Clinical trial NCT02613195: Clinical Trial of Hydrogen-Rich Celsior Solution Applied in Aging DBD Liver/Kidney Transplantation
Official title: Hydrogen-Rich Celsior Solution Improve the Quality of Aging DBD Grafts in Liver/Kidney Transplantation: Prospective, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Evidence of Liver Transplantation
Keywords: Ischemia-Reperfusion Injury
oxidative stress
organ preservation
Hydrogen
Kidney Transplantation
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2015-11-24
Enrollment: 20
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

Donors:

1. Age of the donor ≥60 yrs.
2. The donor has no historical records of drug abuse, alcoholic abuse, homosexual,or drug addiction, etc.
3. Evaluate infections and infectious disease of the donor.
4. History of malignant tumor;
5. History of hypertension, diabetes, hemophilia, or other anticoagulant disease,kidney donor should not have a history of kidney disease.
6. Daily urine volume is approximately normal.
7. 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.
8. 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).
9. The potential donor should has a systolic blood pressure ≥ 50 mm Hg (1mmHg=0.133 kPa) and arterial SaO \> 80%.
10. Liver Biochemistry: alanine aminotransferase (ALT) ≤ 6ULN, total bilirubin (TBil) ≤ 50umol/L;Kidney Biochemistry: serum creatinine (sCre) ≤ 2ULN;
11. Negative anti-HIV antibody;
12. Negative bacterial and fungal culture in blood;
13. Ultrasonic diagnosis of fatty liver, trauma, hematoma, lithiasis, etc., as well as size of both kidney, hydronephrosis, nephrolithiasis, etc. if possible.
14. 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：

1. Aged between 18-65 years old
2. MELD score ≤25,BMI≤25
3. Patients with tumor,the expected lifetime≥6 months
4. 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.

Primary outcomes:
measure: Change From Baseline in Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT)
timeFrame: up to 6 months
measure: Change From Baseline in direct bilirubin(DBil)/total bilirubin(TBil)
timeFrame: up to 6 months
measure: Change From Baseline in creatinine
timeFrame: up to 6 months
measure: Change From Baseline in glomerular filtration rate（GFR）
timeFrame: up to 6 months
Secondary outcomes:
measure: Pathological score of liver/kidney preservation injury during surgery
timeFrame: during surgery
measure: Mitochondrial function index of hepatocyte/nephrocyte during surgery
timeFrame: during surgery
measure: The total incidence of adverse events/incidence of severe adverse events
timeFrame: up to 6 months
measure: postoperative complications
timeFrame: up to 6 months
measure: Early graft function incidence
timeFrame: baseline and 6 months
measure: Graft dysfunction incidence
timeFrame: baseline and 6 months
measure: Recipient survival
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ren Ji Hospital
state: Shanghai
city: Shanghai
country: China
facility: Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Study officials:
affiliation: Deparment of Liver Surgery
name: Xia Qiang, investigator
role: STUDY_DIRECTOR
References:
citation: Abe T, Li XK, Yazawa K, Hatayama N, Xie L, Sato B, Kakuta Y, Tsutahara K, Okumi M, Tsuda H, Kaimori JY, Isaka Y, Natori M, Takahara S, Nonomura N. Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury. Transplantation. 2012 Jul 15;94(1):14-21. doi: 10.1097/TP.0b013e318255f8be.
citation: Qian L, Shen J. Hydrogen therapy may be an effective and specific novel treatment for acute graft-versus-host disease (GVHD). J Cell Mol Med. 2013 Aug;17(8):1059-63. doi: 10.1111/jcmm.12081. Epub 2013 Jun 7.
citation: Buchholz BM, Masutani K, Kawamura T, Peng X, Toyoda Y, Billiar TR, Bauer AJ, Nakao A. Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation. Transplantation. 2011 Nov 15;92(9):985-92. doi: 10.1097/TP.0b013e318230159d.
citation: Liu Y, Yang L, Tao K, Vizcaychipi MP, Lloyd DM, Sun X, Irwin MG, Ma D, Yu W. Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release. BMC Gastroenterol. 2014 Jan 12;14:12. doi: 10.1186/1471-230X-14-12.
citation: Noda K, Shigemura N, Tanaka Y, Bhama J, D'Cunha J, Kobayashi H, Luketich JD, Bermudez CA. Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats. Transplantation. 2014 Sep 15;98(5):499-506. doi: 10.1097/TP.0000000000000254.