Somatostatin in Living Donor Liver Transplantation

Portal Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04107428
• Other study ID #: C380/981/40
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 2019
• Est. completion date: February 2022

Study information

• Verified date: September 2019
• Source: King Faisal Specialist Hospital & Research Center
• Contact: Roberto Troisi, MD, PhD
• Phone: +966(0)11-4482123
• Email: roberto.troisi[@]unina.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 56
• Est. completion date: February 2022
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Liver DIsease
• Hypertension, Portal
• Liver Diseases
• Portal Hypertension

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
King Faisal Specialist Hospital & Research Center	CEINGE - Biotecnologie Avanzate, Napoli, Italia, Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Rate of patients requiring surgical inflow modulation		Day 0 - At the end of liver transplantation surgery, before skin closure
Secondary	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
Secondary	Incidence of Small-for-size syndrome		30 days
Secondary	Changes in postoperative portal venous flow	Flow measured by transabdominal ultrasound	Postoperative day 1, 7 and 14
Secondary	Rates of patients requiring early re-transplantation		6 months
Secondary	Incidence of adverse and serious adverse events		18 months
Secondary	Mortality		90 days