Somatostatin in Living Donor Liver Transplantation

Phase 4

• Conditions: End Stage Liver DIsease; Portal Hypertension
• Interventions: Drug: Somatostatin; Drug: Placebo

• Registration Number: NCT04107428
• Lead Sponsor: King Faisal Specialist Hospital & Research Center

Brief Summary

Aim of the study is to investigate the safety and the efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing Adult-to-Adult living donor liver transplantation (A2ALDLT).

Detailed Description

In liver transplantation (LT) portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. Perioperative somatostatin infusion has been shown to be safe, to reduce the Hepatic Vein to Portal Vein Gradients and to preserve the arterial inflow to the graft in whole liver transplantation. In partial grafts, the pharmacological action of somatostatin could reduce the graft damage due to portal hyperperfusion and arterial hypoperfusion, reducing the incidence of small-for-size syndrome and graft loss and improving the patients survival.

Objective of the study is to investigate the safety and the efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing Adult-to-Adult living donor liver transplantation (A2ALDLT).

Fifty-six patients undergoing A2ALDLT for ESLD and CSPH will be randomized double-blindly to receive somatostatin or placebo (1:1). The study drug will be administered intraoperatively as 5ml bolus (somatostatin: 500 μg), followed by a 2.5 ml/hour infusion (somatostatin: 250 μg/hour) for 10 days. Hepatic and systemic hemodynamic will be measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) will be analysed through histological and protein expression analysis.

The primary endpoint of the study will be the portal vein flow reduction measured at the end of liver transplant. Secondary end-points will be the reduction in the portal vein pressure, the rate of patients requiring surgical inflow modulation, the incidence of small for size syndrome, the severity of the ischemia reperfusion injury, the need for early re-transplantation (6 months), the incidence of adverse and serious adverse events, the 90-day mortality.

This randomized controlled trial could be the first to show the efficacy of somatostatin as modulator of the graft inflow in living-donor liver transplantation and potential improvement in graft and patient survival.

Study Timeline

• Status Verified: 2019-09
• Study First Submitted: 2019-09-24
• Study First Submitted QC: 2019-09-25
• Last Update Submitted: 2019-09-25
• Study First Posted: 2019-09-27
• Last Update Posted: 2019-09-27
• Study Start: 2019-12
• Primary Completion: 2020-08
• Study Completion: 2022-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Adult patients (> 18 years old) undergoing Adult-to-Adult Living donor Liver Transplantation (LDLT) (right or left lobe)
• Indication for LDLT: End Stage Liver Disease with Portal Hypertension (HVPG ≥ 10mmHg)

Exclusion Criteria

• Complete portal vein thrombosis (pre-operative or intraoperative diagnosis)
• Hepatopulmonary hypertension
• Adult-to-Adult Living donor liver transplantation for Fulminant hepatic failure
• Recipients of multiple solid organ transplants
• History of cardiac arrhythmias

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Somatostatin	Somatostatin	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Portal venous flow changes	Day 0 - At the end of liver transplantation surgery, before skin closure	Flow measured with transit time flow measurement system

Secondary Outcome Measures

Name	Time	Method
Rate of patients presenting a significant portal venous flow reduction (-20%)	Day 0 - At the end of liver transplantation surgery, before skin closure	Flow measured with transit time flow measurement system
Mortality	90 days
Rate of patients requiring surgical inflow modulation	Day 0 - At the end of liver transplantation surgery, before skin closure
Changes in hepatic artery flow	Day 0 - At the end of liver transplantation surgery, before skin closure	Flow measured with transit time flow measurement system
Rates of patients requiring early re-transplantation	6 months
Incidence of Small-for-size syndrome	30 days
Changes in postoperative portal venous flow	Postoperative day 1, 7 and 14	Flow measured by transabdominal ultrasound
Incidence of adverse and serious adverse events	18 months