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

• Status: Withdrawn
• Trial end date: 2012-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Cleveland Clinic
• Collaborator: American College of Gastroenterology
• Treatments: Midodrine

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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