negative bacterial and fungal culture in blood; Ultrasonic diagnosis of fatty liver, trauma, hematoma, lithiasis, etc., as well as size of both kidney, hydronephrosis, nephrolithiasis, etc. if possible. Graft liver should be soft, normal color and even, no tumor or other abnormity;steatosis ≤ 30% by liver biopsy.Graft kidneys should have complete renal capsule with no congestion or bleeding;proximal tubular necrosis ≤ 50%, without obvious structural damage.Organ (liver and kidney) cold ischemia time (CIT) is determined as the time duration from cold preservation of organs to transplant re-perfusion. CIT of aging DBD liver and kidney graft should be ≤ 10 and16 hours, respectively. Recipients： Aged between 18-65 years old MELD score ≤25,BMI≤25 Patients with tumor,the expected lifetime≥6 months Agree to anticipate the trial and sign the informed consent Exclusion Criteria: Donor's age < 60 yrs; The donor has historical records of drug abuse, alcoholic abuse, homosexual, or drug addiction, etc. The donor is HIV infected, or has severe infection, or positive bacterial and/ or fungal culture results; Uncontrollable hypertension, diabetics; Malignant tumor; Unstable hemodynamic response or SaO status, such as systolic pressure <50 mm Hg (1mmHg=0.133 kPa) , or arterial SaO<80%. Liver Biochemistry: alanine aminotransferase (ALT)>6ULN, total bilirubin (TBil)>50umol/L; Graft liver has a steatosis >30%, or graft kidney has a proximal tubular necrosis>50% or obvious glomerular sclerosis.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrogen-rich Celsior solution<br>Using aging liver grafts（≥60 years old)，lavaged and cold stored with hydrogen-rich Celsior solution for 2-4 hours. | Drug: Hydrogen-Rich Celsior Solution<br>* Before the procedure, add hydrogen gas into Celsior solution. After harvesting the liver/kidney grafts, lavage and cold store the grafts with Hydrogen-Rich Celsior Solution.<br>* Other names: HR solution;|
| No Intervention: Celsior solution<br>Using aging liver/kidney grafts（≥60 years old）, lavaged and cold stored with common Celsior solution for 2-4 hours. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT) |  | up to 6 months | 
| Change From Baseline in direct bilirubin(DBil)/total bilirubin(TBil) |  | up to 6 months | 
| Change From Baseline in creatinine |  | up to 6 months | 
| Change From Baseline in glomerular filtration rate（GFR） |  | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological score of liver/kidney preservation injury during surgery |  | during surgery | 
| Mitochondrial function index of hepatocyte/nephrocyte during surgery |  | during surgery | 
| The total incidence of adverse events/incidence of severe adverse events |  | up to 6 months | 
| postoperative complications |  | up to 6 months | 
| Early graft function incidence |  | baseline and 6 months | 
| Graft dysfunction incidence |  | baseline and 6 months | 
| Recipient survival |  | baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemia-Reperfusion Injury, oxidative stress, organ preservation, Hydrogen, Kidney Transplantation