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

• ClinicalTrials.gov Identifier: NCT00742339
• Recruitment Status: Terminated
• First Posted: August 27, 2008
• Last Update Posted: October 15, 2014
• Sponsor: University of Padova
• Information provided by: University of Padova

Tracking Information

• First Submitted Date: August 26, 2008
• First Posted Date: August 27, 2008
• Last Update Posted Date: October 15, 2014
• Study Start Date: May 2005
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 26, 2008): 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 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome
• Official Title: Terlipressin + Albumin Versus Midodrine + Octreotide in the Treatment of Hepatorenal Syndrome (HRS): An Open Multicentric Randomized Study
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cirrhosis
• Hepatorenal Syndrome

Intervention

• 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.
• 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.

Study Arms

• Active Comparator: 1
  Fifty patients with cirrhosis and HRS will be randomly assigned to arm 1.
  Intervention: Drug: Terlipressin plus albumin
• Experimental: 2
  Fifty patients with cirrhosis and HRS will be randomly assigned to arm 2.
  Intervention: Drug: Midodrine plus octreotide plus human albumin

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 11, 2014): 49
• Original Estimated Enrollment (submitted: August 26, 2008): 100
• Actual Study Completion Date: October 2013
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT00742339
• Other Study ID Numbers: 1264P
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Paolo Angeli, MD, PhD, Dept. of Clinical and Experimental Medicine, University of Padova, Italy
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Padova
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Padova
• Verification Date: October 2014