Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome - Full Text View

Sponsored by:	University of Padova
Information provided by:	University of Padova
ClinicalTrials.gov Identifier:	NCT00742339

Purpose

From 1999, several studies have showed that the use of vasoconstrictors in association with albumin are effective in the treatment of hepatorenal syndrome (HRS). The rationale of the use of vasoconstrictors together with albumin in the treatment of this severe complication of portal hypertension in patients with cirrhosis is to correct the reduction of the effective circulating volume due to the splanchnic arterial vasodilatation.In most of these studies terlipressin, a derivate of vasopressin, has been used as vasoconstrictor as intravenous boluses moving from an initial dose of 0.5-1 mg/4 hr. In some studies midodrine, an alpha-adrenergic agonist, given by mouth has been used as vasoconstrictor at a dose ranging from 2.5 up to 12.5 tid together with octreotide, an inhibitor of the release of glucagon, given subcutaneously at a dose ranging from 10 µg upt to 200 µg tid. To the day, there isn't a study comparing terlipressin + albumin versus midodrine + octreotide + albumin in the treatment of HRS in patients with cirrhosis.Thus, the aim of the study is to compare terlipressin + albumin vs midodrine + octreotide + albumin in the treatment of the HRS in patients with cirrhosis.

Condition	Intervention	Phase
Cirrhosis Hepatorenal Syndrome	Drug: Terlipressin plus albumin Drug: Midodrine plus octreotide plus human albumin	Phase II Phase III

MedlinePlus related topics: Cirrhosis

Drug Information available for: Octreotide Octreotide acetate Creatinine Midodrine Midodrine hydrochloride Terlipressin Benzocaine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome (HRS): An Open Multicentric Randomized Study

Further study details as provided by University of Padova:

Primary Outcome Measures:

The primary end-point of the study is the complete reform of the renal function (serum creatinine < 1.5 mg/dl. The primary end point will be evaluated at the end of the treatment. [ Time Frame: The treatment will be continued for a maximum of 15 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	May 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Fifty patients with cirrhosis and HRS will be randomly assigned to arm 1.	Drug: Terlipressin plus albumin The terlipressin will be give at the initial dose of 3 mg/24 hours by intravenous continuous infusion. If during the following 48 hours the serum value of creatinine will not change or will go down less than 25%, the dose of terlipressin will be increased to 6 mg/24 hours. If no response will ensue, the dose of terlipressin will be increased to the maximal dose of 12 mg/24 hours. Twenty percent human albumin solution will be administrate together with terlipressin at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days.
2: Experimental Fifty patients with cirrhosis and HRS will be randomly assigned to arm 2.	Drug: Midodrine plus octreotide plus human albumin Midodrine will be give orally at the initial dose 7.5 tid together with octreotide at the initial dosage of 100 µg subcutaneously tid. If during the following 96 hours the serum value of creatinine will not change or will go down less than 25%, the dose of midodrine will be increased to 12.5 mg tid Twenty percent human albumin solution will be administrate together with midodrine and octreotide at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days.

Arms

Assigned Interventions

1: Active Comparator

Fifty patients with cirrhosis and HRS will be randomly assigned to arm 1.

Drug: Terlipressin plus albumin

The terlipressin will be give at the initial dose of 3 mg/24 hours by intravenous continuous infusion. If during the following 48 hours the serum value of creatinine will not change or will go down less than 25%, the dose of terlipressin will be increased to 6 mg/24 hours. If no response will ensue, the dose of terlipressin will be increased to the maximal dose of 12 mg/24 hours. Twenty percent human albumin solution will be administrate together with terlipressin at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days.

2: Experimental

Fifty patients with cirrhosis and HRS will be randomly assigned to arm 2.

Drug: Midodrine plus octreotide plus human albumin

Midodrine will be give orally at the initial dose 7.5 tid together with octreotide at the initial dosage of 100 µg subcutaneously tid. If during the following 96 hours the serum value of creatinine will not change or will go down less than 25%, the dose of midodrine will be increased to 12.5 mg tid Twenty percent human albumin solution will be administrate together with midodrine and octreotide at the dosage of 1 g/Kg of body weight, on first day, and then, to the dosage of 20-40 g/Kg in order to maintain the central venous pressure (CVP) between 10 and 15 cm H2O.The treatment with terlipressin and albumin will be maintained for 24 hours after complete or incomplete resolution. The length of the study in patients with complete and incomplete resolution will reach a maximum of 15 days. In the patients without response the treatment with the high dosage of terlipressin will go on for a maximum of 7 days.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with cirrhosis and diagnosis of HRS type 1 or 2,serum creatinine > 2.5 mg/dl

Exclusion Criteria:

Diagnosis of HCC with a staging beyond the Milan Criteria di Milano
Septic shock (systolic arterial pressure < 90 mmHg
Significant heart or respiratory failure
Peripheral arteriophaty clinically significant
Previous heart stroke or significant alteration of the ECG

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00742339

Contacts

Contact: Paolo Angeli, Md, PhD

+390498218676

pangeli@unipd.it

Locations

Italy
Dept. of Clinical and Experimental Medicine, University of Padova	Recruiting
Padova, Italy, 35100
Sub-Investigator: Silvano Fasolato, MD

Sponsors and Collaborators

University of Padova

More Information

Publications of Results:

Salerno F, Gerbes A, Ginès P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. Epub 2007 Mar 27. Review. No abstract available.

Responsible Party:	Dept. of Clinical and Experimental Medicine, University of Padova, Italy ( Paolo Angeli, MD, PhD )
Study ID Numbers:	1264P
Study First Received:	August 26, 2008
Last Updated:	August 26, 2008
ClinicalTrials.gov Identifier:	NCT00742339
Health Authority:	Italy: Ministry of Health

Keywords provided by University of Padova:

cirrhosis
hepatorenal syndrome
terlipressin
midodrine
octreotide

human albumin
effective circulating volume
The criteria which will be used for the diagnosis of HRS will be the criteria which were recently published by the International Ascites Club
Patients with cirrhosis and type 2 HRS only with serum creatinine value > 2.5 mg/dl
All patients with cirrhosis and type 1 HRS

Study placed in the following topic categories:

Lysine Vasopressin
Liver Diseases
Fibrosis
Benzocaine
Octreotide
Liver Cirrhosis
Arginine Vasopressin
Hepatorenal syndrome

Digestive System Diseases
Urologic Diseases
Ascites
Terlipressin
Vasopressins
Midodrine
Kidney Diseases
Hepatorenal Syndrome

Additional relevant MeSH terms:

Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Coagulants
Antineoplastic Agents
Physiological Effects of Drugs
Hematologic Agents
Adrenergic Agonists
Pathologic Processes
Syndrome
Therapeutic Uses
Vasoconstrictor Agents
Adrenergic alpha-Agonists

Disease
Antineoplastic Agents, Hormonal
Sympathomimetics
Gastrointestinal Agents
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions
Hemostatics
Autonomic Agents
Natriuretic Agents
Peripheral Nervous System Agents
Antidiuretic Agents

ClinicalTrials.gov processed this record on January 16, 2009