E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ascites in patients with hepatic cirrhosis |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003445 |
E.1.2 | Term | Ascites |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objectives are: - increase in survival - improvement in the response to standard medical treatment and avoid/delay the occurrence of refractory ascites in patients with cirrhosis and uncomplicated ascites. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are: - to avoid/delay the need of transjugular intrahepatic porto-systemic shunt in patients with refractory ascites - reduction in the incidence of disease- and/or diuretic-related complications - improvement in the quality of life - reduction of the costs of patient management. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic and ultrasonographic features) and uncomplictaed ascites according to the criteria of the International Ascites Club (1). - Diuretic treatment, stable for at least 7 days prior the enrollemnt, with an antimineralocorticoid drug at a dose ≥ 200mg/day and furosemide ≥ 25mg/day. With this limitation, we aim to identify a fairly homogeneous population with a relatively advanced stage of the disease that will likely have more benefit from albumin administration, as also suggested by Gentilini at al. (17). - EGDS performed in the last 12 months, abdominal ultrasonography performed in the last 30 days, and laboratory tests required by the protocol in the last 7 days. |
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E.4 | Principal exclusion criteria |
- Age lower than 18 years - No written informed consent - Inability to follow written consent - Ongoing alcohol abuse (patients should be abstinent for at least three monts) - Established diagnosis of refractory ascites, as defined by the IAC (1) - Need of 3 or more paracentesis during the last two months - Serum creatinine > 1.6 mg/dl - Patients with TIPS or other surgical porto-caval shunts - Budd-Chiari Syndrome - Previous liver transplantation - Known hepatocellular carcinoma or other malignancies - Current / recent gastrointestinal bleeding, bacterial infection or type 1 hepatorenal syndrome - Renal failure due to intrinsic nephropathy - Patients with ascites of cardiac origin or due to peritoneal infection (e.g. tuberculosis) - Known or suspected hypersensitivity to albumin - Pregnancy and breast-feeding - Use of experimental drugs for the last 2 months prior the inclusion in the present study - Females of child-bearing potential are excluded unless they meet one of the following criteria: o Post-menopausal for 6 months or more, and if post-menopausal for less than 2 years, a negative pregnancy test o Surgical sterilisation for more than one month duration and a negative pregnancy test o Intrauterine device in combination with a secondary barrier (e.g. diaphragm, condom or spermicide) and a negative pregnancy test |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcomes. 1) reduction in the 24 month mortality; 2) reduction in the 24 month incidence of refractory ascites |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 36 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 8 |