Terlipressin Administration in Patients Undergoing Major Liver Resection

Study Overview
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Brief Summary
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This study investigates if the administration of terlipressin reduces complications after major liver surgery.

Detailed Description
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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

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

Conditions
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Liver Resection, Liver Failure

Intervention / Treatment
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* Drug: Terlipressin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Terlipressin<br>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<br>* 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).<br>|
| Placebo Comparator: NaCl<br>Placebo (Saline 100 ml) administered every 6 hours (total duration of drug administration 120 hours). | Drug: Placebo<br>* Placebo (Saline 100 ml) administered every 6 hours (total duration of drug administration 120 hours).<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |