Clinical trial NCT02423941: A Study of Retrograde rEperfusion in Dbd Donor LIver Transplantation
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Transplantation
Reperfusion
Delayed Graft Function
Keywords: Liver Transplantation
Retrograde Reperfusion
Graft dysfunction
Randomized study
Lead sponsor: Republican Scientific and Practical Center for Organ and Tissue Transplantation
Sponsor class: OTHER
First posted: 2015-04-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of early graft dysfunction (EAD)
timeFrame: 1-7 postoperative days
Secondary outcomes:
measure: Median aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels
timeFrame: 24 and 48 hours post reperfusion
measure: Incidence of biliary strictures (anastomotic and nonanastomotic)
timeFrame: 90 days after liver transplant procedure
measure: Incidence of in-hospital mortality
timeFrame: 90 days after liver transplant procedure
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: RSPC for organ and tissue transplantation, Minsk 9th clinic
Study officials:
affiliation: RSPC for organ and tissue transplantation, Minsk 9th clinic
name: Oleg O Rummo, MD PhD
role: STUDY_CHAIR
References:
citation: 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.
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. doi: 10.1590/s1679-45082013000100006.
citation: 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.]