Clinical trial NCT00886262: 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
Overall status: COMPLETED
Phase: NA
Conditions: Liver Failure
Keywords: liver transplantation
vasopressin
renal function
hypotension
creatinine
urine output
diuretics
vasopressors
hemodynamic stability
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Emory University
First posted: 2009-04-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Creatinine Levels
timeFrame: baseline to 48 hours postop
measure: Change in Urine Output
timeFrame: 24 hours to 48 hours postop
Secondary outcomes:
measure: Count of Participants Who Needed Diuretics Postoperatively
timeFrame: 48 hours
measure: Count of Patient Who Need Vasopressers in the Perioperative Period
timeFrame: 48 hours
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Matthew D McEvoy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Scott T Reeves, MD
role: STUDY_CHAIR
References:
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.
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.
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.
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.
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.
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.
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.
citation: Csete M. IARS 2007 Review Course Lectures: Anesthesia for Liver Transplantation. Anes Analg 2007; 104:19-24,2007.
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.
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.