Trial Outcomes & Findings for Evaluation of Preimplantation Portal Vein and Hepatic Artery Flushing With Tacrolimus (NCT NCT01887171)

Results Overview

Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. Early allograft dysfunction will be assessed on the basis of highest levels of AST and ALT during 1-7 postoperative days.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

86 participants

Primary outcome timeframe

1-7 postoperative days after liver transplant procedure

Results posted on

2017-02-23

Participant Flow

Participant milestones

Participant milestones
Measure	Tacrolimus + HTK During back-table operation 1000 ml of HTK solution cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O. Tacrolimus: 1000 ml of HTK solution (Custodiol, Dr. Franz Köhler Chemie GmBH) cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O.	HTK Solution Only During back-table operation 1000 ml of HTK solution cooled to 2-4˚C would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin under gravity pressure of 40 cm H2O.
Overall Study STARTED	43	43
Overall Study COMPLETED	43	43
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Preimplantation Portal Vein and Hepatic Artery Flushing With Tacrolimus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tacrolimus + HTK n=43 Participants During back-table operation 1000 ml of HTK solution cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O. Tacrolimus: 1000 ml of HTK solution (Custodiol, Dr. Franz Köhler Chemie GmBH) cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O.	HTK Only n=43 Participants During back-table operation 1000 ml of HTK solution cooled to 2-4˚C would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin under gravity pressure of 40 cm H2O.	Total n=86 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	42 Participants n=5 Participants	42 Participants n=7 Participants	84 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	50 years n=5 Participants	50 years n=7 Participants	50 years n=5 Participants
Gender Female	18 Participants n=5 Participants	21 Participants n=7 Participants	39 Participants n=5 Participants
Gender Male	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants
Region of Enrollment Belarus	43 participants n=5 Participants	43 participants n=7 Participants	86 participants n=5 Participants

PRIMARY outcome

Timeframe: 1-7 postoperative days after liver transplant procedure

Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. Early allograft dysfunction will be assessed on the basis of highest levels of AST and ALT during 1-7 postoperative days.

Outcome measures

Outcome measures
Measure	Tacrolimus + HTK n=43 Participants During back-table operation 1000 ml of HTK solution cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O. Tacrolimus: 1000 ml of HTK solution (Custodiol, Dr. Franz Köhler Chemie GmBH) cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O.	HTK Solution Only n=43 Participants During back-table operation 1000 ml of HTK solution cooled to 2-4˚C would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin under gravity pressure of 40 cm H2O.
Early Allograft Dysfunction	6 Participants	18 Participants

SECONDARY outcome

Timeframe: liver biopsy taken at 2 hours after portal reperfusion

Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. A wedge resection of small (5x5mm) part of liver segment-III will be sampled at 2 hours after venous reperfusion. Rate of necrosis, inflammation, vascular thrombosis, cluster of differentiation (CD) 68 and High mobility group box 1 protein (HMGB1) staining will be assessed thereafter.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 0 and 20 min after portal reperfusion, 1 and 3 postoperative day

Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. After unclamping portal vein but before unclamping the inferior vena cava and after venting of first 100 ml of blood a 5 ml sample of blood (code is "HV") from a tube inserted into caval suture line will be taken. Another 5 ml sample of blood (code is "C") will be taken by puncture of one of hepatic veins 20 min later. Samples (5 ml each) of peripheral blood will be taken on 1st and 3d postoperative day (POD). P-selectin, interleukin-6, interleukin-8, tumor necrosis factor alfa (TNF-a) and macrophage inflammatory protein 1 alpha (MIP-1a) will be determined in samples "HV" and "C". Interleukin-8, elastase, TNF-a and vascular endothelial growth factor (VEGF) will be determined in samples of 1st and 3d POD.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 15 min and 2 hours after portal reperfusion

Protocol is restricted to liver transplants performed with classic technique with sequential portal-arterial reperfusion. Peripheral blood samples will be taken 15 min and 2 hours after portal reperfusion. Hyperfibrinolysis will be diagnosed by Thromboelastometry (ROTEM) if one or more following criteria are met: LI30\<85% or ML\>15% or LI60\<85% or A10 in Extem is by 15% is less then A10 in Aptem.

Outcome measures

Outcome data not reported

Adverse Events

Tacrolimus + HTK

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

HTK Solution

Serious events: 20 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tacrolimus + HTK n=12 participants at risk During back-table operation 1000 ml of HTK solution cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O. Tacrolimus: 1000 ml of HTK solution (Custodiol, Dr. Franz Köhler Chemie GmBH) cooled to 2-4˚C containing 20 ng/ml Tacrolimus would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin containing 20 ng/ml Tacrolimus under gravity pressure of 40 cm H2O.	HTK Solution n=22 participants at risk During back-table operation 1000 ml of HTK solution cooled to 2-4˚C would be given through intraportal (under gravity pressure of 40 cm H2O) and intraarterial infusion (under pressure of 40-50 mm Hg) followed by intraportal infusion of 200 ml 5% solution of Albumin under gravity pressure of 40 cm H2O.
Hepatobiliary disorders Early allograft dysfunction	50.0% 6/12 • Number of events 6	81.8% 18/22 • Number of events 18
Surgical and medical procedures Death	16.7% 2/12 • Number of events 2	13.6% 3/22 • Number of events 3

Other adverse events

Adverse event data not reported

Additional Information

Aliaksej Shcherba

Republican scientific and practical center for organ and tissue transplantation

Phone: +375293330689

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place