Ascorbic Acid to Prevent Postreperfusion Syndrome in Liver Transplantation

Liver Transplantation Clinical Trial

— VITACTOH  

Official title:

Intravenous Vitamin C for the Prevention of Postreperfusion Syndrome in Orthotopic Liver Transplantation From Deceased Donors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05754242
• Other study ID #: EC 20/606
• Status: Recruiting
• Phase: Phase 2
• Start date: November 17, 2020
• Est. completion date: July 30, 2023

Study information

• Verified date: March 2023
• Source: Hospital Universitario Ramon y Cajal
• Contact: Luis Gajate, MD PhD
• Phone: +34913368269
• Email: gajate.luis[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test the efficacy of intravenous ascorbic acid in preventing the postreperfusion syndrome in liver transplantation. The main questions it aims to answer are:

• Can intravenous ascorbic acid prevent postreperfusion syndrome in liver transplantation ?

• Can ascorbic acid decrease the incidence of liver graft dysfunction after liver transplantation?

• Can ascorbic acid decreased the incidence of postoperative complications after liver transplantation ?

Participants will receive 1.5 g of intravenous ascorbic acid diluted in 100 ml of saline or 100 ml of saline alone, during the anhepatic phase of liver transplantation before reperfusion of the new graft.

Researchers will compared the incidence of postreperfusion syndrome in both groups.

Description:

Researches will compared:

• Incidence of postreperfusion syndrome in liver transplantation

• Changes in interleukin values and other inflammatory markers before and after transplantation

• Incidence of liver graft dysfunction between groups

• Incidence of acute renal failure and other complications between groups

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: July 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 67 Years

Eligibility

Inclusion Criteria:

• Patients undergoing liver transplantation

Exclusion Criteria:

• Pregnancy

• Allergy to ascorbic acid

• Nephrolithiasis

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

• Hyperoxaluria

• Hyperuricemia

• Haemochromatosis

• Sickle cell anemia

• Serum Creatinine > 1.2 mg/dl in women and 1.3 mg/dl in men

• Split liver graft

• Acute liver failure

• Living donor liver transplantation

• Controlled donor asystolia

• Treatment with: indinavir, Vitamin B12, Cyclosporine, iron, deferoxamine, disulfiram

Related Conditions & MeSH terms

• Ascorbic Acid
• Liver Transplantation
• Postreperfusion Syndrome
• Syndrome

Intervention

Drug:
• Ascorbic acid
1.5 gr of ascorbic acid
• 0.9% Saline solution
100 ml of 0.9% saline solution

Locations

Country	Name	City	State
Spain	Hospital Universitario RAmon y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

References & Publications (12)

Aggarwal S, Kang Y, Freeman JA, Fortunato FL, Pinsky MR. Postreperfusion syndrome: cardiovascular collapse following hepatic reperfusion during liver transplantation. Transplant Proc. 1987 Aug;19(4 Suppl 3):54-5. No abstract available. — View Citation

Bezinover D, Kadry Z, McCullough P, McQuillan PM, Uemura T, Welker K, Mastro AM, Janicki PK. Release of cytokines and hemodynamic instability during the reperfusion of a liver graft. Liver Transpl. 2011 Mar;17(3):324-30. doi: 10.1002/lt.22227. — View Citation

Blanot S, Gillon MC, Ecoffey C, Lopez I. Circulating endotoxins during orthotopic liver transplantation and post-reperfusion syndrome. Lancet. 1993 Oct 2;342(8875):859-60. doi: 10.1016/0140-6736(93)92715-6. No abstract available. — View Citation

Blanot S, Gillon MC, Lopez I, Ecoffey C. Circulating endotoxins and postreperfusion syndrome during orthotopic liver transplantation. Transplantation. 1995 Jul 15;60(1):103-6. doi: 10.1097/00007890-199507150-00019. No abstract available. — View Citation

Fowler AA 3rd, Syed AA, Knowlson S, Sculthorpe R, Farthing D, DeWilde C, Farthing CA, Larus TL, Martin E, Brophy DF, Gupta S; Medical Respiratory Intensive Care Unit Nursing; Fisher BJ, Natarajan R. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med. 2014 Jan 31;12:32. doi: 10.1186/1479-5876-12-32. — View Citation

Girn HR, Ahilathirunayagam S, Mavor AI, Homer-Vanniasinkam S. Reperfusion syndrome: cellular mechanisms of microvascular dysfunction and potential therapeutic strategies. Vasc Endovascular Surg. 2007 Aug-Sep;41(4):277-93. doi: 10.1177/1538574407304510. — View Citation

Ishine N, Yagi T, Ishikawa T, Sasaki H, Nakagawa K, Tanaka N. Hemodynamic analysis of post-reperfusion syndrome and the effect of preventing this syndrome using thromboxane A2 synthetase inhibitor (OKY-046) in swine liver transplantation. Transplant Proc. 1997 Feb-Mar;29(1-2):378-81. doi: 10.1016/s0041-1345(96)00127-3. No abstract available. — View Citation

Paugam-Burtz C, Kavafyan J, Merckx P, Dahmani S, Sommacale D, Ramsay M, Belghiti J, Mantz J. Postreperfusion syndrome during liver transplantation for cirrhosis: outcome and predictors. Liver Transpl. 2009 May;15(5):522-9. doi: 10.1002/lt.21730. — View Citation

Siniscalchi A, Dante A, Spedicato S, Riganello L, Zanoni A, Cimatti M, Pierucci E, Bernardi E, Miklosova Z, Moretti C, Faenza S. Hyperdynamic circulation in acute liver failure: reperfusion syndrome and outcome following liver transplantation. Transplant Proc. 2010 May;42(4):1197-9. doi: 10.1016/j.transproceed.2010.03.097. — View Citation

Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg. 2000 Mar;135(3):326-31. doi: 10.1001/archsurg.135.3.326. — View Citation

Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors. 2009 Jan-Feb;35(1):5-13. doi: 10.1002/biof.7. — View Citation

Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. J Res Pharm Pract. 2016 Apr-Jun;5(2):94-100. doi: 10.4103/2279-042X.179569. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postreperfusion syndrome	When mean arterial pressure decreases by more than 30% relative to the value at the end of the anhepatic phase and lasts for at least 1 min	Within the first 5 minutes after reperfusion of the grafted liver
Secondary	Ascorbic acid serum levels	Quantification of ascorbic acid levels before and after liver transplantation	Immediately before induction of anesthesia and 12 hours after repercussion of the graft
Secondary	Interleukin1beta (IL-1ß) levels	Quantification of IL-1ß before and after liver transplantation	Immediately before induction of anesthesia and 12 hours after repercussion of the graft
Secondary	Tumor Necrosis Factor-alpha (TNFa) levels	Quantification of TNFa before and after liver transplantation	Immediately before induction of anesthesia and 12 hours after repercussion of the graft
Secondary	Interleukin-6 levels (IL-6)	Quantification of IL-6 before and after liver transplantation	Immediately before induction of anesthesia and 12 hours after repercussion of the graft
Secondary	Interleukin-8 (IL-8) levels	Quantification of IL-8 before and after liver transplantation	Immediately before induction of anesthesia and 12 hours after repercussion of the graft
Secondary	Interferon gamma (IFN?) levels	Quantification of IFN? before and after liver transplantation	Immediately before induction of anesthesia and 12 hours after repercussion of the graft
Secondary	Primary graft dysfunction	Incidence of primary graft nonfunction and early graft dysfunction. Graft nonfunction: lack of liver function leading to death if not retransplanted Early graft dysfunction: Olthoff's criteria	First postoperative week
Secondary	Acute renal failure	Postoperative renal failure after liver transplantation as Kidney Disease Improving Global Outcomes (KDIGO) definition	First postoperative week
Secondary	Mechanical ventilation	Duration of mechanical ventilation (hours) until extubation of the patient	Postoperative until day 30
Secondary	Mortality	Mortality of any cause	Up to day 30
Secondary	Length of hospitalization	Length of stay in hospital (days)	Through study completion (30 days)
Secondary	Length of Intensive Care Unit (ICU) stay	Length of ICU stay	Through study completion (30 days)
Secondary	Duration of vasopressor support after transplantation	Duration of vasopressor or inotropic support after transplantation	Postoperative until study completion (30 days)
Secondary	Maximum dose of vasopressor support after transplantation	Maximum dose of vasopressor or inotropic support after transplantation	Postoperative until study completion (30 days)