Cirrhotic ascites MedDRA version: 8.1 Level: LLT Classification code 10003445
Conditions
Sponsors
sanofi-aventis R&D
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with cirrhosis of the liver confirmed by histology and/or a combination of either ultrasound, CT or endoscopic examination with laboratory evidence (e.g. low platelet count, low serum albumin, elevated total serum bilirubin or elevated INR). - Patients with clinically evident ascites primarily managed by diet and/or diuretics Patients should have a physical exam compatible with diagnosis of ascites (e.g. abdominal distension with confirmation of ascites by presence of at least one of the following signs: fluid wave, shifting dullness, bulging flanks lying supine, tympany at the top of the abdominal curve while supine, or presence of Puddle sign) or confirmation of ascites by ultrasound or by diagnostic paracentesis - Stable treatment of ascites for at least the previous 2 weeks without paracentesis Patients may have undergone either no therapeutic paracentesis, or only one therapeutic paracentesis, or in case of more than one therapetic paracentesis in the previous 6 months, the interval between the last 2 paracentesis must be > 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
Exclusion criteria: 1) Related to study methodology Age 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 143 mmol/l Serum potassium 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 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 E: - Aprepitant, atazanavir, chloramphenicol, clarithromycin, cremophor EL, cyclosporine, 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of satavaptan on top of conventional treatment in the treatment of clinically evident ascites in patients with cirrhosis of the liver.;Secondary Objective: To evaluate the tolerability and safety of satavaptan over a 52-week treatment period in patients with cirrhosis of the liver and ascites.;Primary end point(s): The primary endpoint is the proportion of patients with ascites worsening at 12 weeks. This endpoint will be defined by any of the following criteria occurring during the first 12 weeks of the study: Therapeutic paracentesis is defined as - Removal of >=1 litres of ascitic fluid by paracentesis OR - Weight increase of >=2 kg since the baseline measurement on Day 1 before the first intake of study medication (including the weight of any ascitic fluid removed by paracentesis) | — |
Countries
Belgium, Denmark, Hungary, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom
Outcome results
None listed