Human Albumin for the Treatment of Ascites in Patients With Hepatic Cirrhosis

Condition(s) targeted: Liver Cirrhosis; Ascites

Intervention: Diuretics plus human albumin (Drug); Diuretics (standard medical treatment) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: University of Bologna

Official(s) and/or principal investigator(s):
Mauro Bernardi, MD, Principal Investigator, Affiliation: University of Bologna, Italy
Paolo Caraceni, MD, Study Director, Affiliation: University of Bologna, Italy

Overall contact:
Paolo Caraceni, MD, Phone: 011390516362919, Email: paolo.caraceni@unibo.it

Ascites is the most frequent complication of liver cirrhosis and carries a significant worsening of the prognosis. Approximately 10% of patients per year develop refractory ascites because of either the lack of response to medical treatment or the onset of diuretic-induced complications that preclude the use of an effective dosage. Refractory ascites is associated with an increased incidence of severe complications of cirrhosis. Thus, the overall probability of survival of patients with refractory ascites is very poor, being approximately 30% at 2 years. Repeated large-volume paracentesis, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation represent the therapeutic alternatives for refractory ascites. As renal sodium retention and ascites formation are the consequence of portal hypertension and effective hypovolemia, the preservation of the central blood volume represents a major purpose in the management of patients with advanced cirrhosis. Although albumin is responsible for about 70% of the plasma oncotic pressure, the absence of large multicenter randomized studies together with its high cost explains why albumin infusion is not usually included among the therapeutic options for difficult-to-treat ascites.

The objective of the present study is to define the effectiveness of the prolonged administration of human albumin in the treatment of liver cirrhosis with ascitic decompensation. This goal will be reached by performing a multicenter, prospective, randomized clinical trial comparing the efficacy of chronic albumin administration on top of standard medical treatment versus standard medical treatment alone in patients with cirrhosis and ascites.

The study will be conducted in 44 Italian clinical centers and will enrol 440 in- or out-patients affected by liver cirrhosis with uncomplicated ascites who will be randomized with a ratio of 1: 1. The duration of the study for each patient is 18 months from randomization. The enrolment of patients will last 18 months and will be competitive between centers. Treatment will be interrupted if one of the following condition occur: orthotopic liver transplantation, TIPS, need of 3 paracentesis/month (indication to TIPS), patient refusal to continue, and medical judgement.

An ancillary optional study will be performed in a subset of patients to analyze the non-oncotic properties of albumin.

Official title: The Use of Human Albumin for the Treatment of Ascites in Patients With Hepatic Cirrhosis: a Multicenter, Open-label Randomized Clinical Trial

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mortality

Secondary outcome:

Incidence of cirrhosis-related clinical complications

Number of total paracentesis

Number of patients potentially needing TIPS (3 paracentesis/month)

Quality of life

Analysis of the cost/effectiveness ratio

Incidence of refractory ascites according to the IAC criteria

Detailed description: Background.

Ascites is the most frequent complication of liver cirrhosis and carries a significant worsening of the prognosis. Medical treatment of uncomplicated ascites is based on diuretics associated to a mild reduction of dietary sodium intake. Approximately 10% of patients per year develop refractory ascites, as defined by the International Ascites Club, because of either the lack of response to medical treatment or the onset of diuretic-induced complications that preclude the use of an effective dosage. Refractory ascites is associated with an increased incidence of severe complications of cirrhosis, such as hepatorenal syndromes (HRS), hyponatremia, spontaneous bacterial peritonitis (SBP), and umbilical hernia rupture and strangulation. Thus, the overall probability of survival of patients with refractory ascites is very poor, being approximately 30% at 2 years. Furthermore, the development of refractory ascites greatly deteriorates the patient's quality of life and substantially raises health costs, due to the frequent need for hospitalization and invasive procedures. Repeated large-volume paracentesis is the most widely accepted therapy for refractory ascites, although early recurrence of fluid accumulation occurs almost invariably. Transjugular intrahepatic portosystemic shunt (TIPS) is usually effective in preventing recurrence, but this procedure can be performed safely only in selected patients. Finally, refractory ascites represents an indication for liver transplantation in patients with no other contraindications.

Renal sodium retention and ascites formation are the consequence of portal hypertension and effective hypovolemia. The background of effective hypovolemia in advanced cirrhosis is represented by arteriolar vasodilation, which mainly occurs in the splanchnic circulatory area and evokes the compensatory activation of neuro-humoral systems able to promote vasoconstriction and renal retention of sodium and water.

Based on the above pathophysiological considerations, the preservation of the central blood volume represents a major purpose in the management of patients with advanced cirrhosis. Albumin constitutes approximately half of the proteins in the plasma of healthy individuals, and is responsible for about 70% of the plasma oncotic pressure. It plays, therefore, a pivotal role in modulating the distribution of fluid between compartments. However, albumin carries other biological properties, such as molecule and drug transport, free radical scavenging, and anti-inflammatory activity, which can be relevant under several circumstances and diseases. Finally, several controlled and/or randomized studies have shown that albumin administration is effective to prevent the circulatory dysfunction after large-volume paracentesis and renal failure after SBP, and to treat HRS when given together with vasoconstrictors. Furthermore, it is currently believed that its capacity to expand central blood volume in cirrhosis is superior to that of several plasma-expanders. In contrast, the chronic use of albumin to treat ascites is still debated, due to the lack of definitive scientific evidence supporting its clinical benefits. Thus, the absence of large multicenter randomized studies together with the high cost of the human albumin explains why albumin infusion is not usually included among the therapeutic options for difficult-to-treat ascites.

Objectives.

The objectives of the present study are to define the effectiveness of the prolonged administration of human albumin in the treatment of liver cirrhosis with ascitic decompensation. This goal will be reached by performing a multicenter, prospective, randomized clinical trial comparing the efficacy of chronic albumin administration on top of standard medical treatment versus standard medical treatment alone in patients with cirrhosis and ascites. The specific objectives of the present study are, therefore, to establish whether or not chronic albumin administration on top of standard medical treatment can improve patient outcomes.

Design of the Study.

The study will be conducted in 42 Italian clinical centers chosen for their high specialization in the management of patients with liver cirrhosis. The study population will consist of 440 in- or out-patients affected by liver cirrhosis with uncomplicated ascites. Patients with cirrhosis and uncomplicated ascites will randomized in two treatment groups:

- standard medical therapy (controls)

- standard medical therapy plus albumin infusion Within 24 hours from randomization,

patients will start with albumin infusion at the dose of 40 g twice weekly for 2 weeks, and then 40 g weekly for the rest of the study (up to 18 months). Patients who will develop refractory ascites during the study, will be followed up to completion of the 18 month period or to the need of at least 3 paracentesis/months. Human albumin, as 20%

solution - 50 ml, as they are available in the market, will by stored by the hospital

Pharmacies of participating Centers and will be given for the patients at the control visits.

Once eligibility to the study will be ascertained, centralized random allocation to the treatment groups will be achieved by means of a web-based service and will be accessible through Internet. Patients will be given an alpha-numeric identification code and randomized in a ratio of 1: 1 (standard medical treatment: standard medical treatment plus albumin). Randomization will be stratified according to the following conditions:

- Large volume paracentesis in the last month (yes; no)

- Hyponatremia, as reliable marker of renal function (< 135 mmol/L; ≥ 135 mmol/L)

Concomitant Therapies: patients with uncomplicated ascites will be treated with a mild hyposodic diet (approximately 100 mEq/die of Na+) and diuretics. According to the inclusion criteria, patients entering the study will be receiving at least 200 mg/die of an antimineralocorticoid drug and 25 mg/die of furosemide. Dose changes (increase/decrease) of the diuretic therapy will be permitted on the basis on the evolution of ascites decompensation. Total paracentesis can be performed in presence of tense ascites or symptoms due to the accumulation of abdominal fluid and will be followed by the administration of 8 g of albumin per liter of removed ascites. Patients who will develop refractory ascites during the study period will be treated with repeated total paracentesis. TIPS will be considered in patients presenting no other contraindications for this procedure when 3 or more therapeutic paracentesis per month will be needed. Complications such as SBP or HRS will be treated according to current indications, which include albumin infusion. There are any not allowed concomitant medication during the study.

Enrollment: the duration of the study for each patient is 18 months from randomization. The enrollment of patients will last 18 months and will be competitive between centers.

Visit Schedule: after the initial visit, patients will be evaluated every month.

Treatment interruption: each patient is fully entitled to stop his/her participation to the study, at any time. Moreover, patient participation to the study will be interrupted if it will be deemed beneficial to his/her health. Treatment will be interrupted if one of the following condition occur:

- Orthotopic liver transplantation

- TIPS

- Need of 3 paracentesis/month (indication to TIPS)

- Patient refusal to continue

- Medical judgment

Safety Evaluation: the evaluation of human albumin safety will consist in the monitoring and registration of adverse events, serious adverse events, laboratory tests, and vital signs. All events will be managed and reported in compliance with an applicable regulations, and included in the final clinical study report. Specific disease-related adverse events will be collected and documented as part of safety data but will be considered waived from expedited reporting to Regulatory Authorities. In this study, the following SAEs are considered related to the underlying condition and thus will not be considered unexpected unless their course, intensity or other specific features are such that the Investigator, according to his/her best medical judgment, considers these events as exceptional in the context of this medical condition:

- hepatic encephalopathy

- hepatocellular carcinoma

- gastrointestinal bleeding other than variceal bleeding

- bacterial peritonitis

- bacterial infections

- hepatorenal syndrome and renal failure with a non-fatal or fatal outcome

- non-fatal cholestasis

- deterioration of liver function (hyperbilirubinaemia, increased transaminases,

coagulopathy)

- serum electrolyte imbalance

- muscle cramps

Statistical Methods.

The study has been designed to demonstrate that the effect of prolonged albumin supplementation improves survival in patients with liver cirrhosis and uncomplicated ascites within 18 months from randomization.

The sample size calculations were based on the primary end-point defined above and calculated by using the Sample Power module included in SPSS11. 0, SPSS Inc, Chicago, USA.

- Hypothesis: 35% mortality (due to all causes) in the group of patients undergoing standard

medical care and 20% mortality in the group of patients receiving albumin (Wong at al, J Hepatol, 2011). In order to state that the difference in mortality between the two groups is statistically significant with 95% probability, 210 patients per arm have to be enrolled (power 90%). These figures have been calculated assuming a constant drop rate equal to 0. 04 per interval.

Ancillary Study.

An ancillary optional study will be performed in a subset of patients to analyze the non-oncotic properties of albumin. This is based on the recent novel observation that the binding, transport, and detoxification capacities of human albumin are severely compromised in patients with liver cirrhosis and this impairment correlates with the degree of liver failure.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion criteria

- Diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic and

ultrasonographic features) and uncomplicated ascites according to the criteria of the International Ascites Club (1).

- Ongoing diuretic treatment with an anti-mineralocorticoid drug at a dose of 200

mg/day and furosemide of 25 mg/day, stable for at least 4 days prior enrollment, not inducing response (defined according to the criteria of the International Ascites Club as body weight reduction ≥ 800 grams in the 4 days prior enrollment). 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).

- Ongoing diuretic treatment with an anti-mineralocorticoid drug at a dose > 200 mg/day

and furosemide > 25mg/day, independent of response to treatment.

- 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.

Exclusion criteria

- Age lower than 18 years

- No written informed consent

- Inability to follow written consent

- Established diagnosis of refractory ascites, as defined by the IAC (1)

- Need of 2 or more paracentesis during the last month

- Serum creatinine > 1. 5 mg/dl

- Organic nephropathy, as defined by the IAC (1)

- Hepatorenal syndrome type 1 in the last 15 days

- Gastrointestinal bleeding in the last 15 days

- Ongoing endoscopic eradication after a recent gastro-esophageal variceal bleeding

- Bacterial or fungal infection, including spontaneous bacterial peritonitis, in the

last 7 days

- Hepatic encephalopathy grade III/IV

- Budd-Chiari Syndrome

- Patients with TIPS or other surgical porto-caval shunts

- Known and suspected active hepatocellular carcinoma or other malignancies

- Previous liver transplantation

- Ongoing alcohol abuse (patients should be abstinent for at least three months)

- Antiviral therapy for hepatitis B started in the last 6 months

- Heart failure

- Respiratory failure as defined as PO2 <60 mmHg

- Known or suspected hypersensitivity to albumin

- Previous albumin administration given for the treatment of ascites in the last 30

days

- Patients enrolled in other clinical study for the treatment of ascites

- Use of experimental drugs for the last 2 months prior the inclusion in the present

study

- Pregnancy and breast-feeding

- 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

Paolo Caraceni, MD, Phone: 011390516362919, Email: paolo.caraceni@unibo.it

UO Gastroenterology, University of Ancona, Ancona, Italy; Recruiting
Antonio Benedetti, MD, Email: a.benedetti@ospedaliriuniti.marche.it
Gianluca Svegliati Baroni, MD, Email: g.svegliati@univpm.it
Antonio Benedetti, MD, Principal Investigator
Gianluca Svegliati Baroni, MD, Sub-Investigator
Samuele De Minicis, MD, Sub-Investigator

UO Gastroenterology, IRCCS De Bellis, Castellana Grotte-Bari, Bari, Italy; Recruiting
Raffaele Cozzolongo, Email: raffaelecln1@alice.it
Raffaele Cozzolongo, MD, Principal Investigator

UO Gastroenterology, University of Bari, Bari, Italy; Recruiting
Alfredo DI Leo, MD, Email: a.dileo@gastro.uniba.it
Maria Rendina, MD, Email: mariarendina@virgilio.it
Alfredo Di Leo, MD, Principal Investigator
Maria Rendina, MD, Sub-Investigator

UO Internal Medicine II, University of Cagliari, Cagliari, Italy; Recruiting
Luigi Demelia, MD, Email: ldemelia@pacs.unica.it
Alberto Civolani, MD, Email: alberto.civolani@virgilio.it
Luigi Demelia, MD, Principal Investigator
Alberto Civolani, MD, Sub-Investigator

UO Internal Medecine, University of Catania, Catania, Italy; Recruiting
Sergio Neri, MD, Email: sergio.neri4@tin.it
Daniela Maiorca, MD, Email: daniela.maiorca@hotmail.it
Sergio Neri, MD, Principal Investigator
Daniela Maiorca, MD, Sub-Investigator

UO Gastroenterology, University of Ferrara, Ferrara, Italy; Recruiting
Sergio Boccia, MD, Email: bcs@unife.it
Loredana Simone, MD, Email: loredana.simone@libero.it
Sergio Boccia, MD, Principal Investigator
Loredana Simone, MD, Sub-Investigator

UO Internal Medicine, AO University of Florence, Firenze, Italy; Recruiting
Giacomo Laffi, MD, Email: g.laffi@dfc.unifi.it
Giulio Romanelli, MD, Email: rgiulior@yahoo.it
Giacomo Laffi, MD, Principal Investigator
Giulio Romanelli, MD, Sub-Investigator

UO Gastroenterology, University of Foggia, Foggia, Italy; Recruiting
Carmine Panella, MD, Email: c.panella@unifg.it
Maurizio Nacchiero, MD, Email: mnacchiero@ospedaliriunitifoggia.it
Carmine Panella, MD, Principal Investigator
Maurizio Nacchiero, MD, Sub-Investigator

UO Internal Medicine, University of Messina, Messina, Italy; Recruiting
Giovanni Raimondo, MD, Email: raimondo@unime.it
Irene Cacciola, MD, Email: icacciola@unime.it
Giovanni Raimondo, MD, Principal Investigator
Irene Cacciola, MD, Sub-Investigator

UO Internal Medicine, Cotugno Hospital, Naples, Napoli, Italy; Recruiting
Vincenzo Sangiovanni, Email: esgv@libero.it
Vincenzo Sangiovanni, MD, Principal Investigator

UO Gastroenterology, University of Naples (AO University II), Napoli, Italy; Recruiting
Carmelina Loguercio, MD, Email: carmelina.loguercio@unina2.it
Alessandro Federico, MD, Email: alessandro.federico@unina2.it
Carmelina Loguercio, MD, Principal Investigator
Alessandro Federico, MD, Sub-Investigator

UO Gastroenterology, University of Naples (Federico II), Napoli, Italy; Recruiting
Nicola Caporaso, MD, Email: nicola.caporaso@unina.it
Filomena Morisco, MD, Email: filomena.morisco@unina.it
Nicola Caporaso, MD, Principal Investigator
Filomena Morisco, MD, Sub-Investigator

UO Gastroenterology, University of Palermo, Palermo, Italy; Recruiting
Vito Di Marco, MD, Email: vito.dimarco@tin.it
Vito Di Marco, MD, Principal Investigator

UO Gastroenterology, AO OORR Villa Sofia-Cervello of Palermo, Palermo, Italy; Recruiting
Gennaro D'Amico, Email: gedamico@libero.it
Gennaro D'Amico, MD, Principal Investigator

UO Gastroenterology, University of Pisa, Pisa, Italy; Recruiting
Santino Marchi, MD, Email: s.marchi@med.unipi.it
Angelo Ricchiuti, MD, Email: a.ricchiuti@int.med.unipi.it
Santino Marchi, MD, Principal Investigator
Angelo Ricchiuti, MD, Sub-Investigator

UO Internal Medicine, Hospital Of Rimini, Rimini, Italy; Recruiting
Giorgio Ballardini, MD, Email: giorgio.ballardini@auslrn.net
Natascia Celli, MD, Email: naticel@yahoo.it
Giorgio Ballardini, MD, Principal Investigator
Natascia Celli, MD, Sub-Investigator

UO Dept. of Internal Medicine, University of Rome, Policlinic Gemelli Of Rome, Roma, Italy; Recruiting
Antonio Gasbarrini, MD, Email: agasbarrini@rm.unicatt.it
Giovanni Gigante, MD, Email: vanny.gigante@libero.it
Antonio Gasbarrini, MD, Principal Investigator
Giovanni Gigante, MD, Sub-Investigator

UO Gastroenterology, University of Rome, Policlinic Sant'Andrea, Roma, Italy; Recruiting
Gianfranco Delle Fave, MD, Email: gianfranco.dellefave@uniroma1.it
Massimo Marignani, MD, Email: mmarignani@hotmail.com
Gianfranco Delle Fave, MD, Principal Investigator
Massimo Marignani, MD, Sub-Investigator
Paola Begini, MD, Sub-Investigator

UO Gastroenterology, Policlinic Tor Vergata, Rome, Roma, Italy; Recruiting
Mario Angelico, MD, Email: angelico@med.uniroma2.it
Cristiana Almerighi, MD, Email: cristiana.almerighi@uniroma2.it
Angelico Mario, MD, Principal Investigator
Cristiana Almerighi, MD, Sub-Investigator
Daniele Di Paolo, MD, Sub-Investigator

UO Gastroenterology, Policlinic Umberto I Rome, Rome, Italy; Recruiting
Oliviero Riggio, MD, Email: oliviero.riggio@uniroma1.it
Lorenzo Ridola, MD, Email: lorenzoridola@tiscali.it
Oliviero Riggio, MD, Principal Investigator
Lorenzo Ridola, MD, Sub-Investigator

UO Gastroenterology, Sacro Cuore Negrar Hospital, Verona, Verona, Italy; Recruiting
Maria Chiaramonte, MD, Email: maria.chiaramonte@sacrocuore.it
Maria Chiaramonte, MD, Principal Investigator

UO Gastroenterology, Riuniti Hospital Of Bergamo, Bergamo, BG, Italy; Recruiting
Stefano Fagiuoli, MD, Email: sfagiuoli@ospedaliriuniti.bergamo.it
Giulia Magini, MD, Email: giuliamag@hotmail.com
Stefano Fagiuoli, MD, Principal Investigator
Giulia Magini, MD, Sub-Investigator

UO Internal Medicine, Bentivoglio Hospital, Bologna, Bentivoglio, BO, Italy; Recruiting
Maurizio Ventrucci, Email: maurizio.ventrucci@ausl.bologna.it
Fabio Levantesi, MD, Email: f.levantesi@ausl.bo.it
Maurizio Ventrucci, MD, Principal Investigator
Fabio Levantesi, MD, Sub-Investigator

U.O. Semeiotica Medica, Dept. of Clinical Medicine, University of Bologna, Italy, Bologna, BO 40138, Italy; Recruiting
Paolo Caraceni, MD, Phone: 011390516362919, Email: paolo.caraceni@unibo.it
Federica Mirici, MD, Phone: 011390516362919, Email: federica.mirici@unibo.it
Mauro Bernardi, MD, Principal Investigator
Paolo Caraceni, MD, Sub-Investigator
Federica Mirici, MD, Sub-Investigator

UO Gastroenterology, General Hospital of Valduce, Como, Como, CO, Italy; Recruiting
Giancarlo Spinzi, MD, Email: gispinz@tin.it
Giancarlo Spinzi, Email: gispinz@tin.it
Giancarlo Spinzi, MD, Principal Investigator

UO Gastroenterology, Hospital of Cosenza, Cosenza, CS, Italy; Recruiting
Pietro Leo, MD, Email: pietro.leo@libero.it
Rosanna De Marco, MD, Email: rosanna.demarco1@tin.it
Pietro Leo, MD, Principal Investigator
Rosanna De Marco, MD, Sub-Investigator

Department of Internal Medicine, Bufalini Hospital of Cesena, Cesena, FC, Italy; Recruiting
Paolo Pazzi, MD, Email: ppazzi@ausl-cesena.emr.it
Paolo Pazzi, MD, Principal Investigator

UO Gastroenterology, AUSL 12 of Viareggio, Lucca, Lido di Camaiore, LU, Italy; Recruiting
Maurizio Lera, MD, Email: m.lera@usl12.toscana.it
Luigi Gatta, MD, Email: lgatta@mac.com
Maurizio Lera, MD, Principal Investigator
Luigi Gatta, MD, Sub-Investigator

UO Internal Medicine, IRCCS Policlinic S.Donato Milanese, Milan, Milano, MI, Italy; Recruiting
Francesco Salerno, MD, Email: francesco.salerno@unimi.it
Massimo Cazzaniga, MD
Francesco Salerno, MD, Principal Investigator
Massimo Cazzaniga, MD, Sub-Investigator

UO Hepatology and Gastroenterology, Ca' Granda-Niguarda Hospital of Milan, Milano, MI, Italy; Recruiting
Giovanbattista Pinzello, MD, Email: Giovanbattista.Pinzello@OspedaleNiguarda.it
Aldo Airoldi, MD, Email: Aldo.Airoldi@OspedaleNiguarda.it
Giovanbattista Pinzello, MD, Principal Investigator
Aldo Airoldi, MD, Sub-Investigator

UO Gastroenterology, Policlinic Mangiagalli and Regina-Elena of Milan, Milano, MI, Italy; Recruiting
Dario Conte, MD, Email: dario.conte@unimi.it
Sara Massironi, MD, Email: sara.massironi@libero.it
Dario Conte, MD, Principal Investigator
Sara Massironi, MD, Sub-Investigator

UO Gastroenterology, University of Modena, Italy, Modena, MO, Italy; Recruiting
Erica Villa, MD, Email: erica.villa@unimore.it
Maria Grazia Del Buono, MD, Email: mg.delbuono@gmail.com
Erica Villa, MD, Principal Investigator
Maria Grazia Del Buono, MD, Sub-Investigator
Anna Ferrari, MD, Sub-Investigator

UO Internal Medicine, University of Padova, Padova, PD, Italy; Recruiting
Paolo Angeli, MD, Email: pangeli@unipd.it
Paolo Angeli, MD, Principal Investigator

UO Department of infectious diseases and Hepatology, University of Parma, Parma, PR, Italy; Recruiting
Gianfranco Elia, MD, Email: gelia@ao.pr.it
Gianfranco Elia, MD, Principal Investigator

UO Internal Medicine, Faenza'S Hospital, Italy, Faenza, RA, Italy; Recruiting
Francesco Giuseppe Foschi, MD, Email: fg.foschi@ausl.ra.it
Francesco Giuseppe Foschi, MD, Principal Investigator

UO Internal Medicine, San Giuseppe Hospital-Marino, Marino, Roma, Italy; Recruiting
Claudio Puoti, MD, Email: puoti@epatologia.org
Riccardo Guarisco, MD, Email: riccardoguariscomd@msn.com
Claudio Puoti, MD, Principal Investigator
Riccardo Guarisco, MD, Sub-Investigator

UO Gastroenterology, Policlinic Gradenigo of Torino, Torino, TO, Italy; Recruiting
Floriano Rosina, MD, Email: floriano.rosina@h-gradenigo.it
Elisabetta Borghesio, MD, Email: elisabetta.borghesio@tiscali.it
Floriano Rosina, MD, Principal Investigator
Elisabetta Borghesio, MD, Sub-Investigator

UO Gastroenterology, University of Turine, Torino, TO, Italy; Recruiting
Mario Rizzetto, MD, Email: mrizzetto@molinette.piemonte.it
Carlo Alessandria, MD, Email: carloalessandria@libero.it
Mario Rizzetto, MD, Principal Investigator
Carlo Alessandria, MD, Sub-Investigator

UO Gastroenterology, Ca' Fondello Hospital, Treviso, Treviso, TV, Italy; Recruiting
Lajos Okolocsanji, MD, Email: lajos.okolicsanji@unipd.it
Marzia Groppo, MD, Email: mazgroppo@yahoo.com
Lajos Okolicsanji, MD, Principal Investigator
Marzia Groppo, MD, Sub-Investigator

UO Internal Medicine, University of Udine, Udine, UD, Italy; Recruiting
Pierluigi Toniutto, MD, Email: pierluigi.toniutto@uniud.it
Sara Bignulin, MD, Email: sara_bignulin@libero.it
Pierluigi Toniutto, MD, Principal Investigator
Sara Bignulin, MD, Sub-Investigator

UO Internal Medicine, Hospital of Dolo, Venice, Dolo, VE, Italy; Recruiting
Giuseppe Marin, MD, Email: giuseppe.marin@ulss13.mirano.ven.it
Giuseppe Marin, MD, Principal Investigator

UO Gastroenterology, AULSS 6 Of Vicenza, Vicenza, VI, Italy; Recruiting
Mario Salvagnini, MD, Email: mario.salvagnini@ulssvicenza.it
Mario Salvagnini, MD, Principal Investigator

Official site of the Italian Drug Agency

Related publications:

European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010 Sep;53(3):397-417. Epub 2010 Jun 1. Review. No abstract available.

Runyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107. No abstract available.

Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology. 2005 Jun;41(6):1211-9. Review. No abstract available.

Gentilini P, Casini-Raggi V, Di Fiore G, Romanelli RG, Buzzelli G, Pinzani M, La Villa G, Laffi G. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol. 1999 Apr;30(4):639-45.

Romanelli RG, La Villa G, Barletta G, Vizzutti F, Lanini F, Arena U, Boddi V, Tarquini R, Pantaleo P, Gentilini P, Laffi G. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. World J Gastroenterol. 2006 Mar 7;12(9):1403-7.

Starting date: March 2011
Last updated: December 11, 2011