Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome

NCT00742339 | Terminated Phase 2

• 1 other identifier: 1264P
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cirrhosis; Hepatorenal Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  The treatment will be continued for a maximum of 15 days

Study Arms (2)

1

ACTIVE COMPARATOR

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

Drug: Terlipressin plus albumin

2

EXPERIMENTAL

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

Drug: Midodrine plus octreotide plus human albumin

Interventions

Terlipressin plus albumin DRUG

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.

1

Midodrine plus octreotide plus human albumin DRUG

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.

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

Dept. of Clinical and Experimental Medicine, University of Padova

Padua, 35100, Italy

Location

Related Publications (1)

• Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8. doi: 10.1136/gut.2006.107789. Epub 2007 Mar 27. No abstract available.

  PMID: 17389705 BACKGROUND

MeSH Terms

Conditions

Fibrosis; Hepatorenal Syndrome

Interventions

Terlipressin; Albumins; Midodrine; Octreotide; Serum Albumin, Human

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Serum Albumin; Blood Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 26, 2008
• First Posted: August 27, 2008
• Study Start: May 1, 2005
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

IT (1)