End Stage Liver DIsease, Portal Hypertension
Conditions
Keywords
adult-to-adult living donor liver transplantation, small-for-size syndrome, graft hyperperfusion
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.
Interventions
DRUGSomatostatin
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.
DRUGPlacebo
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.
Sponsors
Federico II University of Naples, Department of Clinical Medicine and Surgery, Naples, Italy
CEINGE - Biotecnologie Avanzate, Napoli, Italia
King Faisal Specialist Hospital & Research Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized double-blinded placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Incidence of Small-for-size syndrome | 30 days | — |
| 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 |
| Rates of patients requiring early re-transplantation | 6 months | — |
| Incidence of adverse and serious adverse events | 18 months | — |
| Mortality | 90 days | — |
| Changes in postoperative portal venous flow | Postoperative day 1, 7 and 14 | Flow measured by transabdominal ultrasound |
Contacts
Primary ContactRoberto Troisi, MD, PhD
Backup ContactKris Hervera Marquez
Outcome results
None listed