Satavaptan in the Prevention of Ascites Recurrence: a double-blind, randomised, parallel-group comparison of satavaptan at 5 to 10 mg daily versus placebo with concomitant diuretics in patients with recurrent ascites due to cirrhosis of the liver - SPARe-1

• Conditions: Cirrhotic ascites; MedDRA version: 8.1Level: LLTClassification code 10003445

• Registration Number: EUCTR2006-000134-12-GB
• Lead Sponsor: Sanofi-Synthelabo Recherche

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-04-03
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

- Patients with cirrhosis of the liver confirmed by histology and/or a combination of either ultrasound or endoscopic examination with laboratory evidence (e.g. low platelet count, low serum albumin, elevated total serum bilirubin or elevated INR).
- Patients with recurrent ascites having undergone both of the following:
. therapeutic paracentesis for the removal of ascites in the previous 24 hours with the removal of >= 4 litres of fluid,
. at least one other therapeutic paracentesis in the previous 3 months.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Related to study methodology
Age <18 years
No written informed consent
Inability to follow verbal and written instructions.
Patients with an existing functional TIPS (transjugular intrahepatic portosystemic shunt) or other shunt designed to transfer blood from the portal system to the systemic circulation bypassing the liver.
Budd-Chiari syndrome
Patients with positive HBV DNA who have started antiviral treatment in the previous 4 weeks or in whom such treatment is planned to start during the next 12 weeks.
Previous liver transplantation
Known hepatocellular carcinoma (unless only one lesion <5 cm diameter or no more than 3 nodules of <3 cm).
Sepsis or spontaneous bacterial peritonitis currently or in the 10 days before randomisation.
Current hepatic encephalopathy (>grade 1 by the West Haven criteria, Appendix B) evaluated by clinical features
Known gastrointestinal bleeding currently or in the 10 days before randomisation.
QTcF interval on an ECG >= 480 ms.
Patients with ascites of cardiac origin or due to peritoneal infection (e.g. tuberculosis) or peritoneal carcinoma
Serum bilirubin >150 µmol/l
INR >3.0, neutrophils <1 000/mm3, platelets <30 000/mm3.
Patients previously exposed to satavaptan in the past 12 months

2) Related to satavaptan
Haemodynamic insufficiency (systolic arterial pressure <80 mmHg or symptomatic orthostatic hypotension)
Serum sodium >142 mmol/l
Serum potassium >= 5.0 mmol/l
Significant renal impairment with serum creatinine >150 µmol/l
Positive pregnancy test
Females of child-bearing potential are excluded unless they meet one of the following criteria:
. Post-menopausal for 6 months or more, and if post-menopausal for less than 2 years, a negative pregnancy test
. Surgical sterilisation for more than one month duration and a negative pregnancy test
. Intrauterine device in combination with a secondary barrier (e.g. diaphragm, condom or spermicide) and a negative pregnancy test
. Oral contraceptive in combination with a secondary barrier (e.g. diaphragm, condom or spermicide) and a negative pregnancy test.
. Known hypersensitivity to satavaptan
Administration of inducers of CYP3A listed below within the two weeks prior to study drug administration:
. carbamazepine, phenobarbital, phenytoin, rifampicin (rifampin), Saint John's Wort
· Administration of potent and selected moderate inhibitors of CYP3A, which may significantly increase exposure to the study drug within the two weeks prior to study drug administration. These are listed below and in Appendix F:
. Aprepitant, atazanavir, chloramphenicol, clarithromycin, cremophor EL, cyclosporin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, verapamil
Patients taking other drugs known to increase the risk of hyperkalaemia in addition to spironolactone, potassium canrenoate or eplerenone may not be included in the study in order to avoid an additive effect on serum potassium concentrations (e.g. angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of satavaptan on top of diuretic drugs in reducing the recurrence of ascites.;Secondary Objective: To evaluate the tolerability and safety of satavaptan on top of diuretic drugs over a 52-week treatment period in patients with cirrhosis of the liver and recurrent ascites.;Primary end point(s): The primary endpoint is the number and time (from randomisation) of recurrences of therapeutic paracenteses occurring during the first 12 weeks of the double blind period of the study. Therapeutic paracentesis will be defined as the removal of >= 2 litres of ascitic fluid by paracentesis.