Terlipressin Administration in Patients Undergoing Major Liver Resection

Terlipressin Administration in Patients Undergoing Major Liver Resection: a Prospective Randomized Blinded Trial

This study investigates if the administration of terlipressin reduces complications after major liver surgery.

Study Overview

• Status: Terminated
• Conditions: Liver Failure; Liver Resection
• Intervention / Treatment: Drug: Terlipressin; Drug: Placebo

Detailed Description

Background

Surgery offers the only potential cure in many patients with primary or metastatic liver cancer. Extending the limits and improving safety of liver resection would allow more patients to benefit from surgery and to increase their survival. The prerequisite for successful and safe liver surgery is the optimal regeneration of the remaining hepatic tissue in order to fulfill the metabolic demands of the patient. Liver regeneration depends on a correct portal pressure and portal blood flow. In the preliminary results the investigators show an elevation of portal pressure post partial hepatectomy in mice. Pharmacologic reduction of such elevated portal pressure using terlipressin, a vasopressin agonist, was associated with improved liver regeneration.

Objective

Surgery offers the only potential cure in many patients with primary or metastatic liver cancer. Extending the limits and improving safety of liver resection would allow more patients to benefit from surgery and to increase their survival. Liver regeneration depends on a correct portal pressure and portal blood flow. Pharmacologic reduction of elevated portal pressure using terlipressin, a vasopressin agonist, is potentially associated with improved liver regeneration. Aim: To perform a prospective randomized trial comparing terlipressin versus placebo in patients undergoing major hepatic resection.

Methods

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Berne, Switzerland, 3010
    • Dep. of Visceral Surgery, University Hospital Berne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing resection of 3 or more liver segments
• Minimum age of 18
• Any gender
• Written informed consent

Exclusion Criteria

• Preoperative renal failure (GFR < 50ml/min)
• Severe liver dysfunction (Child-Turcotte-Pugh grade C)
• Hyponatremia (<132mmol/l)
• Severe aortic regurgitation, severe mitral regurgitation, heart failure
• Symptomatic coronary heart disease
• Bradycardic arrhythmia (heart rate < 60/min)
• Peripheral artery occlusive disease (clinical stadium II-IV)
• Dilatative arteriopathy, history of subarachnoidal bleeding
• Decompensated arterial hypertension (Blood pressure >160/100mmHg despite intensive treatment)
• Present or suspected acute mesenteric ischemia
• Septic shock
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Terlipressin; Terlipressin given as intravenous injections of 1mg iv in 100ml of NaCl every 6 hours (total duration of drug administration 120 hours, cumulative dose is 20mg).	Drug: Terlipressin; Terlipressin given as intravenous injections of 1mg iv in 100ml of NaCl every 6 hours (total duration of drug administration 120 hours, cumulative dose is 20mg).
PLACEBO_COMPARATOR: NaCl; Placebo (Saline 100 ml) administered every 6 hours (total duration of drug administration 120 hours).	Drug: Placebo; Placebo (Saline 100 ml) administered every 6 hours (total duration of drug administration 120 hours).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with incident of a composite end point	one month

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with pleural effusion	one month
Number of patients with surgical site infection	one month
Number of patients with sepsis	one month
Number of patients with pneumonia	one month
Number of patients with intraabdominal hematoma	one month
Number of patients with acute renal failure	one month
Number of patients with blood transfusion	one month

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Guido Beldi, Professor Dr. med., University of Bern

Publications and helpful links

General Publications

• Kohler A, Perrodin S, De Gottardi A, Candinas D, Beldi G. Effectiveness of terlipressin for prevention of complications after major liver resection - A randomized placebo-controlled trial. HPB (Oxford). 2020 Jun;22(6):884-891. doi: 10.1016/j.hpb.2019.10.011. Epub 2019 Oct 31.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): March 1, 2018
• Study Completion (ACTUAL): March 1, 2018

Study Registration Dates

• First Submitted: August 9, 2013
• First Submitted That Met QC Criteria: August 9, 2013
• First Posted (ESTIMATE): August 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: 190/11