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

This study is currently recruiting participants.
Verified March 2014 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00986817
First received: September 29, 2009
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Cirrhosis
Drug: Terlipressin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Mean number of paracentesis between the 2 groups over a 6 months period [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total ascites retrieval [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Number of cirrhosis complications groups [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Liver transplantation and deaths [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Terlipressin safety [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Mean number of days of hospitalization [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Delay between inclusion and the first rehospitalisation for ascites retrieval [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: November 2009
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other Name: Terlipressin
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.
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00986817

Contacts
Contact: Nicolas CARBONELL, MD 01 49 28 23 78 nicolas.carbonell@sat.aphp.fr

Locations
France
CARBONELL Nicolas Recruiting
Paris, France, 75012
Contact: Nicolas Carbonell, MD    01 49 28 23 78    nicolas.carbonell@sat.aphp.fr   
Principal Investigator: Nicolas Carbonell, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Nicolas Carbonell, MD Hôpital Saint Antoine
  More Information

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00986817     History of Changes
Other Study ID Numbers: P071215
Study First Received: September 29, 2009
Last Updated: March 4, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Refractory ascites
Cirrhosis Terlipressin
Paracentesis

Additional relevant MeSH terms:
Ascites
Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Terlipressin
Lypressin
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs
Hemostatics
Coagulants
Hematologic Agents

ClinicalTrials.gov processed this record on April 17, 2014