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

NCT ID: NCT00886262

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2011-08-31

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.

Conditions

Liver Failure

Study Design

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

Study Groups

Vasopressin

Group Type: EXPERIMENTAL

Vasopressin

Intervention Type: DRUG

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

Normal saline placebo

Group Type: PLACEBO_COMPARATOR

Normal saline placebo

Intervention Type: DRUG

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

Interventions

Vasopressin

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

Normal saline placebo

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Emory University

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Matthew D McEvoy, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Scott T Reeves, MD

Role: STUDY_CHAIR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 16496352 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10905585 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11322061 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11910344 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11981339 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12297842 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12542598 (View on PubMed)

Csete M. IARS 2007 Review Course Lectures: Anesthesia for Liver Transplantation. Anes Analg 2007; 104:19-24,2007.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 16790680 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16534358 (View on PubMed)

Other Identifiers

Vasopressin HR #17345

Identifier Type: -

Identifier Source: org_study_id