Effects of Terlipressin and Somatostatin on Portal Pressure in Patients Undergoing Living Donor Liver Transplantation

NCT ID: NCT07304466

Last Updated: 2025-12-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-29
• Study Completion Date: 2027-03-30

Brief Summary

The goal of this clinical trial is to compare the effects of somatostatin and terlipressin on lowering portal pressure in patients with portal hypertension undergoing liver transplantation, and to investigate whether there are differences in clinical outcomes between the two drugs. The study will evaluate the decrease in portal pressure from baseline following drug administration at defined time points. It will also compare the effects of these drugs on hemodynamics, bleeding, and transfusion requirements. After baseline intraoperative direct portal pressure measurement, a bolus dose of the study drug will be administered, followed by continuous intravenous infusion intraoperatively and for 24 hours postoperatively. Direct portal pressure will be measured again 5 minutes after the bolus dose, after the portal vein anastomosis, after the hepatic artery anastomosis, and, if performed after splenic artery ligation. Hemodynamic parameters will be recorded, and the drugs will be compared in terms of their intraoperative hemodynamic effects. As elevated portal pressure is associated with increased bleeding, intraoperative blood loss and transfusion needs will also be assessed between the groups. Patients will be followed for 7 days postoperatively for clinical and laboratory outcomes.

Detailed Description

It is well known that elevated portal pressure during liver resection is associated with increased bleeding, greater surgical difficulty, impaired splanchnic perfusion, a higher incidence of postoperative kidney injury, and increased need for blood transfusion. Somatostatin, a peptide hormone used to reduce portal pressure, lowers portal venous pressure by altering splanchnic blood flow. It is frequently administered in patients with end-stage liver disease for indications such as controlling variceal bleeding and reducing intraoperative portal pressure. Terlipressin, a vasopressin analog, induces vasoconstriction, thereby decreasing portal inflow and venous congestion in the splanchnic circulation. By lowering portal pressure and exerting favorable systemic effects, it is often used intraoperatively in patients with impaired renal function. It has been associated with reduced surgical bleeding and improved renal perfusion.

Following baseline portal pressure measurement from the portal vein (PVP0), patients will receive treatment according to their study group. In the somatostatin (SS) group, a bolus dose of 250 mcg will be administered over 2 minutes, followed by a maintenance infusion at 2.5 mcg/kg/hour. In the terlipressin (TRP) group, a bolus dose of 1 mg will be given over 2 minutes, followed by a maintenance infusion at 2 mcg/kg/hour. Five minutes after completion of the bolus dose, portal pressure will be measured again and recorded with the corresponding time point (PVP1).

Once the hepatic and portal vein anastomoses are completed and graft reperfusion is achieved, the third portal pressure measurement will be taken (PVP2), and right after completion of the arterial anastomosis, the fourth portal pressure measurement will be performed (PVP3). If PVP exceeds 20 mmHg or Hepatic Venous Pressure Gradient (HVPG) exceeds 15 mmHg, splenic artery ligation will be performed to modify portal inflow and prevent small-for-size syndrome. If performed, this intervention will be recorded, and subsequent measurements will be repeated (PVP4)

Intraoperative ultrasound routinely performed by radiology will be used to measure arterial (peak systolic velocity, resistive index, acceleration time) and portal (flow volume) flow parameters, which will be documented. Hemodynamic data will be recorded throughout all measurements. The study drugs will be administered as continuous infusion for at least 24 hours, and if portal pressure remains elevated, the infusion may be extended up to a maximum of 5 days.

Conditions

Liver Transplantation; Portal Hypertension

Keywords

liver transplantation; portal pressure; portal hypertension; living donor liver transplantation; somatostatin; terlipressin

Study Design

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

Study Groups

Group Somatostatin (SS)

Somatostatin will be given.

Group Type: ACTIVE_COMPARATOR

Somatostatin

Intervention Type: DRUG

Following baseline portal pressure measurement from the portal vein (25 Gauge intracath, Bıçakçılar®) (PVP0), somatostatin (Somatex®) will be administered as a 250 mcg bolus over 2 minutes, followed by a continuous infusion at 2.5 mcg/kg/hour. Direct portal measurements will be done at the time points explained in the study description.

Intraoperative ultrasound (GE Healthcare®, linear probe) will be used to record arterial and portal flow parameters. Hemodynamic data will be collected during all measurements. The study drug will be infused continuously for at least 24 hours.

Group Terlipressin (TR)

Terlipressin will be given.

Group Type: ACTIVE_COMPARATOR

Terlipressin

Intervention Type: DRUG

Following baseline portal pressure measurement from the portal vein (25 Gauge intracath, Bıçakçılar®) (PVP0), terlipressin (Glypressin®) will be administered as a 1 mg bolus over 2 minutes, followed by a continuous infusion at 2 mcg/kg/hour.

Direct portal measurements will be done at the time points explained in the study description.

Intraoperative ultrasound (GE Healthcare®, linear probe) will be used to record arterial and portal flow parameters. Hemodynamic data will be collected during all measurements. The study drug will be infused continuously for at least 24 hours, and up to 5 days if portal pressure remains elevated.

Interventions

Somatostatin

Following baseline portal pressure measurement from the portal vein (25 Gauge intracath, Bıçakçılar®) (PVP0), somatostatin (Somatex®) will be administered as a 250 mcg bolus over 2 minutes, followed by a continuous infusion at 2.5 mcg/kg/hour. Direct portal measurements will be done at the time points explained in the study description.

Intraoperative ultrasound (GE Healthcare®, linear probe) will be used to record arterial and portal flow parameters. Hemodynamic data will be collected during all measurements. The study drug will be infused continuously for at least 24 hours.

Intervention Type: DRUG

Terlipressin

Following baseline portal pressure measurement from the portal vein (25 Gauge intracath, Bıçakçılar®) (PVP0), terlipressin (Glypressin®) will be administered as a 1 mg bolus over 2 minutes, followed by a continuous infusion at 2 mcg/kg/hour.

Direct portal measurements will be done at the time points explained in the study description.

Intraoperative ultrasound (GE Healthcare®, linear probe) will be used to record arterial and portal flow parameters. Hemodynamic data will be collected during all measurements. The study drug will be infused continuously for at least 24 hours, and up to 5 days if portal pressure remains elevated.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Patients scheduled for right lobe living donor liver transplantation with clinically significant portal hypertension (esophageal varices, thrombocytopenia (<100,000), ascites, encephalopathy; Child-Turcotte-Pugh class B-C)

Exclusion Criteria

• Allergy to any of the medications to be used
• Portal vein thrombosis
• Being treated with terlipressin with a diagnosis of hepatorenal syndrome
• Portopulmonary hypertension
• Acute on chronic liver failure
• Chronic renal failure (glomerular filtration rate ≤ 30%)
• Myocardial ischemia
• Uncontrolled hypertension
• Arrhythmia
• Multiple solid organ transplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istanbul Medipol University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ayse Ince

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

ayşe ince

Role: PRINCIPAL_INVESTIGATOR

Istanbul Medipol University Medipol Mega Hospital

Central Contacts

ayse ince, assist prof

Role: CONTACT

Phone: +905366774988

Email: drayseince@gmail.com

pelin karaaslan, prof

Role: CONTACT

Phone: +905057657550

Email: drpelinsesli@hotmail.com

References

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Reference Type: BACKGROUND

PMID: 31200638 (View on PubMed)

Li XL, Zhu XD, Xiao N, Liu XF, Xu B, Shi GM, Huang C, Shen YH, Cai JB, Zhou J, Fan J, Sun HC. A prospective study of the effect of terlipressin on portal vein pressure and clinical outcomes after hepatectomy: A pilot study. Surgery. 2020 Jun;167(6):926-932. doi: 10.1016/j.surg.2020.01.013. Epub 2020 Feb 26.

Reference Type: BACKGROUND

PMID: 32113581 (View on PubMed)

Papaluca T, Gow P. Terlipressin: Current and emerging indications in chronic liver disease. J Gastroenterol Hepatol. 2018 Mar;33(3):591-598. doi: 10.1111/jgh.14009.

Reference Type: BACKGROUND

PMID: 28981166 (View on PubMed)

Abraldes JG, Bosch J. Somatostatin and analogues in portal hypertension. Hepatology. 2002 Jun;35(6):1305-12. doi: 10.1053/jhep.2002.33469. No abstract available.

Reference Type: BACKGROUND

PMID: 12029614 (View on PubMed)

Lizaola-Mayo B, Vargas HE. Hepatorenal Syndrome-Acute Kidney Injury in Liver Transplantation. Clin Gastroenterol Hepatol. 2023 Sep;21(10S):S20-S26. doi: 10.1016/j.cgh.2023.06.010.

Reference Type: BACKGROUND

PMID: 37625863 (View on PubMed)

Iwakiri Y. Pathophysiology of portal hypertension. Clin Liver Dis. 2014 May;18(2):281-91. doi: 10.1016/j.cld.2013.12.001. Epub 2014 Feb 25.

Reference Type: BACKGROUND

PMID: 24679494 (View on PubMed)

Giabicani M, Joly P, Sigaut S, Timsit C, Devauchelle P, Dondero F, Durand F, Froissant PA, Lamamri M, Payance A, Restoux A, Roux O, Thibault-Sogorb T, Valainathan SR, Lesurtel M, Rautou PE, Weiss E. Predictive role of hepatic venous pressure gradient in bleeding events among patients with cirrhosis undergoing orthotopic liver transplantation. JHEP Rep. 2024 Feb 28;6(6):101051. doi: 10.1016/j.jhepr.2024.101051. eCollection 2024 Jun.

Reference Type: BACKGROUND

PMID: 38699073 (View on PubMed)

Other Identifiers

Medipol Hospital 6

Identifier Type: -

Identifier Source: org_study_id