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

Evidence of Liver Transplantation Clinical Trial

— HRCSDBD  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02613195
• Other study ID #: RenJiH-20151020
• Status: Not yet recruiting
• Phase: Phase 3
• First received: October 24, 2015
• Last updated: November 20, 2015
• Start date: January 2016
• Est. completion date: February 2017

Study information

• Verified date: October 2015
• Source: RenJi Hospital
• Contact: Xia Qiang, investigator
• Phone: +86-21-68383775
• Email: xiaqiang[@]shsmu.edu.cn
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Evidence of Liver Transplantation

Intervention

Drug:
• Hydrogen-Rich Celsior Solution
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.

Locations

Country	Name	City	State
China	Deparment of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai
China	Ren Ji Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
RenJi Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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. Transplant — View 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):9 — View 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. — View 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.00000 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Aspartate Aminotransferase(AST)/Alanine Aminotransferase(ALT)		up to 6 months	Yes
Primary	Change From Baseline in direct bilirubin(DBil)/total bilirubin(TBil)		up to 6 months	Yes
Primary	Change From Baseline in creatinine		up to 6 months	Yes
Primary	Change From Baseline in glomerular filtration rate(GFR)		up to 6 months	Yes
Secondary	Pathological score of liver/kidney preservation injury during surgery		during surgery	Yes
Secondary	Mitochondrial function index of hepatocyte/nephrocyte during surgery		during surgery	Yes
Secondary	The total incidence of adverse events/incidence of severe adverse events		up to 6 months	Yes
Secondary	postoperative complications		up to 6 months	Yes
Secondary	Early graft function incidence		baseline and 6 months	Yes
Secondary	Graft dysfunction incidence		baseline and 6 months	Yes
Secondary	Recipient survival		baseline and 6 months	Yes