VITACTOH: Ascorbic Acid to Prevent Postreperfusion Syndrome in Liver Transplantation

• Sponsor: Hospital Universitario Ramon y Cajal (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05754242
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 32.4
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Transplantation; Postreperfusion Syndrome; Ascorbic Acid	Drug: Ascorbic acid; Drug: 0.9% Saline solution	Phase 2

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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Intravenous Vitamin C for the Prevention of Postreperfusion Syndrome in Orthotopic Liver Transplantation From Deceased Donors
• Actual Study Start Date: Nov 17, 2020
• Anticipated Primary Completion Date: Jun 30, 2023
• Anticipated Study Completion Date: Jul 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ascorbic acid 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; 1.5 gr of ascorbic acid; Other Names: Vitamin C
Placebo Comparator: Saline solution 100 ml of 0.9% saline solution will be administered during the anhepatic phase of liver transplantation	Drug: 0.9% Saline solution; 100 ml of 0.9% saline solution; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Postreperfusion syndrome [Within the first 5 minutes after reperfusion of the grafted liver]

   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

Secondary Outcome Measures

1. Ascorbic acid serum levels [Immediately before induction of anesthesia and 12 hours after repercussion of the graft]

   Quantification of ascorbic acid levels before and after liver transplantation

2. Interleukin1beta (IL-1β) levels [Immediately before induction of anesthesia and 12 hours after repercussion of the graft]

   Quantification of IL-1β before and after liver transplantation

3. Tumor Necrosis Factor-alpha (TNFα) levels [Immediately before induction of anesthesia and 12 hours after repercussion of the graft]

   Quantification of TNFα before and after liver transplantation

4. Interleukin-6 levels (IL-6) [Immediately before induction of anesthesia and 12 hours after repercussion of the graft]

   Quantification of IL-6 before and after liver transplantation

5. Interleukin-8 (IL-8) levels [Immediately before induction of anesthesia and 12 hours after repercussion of the graft]

   Quantification of IL-8 before and after liver transplantation

6. Interferon gamma (IFNγ) levels [Immediately before induction of anesthesia and 12 hours after repercussion of the graft]

   Quantification of IFNγ before and after liver transplantation

7. Primary graft dysfunction [First postoperative week]

   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

8. Acute renal failure [First postoperative week]

   Postoperative renal failure after liver transplantation as Kidney Disease Improving Global Outcomes (KDIGO) definition

9. Mechanical ventilation [Postoperative until day 30]

   Duration of mechanical ventilation (hours) until extubation of the patient

10. Mortality [Up to day 30]

    Mortality of any cause

11. Length of hospitalization [Through study completion (30 days)]

    Length of stay in hospital (days)

12. Length of Intensive Care Unit (ICU) stay [Through study completion (30 days)]

    Length of ICU stay

13. Duration of vasopressor support after transplantation [Postoperative until study completion (30 days)]

    Duration of vasopressor or inotropic support after transplantation

14. Maximum dose of vasopressor support after transplantation [Postoperative until study completion (30 days)]

    Maximum dose of vasopressor or inotropic support after transplantation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 67 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario RAmon y Cajal	Madrid		Spain	28034

Sponsors and Collaborators

• Hospital Universitario Ramon y Cajal

Investigators

• Principal Investigator: Luis Gajate, MD PhD, Hospital Universitario Ramón y Cajal

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Luis Gajate Martín, Principal investigator, Hospital Universitario Ramon y Cajal
• ClinicalTrials.gov Identifier: NCT05754242
• Other Study ID Numbers: EC 20/606
• First Posted: Mar 3, 2023
• Last Update Posted: Mar 3, 2023
• Last Verified: Mar 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Luis Gajate Martín, Principal investigator, Hospital Universitario Ramon y Cajal: Postreperfusion syndrome
• Additional relevant MeSH terms: Syndrome; Ascorbic Acid

Study Results

No Results Posted as of Mar 3, 2023