Vasoconstrictors as Alternatives to Albumin After Large-Volume Paracentesis (LVP) in Cirrhosis

Phase 4

Completed

Conditions: Ascites
Cirrhosis

Interventions: Drug: Intravenous Saline Infusion (Albumin placebo)
Drug: Albumin
Drug: Oral tablet (Midodrine placebo)
Drug: Midodrine
Drug: Saline injection (Octreotide LAR placebo)
Drug: Octreotide LAR
Procedure: Large Volume Paracentesis

Registration Number: NCT00108355

Lead Sponsor: US Department of Veterans Affairs

Brief Summary: This clinical trial compares a combination of two drugs that constrict blood vessels (Octreotide LAR and Midodrine) to albumin after large volume paracentesis. Subjects have cirrhosis and ascites.

Detailed Description: This prospective, placebo-controlled, randomized, clinical trial compares the effect of a combination of vasoconstrictors (octreotide plus midodrine) to albumin on the time to recurrence of ascites in patients with refractory ascites treated with large volume paracentesis. The treatment allocation ratio for the two treatment arms is 1:1 using a stratified random permuted block design. Subjects are patients 18-80 years old with cirrhosis and ascites who are stratified according to the presence or absence of renal dysfunction at the time of randomization. Measurements include blood pressure, weight, girth, abdominal ultrasound, forearm blood flow, plasma renin activity, angiotensin, and aldosterone, repeated during a 6 month period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Cirrhosis of any etiology
Age 18-80 years
Moderate to severe ascites

Exclusion Criteria

No or small ascites
Severe hepatic hydrothorax
Recent GI (gastrointestinal) hemorrhage
Active bacterial infection
Cardiac failure
Organic renal disease
Hepatocellular carcinoma
Severe comorbidity (advanced neoplasia)
Serum creatinine > 3 mg/dl
Pregnancy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vasoconstrictor (Study Group)	Intravenous Saline Infusion (Albumin placebo)	After LVP, patients in this group received: Octreotide LAR intramuscular injection 20 mg, every 30 days; Midodrine tablet, 10 mg three times a day; Intravenous saline infusion (Albumin placebo), one time dose
Albumin (Control group)	Albumin	After LVP, patients in this group received: Intravenous albumin (25%) at 8 g/liter of ascitic fluid removed, one time dose; Intramuscular injection of 5 cc saline (Octreotide LAR placebo), every 30 days ; Oral tablet 3 times a day (Midodrine placebo)
Albumin (Control group)	Oral tablet (Midodrine placebo)	After LVP, patients in this group received: Intravenous albumin (25%) at 8 g/liter of ascitic fluid removed, one time dose; Intramuscular injection of 5 cc saline (Octreotide LAR placebo), every 30 days ; Oral tablet 3 times a day (Midodrine placebo)
Albumin (Control group)	Saline injection (Octreotide LAR placebo)	After LVP, patients in this group received: Intravenous albumin (25%) at 8 g/liter of ascitic fluid removed, one time dose; Intramuscular injection of 5 cc saline (Octreotide LAR placebo), every 30 days ; Oral tablet 3 times a day (Midodrine placebo)
Albumin (Control group)	Large Volume Paracentesis	After LVP, patients in this group received: Intravenous albumin (25%) at 8 g/liter of ascitic fluid removed, one time dose; Intramuscular injection of 5 cc saline (Octreotide LAR placebo), every 30 days ; Oral tablet 3 times a day (Midodrine placebo)
Vasoconstrictor (Study Group)	Midodrine	After LVP, patients in this group received: Octreotide LAR intramuscular injection 20 mg, every 30 days; Midodrine tablet, 10 mg three times a day; Intravenous saline infusion (Albumin placebo), one time dose
Vasoconstrictor (Study Group)	Large Volume Paracentesis	After LVP, patients in this group received: Octreotide LAR intramuscular injection 20 mg, every 30 days; Midodrine tablet, 10 mg three times a day; Intravenous saline infusion (Albumin placebo), one time dose
Vasoconstrictor (Study Group)	Octreotide LAR	After LVP, patients in this group received: Octreotide LAR intramuscular injection 20 mg, every 30 days; Midodrine tablet, 10 mg three times a day; Intravenous saline infusion (Albumin placebo), one time dose

Primary Outcome Measures

Name	Time	Method
Time to Recurrence of Ascites.	Variable depending on the patient, average 10 days	Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group)

Secondary Outcome Measures

Name	Time	Method
Development of Post-paracentesis Circulatory Dysfunction (PCD)	6 days after paracentesis	Defined as an increase in Plasma Renin Activity (PRA) by \>50% from baseline to a level \> 4 ng/mL/h at post-paracentesis day