Satavaptan Cirrhotic Ascites Treatment Study: a double-blind, randomised, parallel-group comparison of treatment with satavaptan at 5 to 10 mg daily versus placebo on top of conventional treatment in patients with ascites due to cirrhosis of the liver - CATS
- Conditions
- Cirrhotic ascitesMedDRA version: 8.1 Level: LLT Classification code 10003445
- Registration Number
- EUCTR2006-000132-27-GB
- Lead Sponsor
- Sanofi-aventis recherche & developpement
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 440
- 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 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 the case of more than one therapeutic 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
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 each).
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 >143 mmol/l
Serum potassium <3.5 mmol/l or >=5.0 mmol/l
Serum magnesium <0.65 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 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 c
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 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.;<br> 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:<br><br> Therapeutic paracentesis is defined as<br> - Removal of >=1 litres of ascitic fluid by paracentesis<br> OR<br> - 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)<br>
- Secondary Outcome Measures
Name Time Method