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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Vasoconstrictors as Alternatives to Albumin After Large Volume Paracentesis in Cirrhosis

Conditions
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Ascites, Cirrhosis

Intervention / Treatment
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* Drug: Albumin
* Drug: Intravenous Saline Infusion (Albumin placebo)
* Drug: Midodrine
* Drug: Oral tablet (Midodrine placebo)
* Drug: Octreotide LAR
* Drug: Saline injection (Octreotide LAR placebo)
* Procedure: Large Volume Paracentesis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Albumin (Control group)<br>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) | Drug: Albumin<br>* Intravenous Albumin at a dose of 8g/liter of ascitic fluid removed<br>Drug: Oral tablet (Midodrine placebo)<br>* Oral tablet (Midodrine placebo) three times a day<br>Drug: Saline injection (Octreotide LAR placebo)<br>* Saline intramuscular injection 5 cc every 30 days.<br>Procedure: Large Volume Paracentesis<br>* Procedure to remove large amounts (more than 5 liter) of ascitic fluid via a catheter.<br>* Other names: LVP;|
| Experimental: Vasoconstrictor (Study Group)<br>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 | Drug: Intravenous Saline Infusion (Albumin placebo)<br>* Intravenous saline Infusion (Albumin placebo)<br>Drug: Midodrine<br>* Midodrine oral tablet at 10 mg three times a day.<br>Drug: Octreotide LAR<br>* Octreotide LAR 20 mg intramuscular injection every 30 days<br>Procedure: Large Volume Paracentesis<br>* Procedure to remove large amounts (more than 5 liter) of ascitic fluid via a catheter.<br>* Other names: LVP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Recurrence of Ascites. | Comparison between Albumin (Control group) and Vasoconstrictor (Treatment group) | Variable depending on the patient, average 10 days | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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albumin, ascites, paracentesis