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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05754242
Other study ID # EC 20/606
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
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
Health authority
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

Study Design


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 allClick 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)
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