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

Primary Purpose

Liver Failure

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vasopressin
Normal saline placebo
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Failure focused on measuring liver transplantation, vasopressin, renal function, hypotension, creatinine, urine output, diuretics, vasopressors, hemodynamic stability

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Vasopressin

Normal saline placebo

Arm Description

Outcomes

Primary Outcome Measures

Change in Creatinine Levels
Change in Urine Output

Secondary Outcome Measures

Count of Participants Who Needed Diuretics Postoperatively
Count of Patient Who Need Vasopressers in the Perioperative Period

Full Information

First Posted
April 21, 2009
Last Updated
September 21, 2018
Sponsor
Medical University of South Carolina
Collaborators
Emory University
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1. Study Identification

Unique Protocol Identification Number
NCT00886262
Brief Title
Study to Evaluate if the Drug Vasopressin Protects the Kidneys for Patients Undergoing Liver Transplant
Official Title
Low Dose Vasopressin for Renal Protection During Liver Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
July 2007 (Actual)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
Collaborators
Emory University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Failure
Keywords
liver transplantation, vasopressin, renal function, hypotension, creatinine, urine output, diuretics, vasopressors, hemodynamic stability

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vasopressin
Arm Type
Experimental
Arm Title
Normal saline placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Vasopressin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Normal saline placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in Creatinine Levels
Time Frame
baseline to 48 hours postop
Title
Change in Urine Output
Time Frame
24 hours to 48 hours postop
Secondary Outcome Measure Information:
Title
Count of Participants Who Needed Diuretics Postoperatively
Time Frame
48 hours
Title
Count of Patient Who Need Vasopressers in the Perioperative Period
Time Frame
48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew D McEvoy, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Scott T Reeves, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Study Chair
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16496352
Citation
Moreau R, Lebrec D. The use of vasoconstrictors in patients with cirrhosis: type 1 HRS and beyond. Hepatology. 2006 Mar;43(3):385-94. doi: 10.1002/hep.21094.
Results Reference
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PubMed Identifier
10905585
Citation
Uriz J, Gines P, Cardenas A, Sort P, Jimenez W, Salmeron JM, Bataller R, Mas A, Navasa M, Arroyo V, Rodes J. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol. 2000 Jul;33(1):43-8. doi: 10.1016/s0168-8278(00)80158-0.
Results Reference
background
PubMed Identifier
11322061
Citation
Mulkay JP, Louis H, Donckier V, Bourgeois N, Adler M, Deviere J, Le Moine O. Long-term terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study. Acta Gastroenterol Belg. 2001 Jan-Mar;64(1):15-9.
Results Reference
background
PubMed Identifier
11910344
Citation
Moreau R, Durand F, Poynard T, Duhamel C, Cervoni JP, Ichai P, Abergel A, Halimi C, Pauwels M, Bronowicki JP, Giostra E, Fleurot C, Gurnot D, Nouel O, Renard P, Rivoal M, Blanc P, Coumaros D, Ducloux S, Levy S, Pariente A, Perarnau JM, Roche J, Scribe-Outtas M, Valla D, Bernard B, Samuel D, Butel J, Hadengue A, Platek A, Lebrec D, Cadranel JF. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology. 2002 Apr;122(4):923-30. doi: 10.1053/gast.2002.32364.
Results Reference
background
PubMed Identifier
11981339
Citation
Halimi C, Bonnard P, Bernard B, Mathurin P, Mofredj A, di Martino V, Demontis R, Henry-Biabaud E, Fievet P, Opolon P, Poynard T, Cadranel JF. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol. 2002 Feb;14(2):153-8. doi: 10.1097/00042737-200202000-00009.
Results Reference
background
PubMed Identifier
12297842
Citation
Ortega R, Gines P, Uriz J, Cardenas A, Calahorra B, De Las Heras D, Guevara M, Bataller R, Jimenez W, Arroyo V, Rodes J. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology. 2002 Oct;36(4 Pt 1):941-8. doi: 10.1053/jhep.2002.35819.
Results Reference
background
PubMed Identifier
12542598
Citation
Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol. 2003 Feb;18(2):152-6. doi: 10.1046/j.1440-1746.2003.02934.x.
Results Reference
background
Citation
Csete M. IARS 2007 Review Course Lectures: Anesthesia for Liver Transplantation. Anes Analg 2007; 104:19-24,2007.
Results Reference
background
PubMed Identifier
16790680
Citation
Roth JV. The use of vasopressin bolus to treat refractory hypotension secondary to reperfusion during orthotopic liver transplantation. Anesth Analg. 2006 Jul;103(1):261. doi: 10.1213/01.ANE.0000215232.42488.6D. No abstract available.
Results Reference
background
PubMed Identifier
16534358
Citation
De Wolf AM. Preoperative optimization of patients with liver disease. Curr Opin Anaesthesiol. 2005 Jun;18(3):325-31. doi: 10.1097/01.aco.0000169242.03754.cc.
Results Reference
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Study to Evaluate if the Drug Vasopressin Protects the Kidneys for Patients Undergoing Liver Transplant

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