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

Phase 3
Completed
Conditions
Cirrhosis
Interventions
Drug: Placebo
Registration Number
NCT00986817
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
82
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
TerlipressinTerlipressin-
Primary Outcome Measures
NameTimeMethod
Mean number of paracentesis between the 2 groups over a 6 months period6 months
Secondary Outcome Measures
NameTimeMethod
Delay between inclusion and the first rehospitalisation for ascites retrieval6 months
Terlipressin safety6 months
Number of cirrhosis complications groups6 months
Mean number of days of hospitalization6 months
Total ascites retrieval6 months
Liver transplantation and deaths6 months

Trial Locations

Locations (1)

CARBONELL Nicolas

🇫🇷

Paris, France

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