Mechanism and the Effect of Midodrine on Portal Pressures in Patients With Cirrhosis

NCT01331785 | Withdrawn DMC

• 1 other identifier: ACG-CR-026-2010
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Ascites is a frequent complication of patients with portal hypertension. As portal hypertension progresses, a percentage of these patients develop refractory ascites. Management options at that point include either TIPS or intermittent large volume paracentesis (LVP), with its attendant risks, Portal hypertension is accompanied by systemic circulatory dysfunction (decreased systemic vascular resistance and systolic BP), which is exacerbated by large volume paracentesis, with resultant renal and cardiac dysfunction. There are limited options for managing patients with acute decompensation, such as hepatorenal syndrome, although midodrine and other vasoconstrictors have been used in such patients. Midodrine has not been used as a possible therapeutic for ascites. Midodrine however, has been found to change the hemodynamics related to portal hypertension and ascites. There has been also change in mediators related to renal and circulation in studies of short duration (7 days) but not found in studies of 1 month duration, however the clinical effects of midodrine is found for longer duration in other similar conditions. The purpose of the study is to assess the utility of midodrine in patients with obvious systemic circulatory dysfunction (hypotension) in improving the outcome of patients with refractory ascites and change in hemodynamic parameters and its mediators. Specific endpoints include: 1\) an objective reduction of the volume/rate of accumulation of ascites and 2) a decrease in the frequency of LVP.

Conditions

Cirrhosis; End Stage Liver Disease; Ascites; Hypotension

Keywords

paracentesis; ascites; hypotension

Outcome Measures

Primary Outcomes (1)

• Volume and frequency of paracentesis and quality of life

  To quantify the volume and rate of production of ascites (as estimated by the frequency of paracentesis) in patients with refractory ascites and hypotension requiring intermittent LVP and comparing these values before and after use of midodrine.

  3 months of study drug

Secondary Outcomes (1)

• Renal and cardiovascular hemodynamic changes

  3 months

Study Arms (1)

Midodrine

EXPERIMENTAL

Drug: Midodrine

Interventions

Midodrine DRUG

Midodrine 2.5 mg to 10 mg three times a day to increase systolic BP above 100 mmHgor by 10 mmHg

Midodrine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years old
• Evidence of ESLD and ascites
• Ascites requiring periodic large volume paracentesis (1+ / month) of more than 3 months duration
• Systolic BP \< 100 mmHg

You may not qualify if:

• Prior liver transplant
• Evaluated for multiple organ transplant
• Malignancies
• Non cirrhotic causes of ascites
• Prior TIPS usage (transjugular intrahepatic porto-systemic shunt)
• Primary renal diseases
• Chronic kidney disease (CKD) \>=4
• Grade 3 or 4 encephalopathy
• Child C cirrhosis or model for end stage liver disease (MELD) \> 20
• Patients requiring large volume paracentesis for more than 12 months
• Frequency of paracentesis less than 6 in the preceding 3 months
• Active recreational drug and alcohol usage

Sponsors & Collaborators

• The Cleveland Clinic: lead
• American College of Gastroenterology: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Fibrosis; End Stage Liver Disease; Ascites; Hypotension

Interventions

Midodrine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Achuthan Sourianarayanane

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2011
• First Posted: April 8, 2011
• Study Start: April 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 31, 2013

Record last verified: 2011-04

Locations

US (1)