TERAS: Terlipressin in Cirrhotic Patients With Recidivation Ascites Treated With Paracentesis and Albumin

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00986817

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Ascites is a common complication of cirrhosis. Sodium restriction and diuretics are the first step treatment. Refractory ascites (not responding to first step treatment) is treated with repeated large volume paracentesis followed by intra venous albumin expansion. In pilot studies vasoconstrictor agents such as terlipressin have shown beneficial effect on ascites production. Therefore the investigators will study the effect of combined therapy with albumin and terlipressin on recidivation ascites.

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis	Drug: Terlipressin Drug: Placebo	Phase 3

Detailed Description

About 30% of cirrhotic patients will develop ascites. Sodium restriction and diuretics are the first step treatment. Total paracentesis is used in patients with cirrhosis and tense ascites. Paracentesis alone was found to induce a decrease in effective arterial blood volume. This circulatory dysfunction may induce inhospital complications such as impaired renal function or hyponatremia and is associated with a significant reduction in long term survival. Intravenous albumin administration after paracentesis has been shown to prevent the post paracentesis decrease in arterial blood volume. Paracentesis also induces arteriolar vasodilation which plays a major role in initiating the decrease in arterial blood volume. Therefore, administration of a vasoconstrictor may decrease paracentesis induced arteriolar vasodilation and prevent the resulting decrease in effective arterial blood volume. Two randomised pilot studies suggest that Terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. The combined treatment, albumin plus terlipressin, could have additional effect and may improve ascites in such patients. In several studies the combined therapy, albumin plus terlipressin, has shown beneficial effect in cirrhotic patients with hepatorenal syndrome characterized by a sever decrease in arterial blood volume and vasodilation. In these studies, combined therapy was well tolerated.The aim of this study is to compare ascites relapse between two groups of cirrhotic patients with recidivation ascites treated by paracentesis and intravenous albumin perfusion plus terlipressin or placebo. In this double blind randomized multi-center trial, all patients receive albumin perfusion at the dose 8 g/l of removed ascites and Terlipressin (1mg) or placebo, administrated before and at the end of the paracentesis.

Study Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Efficacy of Terlipressin in Cirrhotic Patients With Recidivation Ascites Treated With Paracentesis and Albumin. A Multi-center Randomized Controlled Study

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Terlipressin	Drug: Terlipressin Albumin perfusions at the dose 8 g/l of removed ascites and Terlipressin (1mg), administrated before and at the end of the paracentesis.
Placebo Comparator: Placebo	Drug: Placebo albumin perfusion at the dose 8 g/l of removed ascites and placebo, administrated before and at the end of the paracentesis.

Arm

Intervention/Treatment

Experimental: Terlipressin

Drug: Terlipressin

Albumin perfusions at the dose 8 g/l of removed ascites and Terlipressin (1mg), administrated before and at the end of the paracentesis.

Placebo Comparator: Placebo

Drug: Placebo

albumin perfusion at the dose 8 g/l of removed ascites and placebo, administrated before and at the end of the paracentesis.

Outcome Measures

Primary Outcome Measures

Mean number of paracentesis between the 2 groups over a 6 months period [6 months]

Secondary Outcome Measures

Total ascites retrieval [6 months]
Number of cirrhosis complications groups [6 months]
Liver transplantation and deaths [6 months]
Terlipressin safety [6 months]
Mean number of days of hospitalization [6 months]
Delay between inclusion and the first rehospitalisation for ascites retrieval [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient aged 18 years old and more with cirrhosis and refractory ascites define by the international ascites club.
Vital status non engaged in the 2 months

Exclusion Criteria:

cardiovascular disease : previous or actual angina pectoralis, myocardial infarction, heart failure, rhythm or conduction disorders, repolarisation abnormality on ECG
respiratory disease: previous or actual chronic pulmonary insufficiency, asthma
uncontrolled hypertension
acute portal vein thrombosis (less then 3 months) or currently treated.
chronic renal insufficiency (creatin > 15 mg/L)
severe hepatic encephalopathy
Alcoholic hepatitis or gastrointestinal bleeding in the last 3 months
hepatocellular carcinoma
severe illness with life threatening
pregnant or breastfeeding women