Somatostatin in Living Donor Liver Transplantation

Somatostatin as Inflow Modulator in Adult-to-adult Living Donor Liver Transplantation: a Randomized, Double-blind, Placebo-controlled Trial

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).

Study Overview

• Status: Unknown
• Conditions: Portal Hypertension; End Stage Liver DIsease
• Intervention / Treatment: Drug: Somatostatin; Drug: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Roberto Troisi, MD, PhD; Phone Number: 43648 +966(0)11-4482123; Email: roberto.troisi@unina.it
• Study Contact Backup: Name: Kris Hervera Marquez; Phone Number: 76163 .: (+966-11) 4647272; Email: krhervera@kfshrc.edu.sa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; A bolus of 5cc of saline will be administered intravenously after graft reperfusion (after portal and arterial anastomosis) over a 2 minutes period, followed by a continuous infusion of 2.5 cc of saline/hour for 10 days.
Active Comparator: Somatostatin	Drug: Somatostatin; A bolus of 5cc of saline containing 500 mcg of somatostatin will be administered intravenously after graft reperfusion (after portal and arterial anastomosis) over a 2 minutes period, followed by a continuous infusion of 250 mcg per hour of somatostatin (infusion rate 2.5 cc/hour) for 10 days.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: King Faisal Specialist Hospital & Research Center
• Collaborators: Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy; CEINGE - Biotecnologie Avanzate, Napoli, Italia
• Investigators: Principal Investigator: Roberto Troisi, MD, PhD, King Faisal Specialist Hospital & Research Centre; Principal Investigator: Dieter Broering, MD, PhD, King Faisal Specialist Hospital & Research Centre

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): August 1, 2020
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: adult-to-adult living donor liver transplantation; small-for-size syndrome; graft hyperperfusion
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Liver Diseases; End Stage Liver Disease; Hypertension, Portal; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Somatostatin
• Other Study ID Numbers: C380/981/40

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No