Clinical trial NCT05754242: Ascorbic Acid to Prevent Postreperfusion Syndrome in Liver Transplantation
Official title: Intravenous Vitamin C for the Prevention of Postreperfusion Syndrome in Orthotopic Liver Transplantation From Deceased Donors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Liver Transplantation
Postreperfusion Syndrome
Ascorbic Acid
Keywords: Postreperfusion syndrome
Lead sponsor: Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2023-03-03
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Postreperfusion syndrome
timeFrame: Within the first 5 minutes after reperfusion of the grafted liver
Secondary outcomes:
measure: Ascorbic acid serum levels
timeFrame: Immediately before induction of anesthesia and 12 hours after repercussion of the graft
measure: Interleukin1beta (IL-1β) levels
timeFrame: Immediately before induction of anesthesia and 12 hours after repercussion of the graft
measure: Tumor Necrosis Factor-alpha (TNFα) levels
timeFrame: Immediately before induction of anesthesia and 12 hours after repercussion of the graft
measure: Interleukin-6 levels (IL-6)
timeFrame: Immediately before induction of anesthesia and 12 hours after repercussion of the graft
measure: Interleukin-8 (IL-8) levels
timeFrame: Immediately before induction of anesthesia and 12 hours after repercussion of the graft
measure: Interferon gamma (IFNγ) levels
timeFrame: Immediately before induction of anesthesia and 12 hours after repercussion of the graft
measure: Primary graft dysfunction
timeFrame: First postoperative week
measure: Acute renal failure
timeFrame: First postoperative week
measure: Mechanical ventilation
timeFrame: Postoperative until day 30
measure: Mortality
timeFrame: Up to day 30
measure: Length of hospitalization
timeFrame: Through study completion (30 days)
measure: Length of Intensive Care Unit (ICU) stay
timeFrame: Through study completion (30 days)
measure: Duration of vasopressor support after transplantation
timeFrame: Postoperative until study completion (30 days)
measure: Maximum dose of vasopressor support after transplantation
timeFrame: Postoperative until study completion (30 days)
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario RAmon y Cajal
Study officials:
affiliation: Hospital Universitario Ramón y Cajal
name: Luis Gajate, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.