A Study of Retrograde rEperfusion in Dbd Donor LIver Transplantation

Liver Transplantation Clinical Trial

— REDLIT  

Official title:

A Randomized Clinical Study of Retrograde Caval or Antegrade Portal Reperfusion for Early Graft Dysfunction Prevention in Deceased Brain Dead Donor Liver Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02423941
• Other study ID #: 616.36-089.843-008.6-07-037
• Status: Recruiting
• Phase: N/A
• First received: April 19, 2015
• Last updated: December 31, 2016
• Start date: April 2015
• Est. completion date: May 2017

Study information

• Verified date: December 2016
• Source: Republican Scientific and Practical Center for Organ and Tissue Transplantation
• Contact: Aliaksei E Shcherba, PhD
• Phone: +375293330689
• Email: aleina[@]tut.by
• Is FDA regulated: No
• Health authority: Belarus: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

To evaluate whether retrograde caval reperfusion of liver graft could be superior over antegrade portal reperfusion in regard of incidence and severity of early allograft liver dysfunction.

All eligible enrolled liver transplant candidates will be randomized to receive either:

1. retrograde caval, followed by sequential portal-arterial, reperfusion or

2. antegrade, sequential portal-arterial reperfusion.

Description:

We hypothesize that retrograde caval reperfusion could be superior over antegrade portal reperfusion in regard of incidence and severity of early allograft liver dysfunction.

Chi-square method of sample size estimation with a=0,05, b=0,20 and P1-P2 = 0,25 required a 41 subject per group (Stephen B Hulley, Steven R Cummings, Warren S Browner, Deborah G Grady, Thomas B Newman.-4th ed. Lippincott Williams & Wilkins, 2013).

After signing the informed consent 90 patients will be randomized to study and active-control group (45 each).

Only patients undergoing classical technique (retrohepatic IVC resection) of liver transplantation without vena-venous bypass will be enrolled to the study.

In the study group after completion of both caval anastomoses (super and infra-hepatic) the infra-hepatic cava-clamp is released and removed allowing the filling and flushing the liver retrogradely through the hepatic veins. 300 ml of blood is drained via donor portal vein and the vein will be clamped.

Suprahepatic cava-clamp is released and removed allowing venous return to the right atrium.

Portal vein anastomosis will be constructed. Before the last 2-3 stitches another 100 ml will be drained retrogradely. Recipient portal vein clamp is removed and liver will be reperfused antegradely. After that arterial and biliary anastomoses will be constructed.

In the control group cava-clamps are not removed until completion the portal vein anastomosis.

Chi-square test and regression analysis will be used to test the difference in incidence of early allograft liver dysfunction in the study groups.

Mann-Whitney test will be used to compare the median of highest aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels 24 and 48 hours post-reperfusion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: May 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 69 Years

Eligibility

Donor Inclusion Criteria:

• deceased brain dead

• age 18-59

• length of ICU treatment up to 7 days

• highest AST and ALT up to 200 UI/L

• macroscopic steatosis up to 30%

• highest serum sodium up to 165 mmol/L

• highest bilirubin 25 µmol/L

• application of norepinephrine is allowed

• preservation solution - HTK (Custodiol)

Recipient inclusion Criteria:

• age 18-69

• primary liver transplant

• full-size transplant

Technique of liver transplant:

• with IVC resection;

• without veno-venous bypass;

• sequential portal-arterial reperfusion

• flushing of portal vascular bed with 500 ml of called to 2-4 °C saline at back-table before implantataion

Recipient exclusion Criteria:

• live donor liver transplant

• reduced and split grafts;

• multi organ failure (including fulminant and UNOS status 1);

• fulminant hepatic failure

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Delayed Graft Function
• Liver Transplantation
• Reperfusion

Intervention

Procedure:
• Retrogade reperfusion
Retrogade caval reperfusion of the donor liver during the transplant procedure with consequent arterial reperfusion.
• Antegrade reperfusion
Antegrade conventional portal reperfusion of the donor liver during the transplant procedure with consequent arterial reperfusion.

Locations

Country	Name	City	State
Belarus	RSPC for organ and tissue transplantation, Minsk 9th clinic	Minsk

Sponsors (1)

Lead Sponsor	Collaborator
Republican Scientific and Practical Center for Organ and Tissue Transplantation

Country where clinical trial is conducted

Belarus, 

References & Publications (3)

Designing Clinical Research/Stephen B Hulley, Steven R Cummings, Warren S Browner, Deborah G Grady, Thomas B Newman.-4th ed. Lippincott Williams & Wilkins, 2013.-367p.]

Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091. — View Citation

Salvalaggio P, Afonso RC, Felga G, Ferraz-Neto BH. A proposal to grade the severity of early allograft dysfunction after liver transplantation. Einstein (Sao Paulo). 2013 Jan-Mar;11(1):23-31. English, Portuguese. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of early graft dysfunction (EAD)	EAD will be assessed according to Olthoff KM, et al. Liver Transpl. 2010. Severe EAD will be assessed according to P.R. Salvalaggio, et al. Transplantation Proceedings, 2012.	1-7 postoperative days	No
Secondary	Median aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels		24 and 48 hours post reperfusion	No
Secondary	Incidence of biliary strictures (anastomotic and nonanastomotic)	All biliary strictures would be diagnosed by cholangiography, either ERCP or MRCP. Ulrtrasound will be used as a screening tool to assign a cholestatic patient to cholangiography.	90 days after liver transplant procedure	Yes
Secondary	Incidence of in-hospital mortality		90 days after liver transplant procedure	No