Alternatives to Large Volume Paracentesis Study - Full Text View

Sponsors and Collaborators:	VA Connecticut Healthcare System Yale University
Information provided by:	VA Connecticut Healthcare System
ClinicalTrials.gov Identifier:	NCT00530959

Purpose

The overall objective of this proposal is to compare the effect of a combination of vasoconstrictors (midodrine + octreotide) to albumin on the time to recurrence of ascites in patients with refractory ascites treated with large volume paracentesis (LVP). This objective will be achieved through a prospective, randomized, double blind, placebo-controlled clinical trial.

Primary Aim

Investigate the effect of LVP plus a combination of vasoconstrictors (octreotide + midodrine), compared to LVP +ALB on time to recurrence of ascites in cirrhotic patients with refractory ascites.

Secondary Aims
Investigate the rate of development of post-paracentesis circulatory dysfunction (PCD) in patients treated with LVP + vasoconstrictors and compare it to the rate obtained with LVP+ALB
Correlate changes in forearm blood flow (FBF) and MAP with time to recurrence of ascites and development of PCD.
Investigate the effect of LVP + vasoconstrictors compared to LVP+ALB on time to development of hepatorenal syndrome (HRS) or death.

Condition	Intervention
Cirrhosis	Drug: midodrine and octreotide

MedlinePlus related topics: Cirrhosis

Drug Information available for: Octreotide Octreotide acetate Midodrine Midodrine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study
Official Title:	Vasoconstrictors as Alternatives to Albumin After Large Volume Paracentesis Large Volume Paracentesis (LVP) in Cirrhosis

Further study details as provided by VA Connecticut Healthcare System:

Primary Outcome Measures:

The analysis of the primary endpoint, time to recurrence of ascites, will be according to the principle of intention-to-treat. The primary treatment comparison will be patients randomized to LVP + vasoconstrictors vs LVP + albumin. [ Time Frame: time to recurrence ] [ Designated as safety issue: No ]

Estimated Enrollment:	104
Study Start Date:	August 2003
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Intervention Details:

After randomization and performance of LVP, patients will be instructed to continue midodrine (or midodrine placebo) at a dose of 10 mg orally three times a day.At each monthly visit a total of 2 intramuscular injections, a month apart, of octreotide-LAR (or octreotide placebo) at a dose of 20 mg will be administered.

Detailed Description:

We hypothesize that vasoconstrictors can be used as an alternative to albumin after LVP in cirrhotic patients with refractory ascites (i.e. the use of vasoconstrictors will lead to an equal or lower rate of PCD). Unlike albumin, the advantage of vasoconstrictors is that they can be administered for a longer period of time and therefore their effect on effective arterial blood volume would be more sustained and result, not only in prevention of PCD, but also in the prevention of sodium retention and therefore in a delay in the reaccumulation of ascites. Additionally, peripheral vasodilatation and activation of renal vasoconstrictive systems have been shown to lead to renal dysfunction and to be of prognostic importance in cirrhosis, specifically, a low mean arterial blood pressure (a measure of peripheral vasodilatation) and increased PRA and angiotensin (a measure of activated renal vasoconstrictive systems) have been shown to be independent predictors of survival in cirrhosis [3]. Therefore, a sustained amelioration in vasodilatation (with consequent reduction in renal vasoconstrictive systems) could potentially lead to a reduction in the rate of renal dysfunction and to an improvement in survival.

Primary hypothesis:

Patients randomized to LVP + vasoconstrictors will have a significantly longer time to recurrence of ascites compared to patients randomized to LVP+ALB

Secondary hypotheses:

The development of post-paracentesis circulatory dysfunction or PCD (defined as an increase in PRA by >50% from baseline to a level > 4 ng/mL.h at post-paracentesis day 6) will be comparable in patients randomized to LVP + vasoconstrictors compared to patients randomized to LVP + ALB.
Recurrence of ascites and development of PCD will be related to changes in the state of peripheral vasodilatation as assessed by measurements of mean arterial pressure (MAP) and forearm blood flow (FBF)
Patients randomized to LVP + vasoconstrictors will have a significantly longer time to the development of hepatorenal syndrome (HRS) or death compared to those randomized to LVP + ALB

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Cirrhosis of any etiology, diagnosed on firm clinical grounds or by liver biopsy. Alcoholic cirrhosis will be defined as cirrhosis in a patient with a >5-year history of alcohol ingestion that exceeds 40 g/day (females) or 60 g/day (males). All other cirrhotic patients will be considered non-alcoholic cirrhotics and their etiology will have been established by results of routinely used tests, i.e. hepatitis B and C serological markers, autoimmune markers, iron studies, ferritin, copper, ceruloplasmin, alpha-1-antitrypsin, antimitochondrial antibodies, etc. Alcoholic patients in whom anti-HCV and HBsAg is positive will be analyzed in the alcoholic etiology group if the most recent alcohol ingestion is <6 months
Age between 18 and 80 years
Presence of moderate to severe ascites that requires large-volume paracentesis and the estimated amount of fluid to be removed is greater than 5 liters
Informed, written consent
Absence of exclusion criteria listed below

Exclusion Criteria:

Patients with small amounts of ascites or ascites only detectable by ultrasound
Patients with severe hepatic hydrothorax and no ascites or only small amounts of ascites
Recent gastrointestinal hemorrhage (within one month)
Active bacterial infection
Cardiac failure
Findings suggestive of organic renal disease, as defined by 2+ or 3+ proteinuria, any hematuria or abnormal renal ultrasound. Patients with trace or 1+ proteinuria will be excluded only if the abnormality is present in two separate urine samples.
Hepatocellular carcinoma
Severe co-morbidity that would affect short-term prognosis (e.g. advanced neoplasia)
Serum creatinine >3 mg/dL
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530959

Contacts

Contact: Guadalupe Garcia-Tsao, MD

203-932-5711 ext 2207

guadalupe.garcia-tsao@yale.edu

Locations

United States, Connecticut
VA Connecticut Healthcare System	Recruiting
West Haven, Connecticut, United States, 06516
Contact: Guadalupe Garcia-Tsao, MD 203-932-5711 ext 2207 guadalupe.garcia-tsao@yale.edu
Contact: Irteza Inayat, MD 203-932-5711 ext 5336 irteza.inayat@yale.edu
Principal Investigator: Guadalupe Garcia-Tsao, MD

Sponsors and Collaborators

VA Connecticut Healthcare System

Yale University

Investigators

Principal Investigator:

Guadalupe Garcia-Tsao, MD

Yale University

More Information

Responsible Party:	VA Connecticut Healthcare System ( Guadalupe Garcia-Tsao, MD, Principal Investigator )
Study ID Numbers:	LG0017
Study First Received:	September 16, 2007
Last Updated:	January 24, 2009
ClinicalTrials.gov Identifier:	NCT00530959
Health Authority:	United States: Federal Government; United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by VA Connecticut Healthcare System:

refractory ascites
LVP and Albumin
LVP and vasoconstrictors
recurrent ascites

Study placed in the following topic categories:

Liver Diseases
Digestive System Diseases
Fibrosis
Ascites

Midodrine
Octreotide
Liver Cirrhosis
Recurrence

Additional relevant MeSH terms:

Neurotransmitter Agents
Adrenergic alpha-Agonists
Antineoplastic Agents, Hormonal
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Sympathomimetics
Physiological Effects of Drugs
Gastrointestinal Agents

Cardiovascular Agents
Adrenergic Agonists
Pharmacologic Actions
Pathologic Processes
Autonomic Agents
Therapeutic Uses
Vasoconstrictor Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on February 06, 2009