Study to Evaluate if the Drug Vasopressin Protects the Kidneys for Patients Undergoing Liver Transplant

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is evaluate the medication vasopressin for its ability to preserve kidney function in patients undergoing liver transplantation.

Detailed Description
-----------------
Renal failure is a common complication of liver disease. Hepatorenal syndrome is caused by a dysfunctional global circulation in the setting of liver disease: Increased flow to the mesenteric circulation is a contributor to decreased blood flow to the kidneys (1). Renal failure often worsens in the perioperative period of liver transplantation since the kidneys are further stressed by reduced flow due to inferior venacava occlusion, decreased blood flow to the kidneys from anesthetics, as well as hypotension from volume shifts, such as when large volumes of ascites are removed. Renal failure is a cause of major morbidity and mortality in patients undergoing liver transplantation. Vasopressin is a logical choice of therapy in this context as the effects of the drug work to particularly increase renal blood flow and glomerular filtration rate due to the location of specific vasopressin receptors within the renal vasculature. It has been suggested that the use of splanchnic (and systemic) vasoconstrictors such as terlipressin (a vasopressin analog) or alpha-1-adrenoceptor agonists (midodrine or noradrenaline) may improve renal function in patients with type 1 Hepatorenal Syndrome. Six studies (with only one randomized study in a small series of patients) have shown that terlipressin improves renal function in these patients (2-7). This drug is available in Europe, but not in the United States. However, while anesthesiologists commonly use vasopressin during liver transplantation in the setting of hepatorenal syndrome or vasodilatory shock, the validity of this practice for its effects on renal function and outcomes has not been rigorously studied (8-10). Therefore, the purpose of this study is to evaluate the effects of low-dose vasopressin on intraoperative and perioperative renal function in liver transplant patients. This study will be a randomized, double-blind controlled trial performed in adult liver transplant patients coming to surgery for chronic liver disease; the major end-points of analyses are renal function tests in the perioperative period.

Official Title
-----------------
Low Dose Vasopressin for Renal Protection During Liver Transplantation

Conditions
-----------------
Liver Failure

Intervention / Treatment
-----------------
* Drug: Vasopressin
* Drug: Normal saline placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: > 18 years of age undergoing liver transplant ability to provide informed consent. If patient is unable to give informed consent i.e. hepatic encephalopathy, consent may be obtained from the patient's legally authorized representative Exclusion Criteria: < 18 years of age renal failure

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vasopressin<br> | Drug: Vasopressin<br>* Patients randomly assigned to the experimental arm of the study will receive vasopressin 0.5U/hr IV (20 U vasopressin in 250mL of 0.9% NaCL to infuse at a rate of 6.25mL/hr) via internal jugular catheter. Vasopressin infusion is started at the time of incision and is stopped at the time abdominal closure is completed<br>|
| Placebo Comparator: Normal saline placebo<br> | Drug: Normal saline placebo<br>* Patients randomly assigned to the placebo arm of the study will receive placebo (0.9% NaCl to infuse at a rate of 6.25 mL/hr) via internal jugular catheter<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Creatinine Levels |  | baseline to 48 hours postop | 
| Change in Urine Output |  | 24 hours to 48 hours postop | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Participants Who Needed Diuretics Postoperatively |  | 48 hours | 
| Count of Patient Who Need Vasopressers in the Perioperative Period |  | 48 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
liver transplantation, vasopressin, renal function, hypotension, creatinine, urine output, diuretics, vasopressors, hemodynamic stability