Clinical trial NCT04107428: Somatostatin in Living Donor Liver Transplantation
Official title: Somatostatin as Inflow Modulator in Adult-to-adult Living Donor Liver Transplantation: a Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: End Stage Liver DIsease
Portal Hypertension
Keywords: adult-to-adult living donor liver transplantation
small-for-size syndrome
graft hyperperfusion
Lead sponsor: King Faisal Specialist Hospital & Research Center
Sponsor class: OTHER
Collaborators: name: Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy
name: CEINGE - Biotecnologie Avanzate, Napoli, Italia
First posted: 2019-09-27
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double-blinded placebo-controlled trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Portal venous flow changes
timeFrame: Day 0 - At the end of liver transplantation surgery, before skin closure
Secondary outcomes:
measure: Rate of patients presenting a significant portal venous flow reduction (-20%)
timeFrame: Day 0 - At the end of liver transplantation surgery, before skin closure
measure: Rate of patients requiring surgical inflow modulation
timeFrame: Day 0 - At the end of liver transplantation surgery, before skin closure
measure: Changes in hepatic artery flow
timeFrame: Day 0 - At the end of liver transplantation surgery, before skin closure
measure: Incidence of Small-for-size syndrome
timeFrame: 30 days
measure: Changes in postoperative portal venous flow
timeFrame: Postoperative day 1, 7 and 14
measure: Rates of patients requiring early re-transplantation
timeFrame: 6 months
measure: Incidence of adverse and serious adverse events
timeFrame: 18 months
measure: Mortality
timeFrame: 90 days
Other outcomes:
Locations:
Study officials:
affiliation: King Faisal Specialist Hospital & Research Center
name: Roberto Troisi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: King Faisal Specialist Hospital & Research Center
name: Dieter Broering, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: