Somatostatin in Living Donor Liver Transplantation

NCT ID: NCT04107428

Last Updated: 2019-09-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-31
• Study Completion Date: 2022-02-28

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.

Conditions

End Stage Liver DIsease; Portal Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Somatostatin

Group Type: ACTIVE_COMPARATOR

Somatostatin

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy

UNKNOWN

Sponsor Role: collaborator

CEINGE - Biotecnologie Avanzate, Napoli, Italia

UNKNOWN

Sponsor Role: collaborator

King Faisal Specialist Hospital & Research Center

OTHER

Sponsor Role: lead

Responsible Party

Roberto Troisi

Principal Investigator, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Roberto Troisi, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

King Faisal Specialist Hospital & Research Center

Dieter Broering, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

King Faisal Specialist Hospital & Research Center

Central Contacts

Roberto Troisi, MD, PhD

Role: CONTACT

roberto.troisi@unina.it

+966(0)11-4482123 ext. 43648

Kris Hervera Marquez

Role: CONTACT

krhervera@kfshrc.edu.sa

.: (+966-11) 4647272 ext. 76163

Other Identifiers

C380/981/40

Identifier Type: -

Identifier Source: org_study_id