Ascorbic Acid to Prevent Postreperfusion Syndrome in Liver Transplantation

NCT05754242 | Unknown Phase 2 DMC

• 1 other identifier: EC 20/606
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplantation; Postreperfusion Syndrome; Ascorbic Acid

Keywords

Postreperfusion syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Ascorbic acid serum levels

  Immediately before induction of anesthesia and 12 hours after repercussion of the graft

• Interleukin1beta (IL-1β) levels

  Immediately before induction of anesthesia and 12 hours after repercussion of the graft

• Tumor Necrosis Factor-alpha (TNFα) levels

  Immediately before induction of anesthesia and 12 hours after repercussion of the graft

• Interleukin-6 levels (IL-6)

  Immediately before induction of anesthesia and 12 hours after repercussion of the graft

• Interleukin-8 (IL-8) levels

  Immediately before induction of anesthesia and 12 hours after repercussion of the graft

Study Arms (2)

Ascorbic acid

EXPERIMENTAL

1.5 gr of ascorbic acid diluted in 100 ml of 0.9% saline solution will be administered intravenously during the anhepatic phase of liver transplantation

Drug: Ascorbic acid

Saline solution

PLACEBO COMPARATOR

100 ml of 0.9% saline solution will be administered during the anhepatic phase of liver transplantation

Drug: 0.9% Saline solution

Interventions

Ascorbic acid DRUG

1.5 gr of ascorbic acid

Also known as: Vitamin C

Ascorbic acid

0.9% Saline solution DRUG

100 ml of 0.9% saline solution

Also known as: Saline

Saline solution

Eligibility Criteria

• Age: 18 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing liver transplantation

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Universitario Ramon y Cajal: lead

Study Sites (1)

Hospital Universitario RAmon y Cajal

Madrid, 28034, Spain

RECRUITING

Related Publications (13)

• 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.

  PMID: 3303534 BACKGROUND

• 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.

  PMID: 20534260 BACKGROUND

• 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.

  PMID: 19399736 BACKGROUND

• 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.

  PMID: 7624932 BACKGROUND

• 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.

  PMID: 21384515 BACKGROUND

• 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.

  PMID: 8104281 BACKGROUND

• 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.

  PMID: 9123045 BACKGROUND

• 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.

  PMID: 17704330 BACKGROUND

• 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.

  PMID: 19319840 BACKGROUND

• 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.

  PMID: 10722036 BACKGROUND

• 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.

  PMID: 27162802 BACKGROUND

• 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.

  PMID: 24484547 BACKGROUND

• Gajate L, de la Hoz I, Espino M, Martin Gonzalez MDC, Fernandez Martin C, Martin-Grande A, Parise Roux D, Pastor O, Villahoz J, Rodriguez-Gandia MA, Nuno Vazquez J. Intravenous Ascorbic Acid for the Prevention of Postreperfusion Syndrome in Orthotopic Liver Transplantation: Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2023 Dec 15;12:e50091. doi: 10.2196/50091.

  PMID: 38100226 DERIVED

MeSH Terms

Interventions

Ascorbic Acid; Saline Solution; Sodium Chloride

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Luis Gajate, MD PhD

  Hospital Universitario Ramón y Cajal

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis Gajate, MD PhD

CONTACT

+34913368269; gajate.luis@gmail.com

Ines de la Hoz, MD

CONTACT

+34913368269; delahozpoloines@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 3, 2023
• Study Start: November 17, 2020
• Primary Completion: June 30, 2023
• Study Completion: July 30, 2023
• Last Updated: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 6 months after publication
• Access Criteria: Access by mail to principal investigator: gajate.luis@gmail.com

Locations

ES (1)