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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2011 by University of Bologna.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Agenzia Italiana del Farmaco
Information provided by (Responsible Party):
Mauro Bernardi, University of Bologna
ClinicalTrials.gov Identifier:
NCT01288794
First received: February 1, 2011
Last updated: December 11, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Liver Cirrhosis
Ascites
Drug: Diuretics plus human albumin
Drug: Diuretics (standard medical treatment)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Use of Human Albumin for the Treatment of Ascites in Patients With Hepatic Cirrhosis: a Multicenter, Open-label Randomized Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of Bologna:

Primary Outcome Measures:
  • Mortality [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of cirrhosis-related clinical complications [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Number of total paracentesis [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Number of patients potentially needing TIPS (3 paracentesis/month) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    QoL will be assessed by the SF-36 and EQ-5D questionnaires

  • Analysis of the cost/effectiveness ratio [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Incidence of refractory ascites according to the IAC criteria [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 440
Study Start Date: March 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard medical treatment plus albumin
The patients will receive standard medical treatment (diuretics) plus weekly albumin infusion
Drug: Diuretics plus human albumin
The patients will receive standard medical treatment plus 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 24 months).
Other Names:
  • Furosemide and antialdosteronic drugs
  • Human albumin vials 50 cc 20% solution
Standard medical treatment
The patients will receive the standard medical treatment (diuretics), but non albumin for the therapy of ascites
Drug: Diuretics (standard medical treatment)
The patients will receive standard medical treatment (diuretics)
Other Name: Furosemide and antialdosteronic drugs

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01288794

Contacts
Contact: Paolo Caraceni, MD 011390516362919 paolo.caraceni@unibo.it
Contact: Federica Mirici, MD 011390516362919 federica.mirici@unibo.it

Locations
Italy
UO Gastroenterology, Riuniti Hospital Of Bergamo Recruiting
Bergamo, BG, Italy
Contact: Stefano Fagiuoli, MD       sfagiuoli@ospedaliriuniti.bergamo.it   
Contact: Giulia Magini, MD       giuliamag@hotmail.com   
Principal Investigator: Stefano Fagiuoli, MD         
Sub-Investigator: Giulia Magini, MD         
UO Internal Medicine, Bentivoglio Hospital, Bologna Recruiting
Bentivoglio, BO, Italy
Contact: Maurizio Ventrucci       maurizio.ventrucci@ausl.bologna.it   
Contact: Fabio Levantesi, MD       f.levantesi@ausl.bo.it   
Principal Investigator: Maurizio Ventrucci, MD         
Sub-Investigator: Fabio Levantesi, MD         
U.O. Semeiotica Medica, Dept. of Clinical Medicine, University of Bologna, Italy Recruiting
Bologna, BO, Italy, 40138
Contact: Paolo Caraceni, MD    011390516362919    paolo.caraceni@unibo.it   
Contact: Federica Mirici, MD    011390516362919    federica.mirici@unibo.it   
Principal Investigator: Mauro Bernardi, MD         
Sub-Investigator: Paolo Caraceni, MD         
Sub-Investigator: Federica Mirici, MD         
UO Gastroenterology, General Hospital of Valduce, Como Recruiting
Como, CO, Italy
Contact: Giancarlo Spinzi, MD       gispinz@tin.it   
Contact: Giancarlo Spinzi       gispinz@tin.it   
Principal Investigator: Giancarlo Spinzi, MD         
UO Gastroenterology, Hospital of Cosenza Recruiting
Cosenza, CS, Italy
Contact: Pietro Leo, MD       pietro.leo@libero.it   
Contact: Rosanna De Marco, MD       rosanna.demarco1@tin.it   
Principal Investigator: Pietro Leo, MD         
Sub-Investigator: Rosanna De Marco, MD         
Department of Internal Medicine, Bufalini Hospital of Cesena Recruiting
Cesena, FC, Italy
Contact: Paolo Pazzi, MD       ppazzi@ausl-cesena.emr.it   
Principal Investigator: Paolo Pazzi, MD         
UO Gastroenterology, AUSL 12 of Viareggio, Lucca Recruiting
Lido di Camaiore, LU, Italy
Contact: Maurizio Lera, MD       m.lera@usl12.toscana.it   
Contact: Luigi Gatta, MD       lgatta@mac.com   
Principal Investigator: Maurizio Lera, MD         
Sub-Investigator: Luigi Gatta, MD         
UO Internal Medicine, IRCCS Policlinic S.Donato Milanese, Milan Recruiting
Milano, MI, Italy
Contact: Francesco Salerno, MD       francesco.salerno@unimi.it   
Contact: Massimo Cazzaniga, MD         
Principal Investigator: Francesco Salerno, MD         
Sub-Investigator: Massimo Cazzaniga, MD         
UO Hepatology and Gastroenterology, Ca' Granda-Niguarda Hospital of Milan Recruiting
Milano, MI, Italy
Contact: Giovanbattista Pinzello, MD       Giovanbattista.Pinzello@OspedaleNiguarda.it   
Contact: Aldo Airoldi, MD       Aldo.Airoldi@OspedaleNiguarda.it   
Principal Investigator: Giovanbattista Pinzello, MD         
Sub-Investigator: Aldo Airoldi, MD         
UO Gastroenterology, Policlinic Mangiagalli and Regina-Elena of Milan Recruiting
Milano, MI, Italy
Contact: Dario Conte, MD       dario.conte@unimi.it   
Contact: Sara Massironi, MD       sara.massironi@libero.it   
Principal Investigator: Dario Conte, MD         
Sub-Investigator: Sara Massironi, MD         
UO Gastroenterology, University of Modena, Italy Recruiting
Modena, MO, Italy
Contact: Erica Villa, MD       erica.villa@unimore.it   
Contact: Maria Grazia Del Buono, MD       mg.delbuono@gmail.com   
Principal Investigator: Erica Villa, MD         
Sub-Investigator: Maria Grazia Del Buono, MD         
Sub-Investigator: Anna Ferrari, MD         
UO Internal Medicine, University of Padova Recruiting
Padova, PD, Italy
Contact: Paolo Angeli, MD       pangeli@unipd.it   
Principal Investigator: Paolo Angeli, MD         
UO Department of infectious diseases and Hepatology, University of Parma Recruiting
Parma, PR, Italy
Contact: Gianfranco Elia, MD       gelia@ao.pr.it   
Principal Investigator: Gianfranco Elia, MD         
UO Internal Medicine, Faenza'S Hospital, Italy Recruiting
Faenza, RA, Italy
Contact: Francesco Giuseppe Foschi, MD       fg.foschi@ausl.ra.it   
Principal Investigator: Francesco Giuseppe Foschi, MD         
UO Internal Medicine, San Giuseppe Hospital-Marino Recruiting
Marino, Roma, Italy
Contact: Claudio Puoti, MD       puoti@epatologia.org   
Contact: Riccardo Guarisco, MD       riccardoguariscomd@msn.com   
Principal Investigator: Claudio Puoti, MD         
Sub-Investigator: Riccardo Guarisco, MD         
UO Gastroenterology, Policlinic Gradenigo of Torino Recruiting
Torino, TO, Italy
Contact: Floriano Rosina, MD       floriano.rosina@h-gradenigo.it   
Contact: Elisabetta Borghesio, MD       elisabetta.borghesio@tiscali.it   
Principal Investigator: Floriano Rosina, MD         
Sub-Investigator: Elisabetta Borghesio, MD         
UO Gastroenterology, University of Turine Recruiting
Torino, TO, Italy
Contact: Mario Rizzetto, MD       mrizzetto@molinette.piemonte.it   
Contact: Carlo Alessandria, MD       carloalessandria@libero.it   
Principal Investigator: Mario Rizzetto, MD         
Sub-Investigator: Carlo Alessandria, MD         
UO Gastroenterology, Ca' Fondello Hospital, Treviso Recruiting
Treviso, TV, Italy
Contact: Lajos Okolocsanji, MD       lajos.okolicsanji@unipd.it   
Contact: Marzia Groppo, MD       mazgroppo@yahoo.com   
Principal Investigator: Lajos Okolicsanji, MD         
Sub-Investigator: Marzia Groppo, MD         
UO Internal Medicine, University of Udine Recruiting
Udine, UD, Italy
Contact: Pierluigi Toniutto, MD       pierluigi.toniutto@uniud.it   
Contact: Sara Bignulin, MD       sara_bignulin@libero.it   
Principal Investigator: Pierluigi Toniutto, MD         
Sub-Investigator: Sara Bignulin, MD         
UO Internal Medicine, Hospital of Dolo, Venice Recruiting
Dolo, VE, Italy
Contact: Giuseppe Marin, MD       giuseppe.marin@ulss13.mirano.ven.it   
Principal Investigator: Giuseppe Marin, MD         
UO Gastroenterology, AULSS 6 Of Vicenza Recruiting
Vicenza, VI, Italy
Contact: Mario Salvagnini, MD       mario.salvagnini@ulssvicenza.it   
Principal Investigator: Mario Salvagnini, MD         
UO Gastroenterology, University of Ancona Recruiting
Ancona, Italy
Contact: Antonio Benedetti, MD       a.benedetti@ospedaliriuniti.marche.it   
Contact: Gianluca Svegliati Baroni, MD       g.svegliati@univpm.it   
Principal Investigator: Antonio Benedetti, MD         
Sub-Investigator: Gianluca Svegliati Baroni, MD         
Sub-Investigator: Samuele De Minicis, MD         
UO Gastroenterology, IRCCS De Bellis, Castellana Grotte-Bari Recruiting
Bari, Italy
Contact: Raffaele Cozzolongo       raffaelecln1@alice.it   
Principal Investigator: Raffaele Cozzolongo, MD         
UO Gastroenterology, University of Bari Recruiting
Bari, Italy
Contact: Alfredo DI Leo, MD       a.dileo@gastro.uniba.it   
Contact: Maria Rendina, MD       mariarendina@virgilio.it   
Principal Investigator: Alfredo Di Leo, MD         
Sub-Investigator: Maria Rendina, MD         
UO Internal Medicine II, University of Cagliari Recruiting
Cagliari, Italy
Contact: Luigi Demelia, MD       ldemelia@pacs.unica.it   
Contact: Alberto Civolani, MD       alberto.civolani@virgilio.it   
Principal Investigator: Luigi Demelia, MD         
Sub-Investigator: Alberto Civolani, MD         
UO Internal Medecine, University of Catania Recruiting
Catania, Italy
Contact: Sergio Neri, MD       sergio.neri4@tin.it   
Contact: Daniela Maiorca, MD       daniela.maiorca@hotmail.it   
Principal Investigator: Sergio Neri, MD         
Sub-Investigator: Daniela Maiorca, MD         
UO Gastroenterology, University of Ferrara Recruiting
Ferrara, Italy
Contact: Sergio Boccia, MD       bcs@unife.it   
Contact: Loredana Simone, MD       loredana.simone@libero.it   
Principal Investigator: Sergio Boccia, MD         
Sub-Investigator: Loredana Simone, MD         
UO Internal Medicine, AO University of Florence Recruiting
Firenze, Italy
Contact: Giacomo Laffi, MD       g.laffi@dfc.unifi.it   
Contact: Giulio Romanelli, MD       rgiulior@yahoo.it   
Principal Investigator: Giacomo Laffi, MD         
Sub-Investigator: Giulio Romanelli, MD         
UO Gastroenterology, University of Foggia Recruiting
Foggia, Italy
Contact: Carmine Panella, MD       c.panella@unifg.it   
Contact: Maurizio Nacchiero, MD       mnacchiero@ospedaliriunitifoggia.it   
Principal Investigator: Carmine Panella, MD         
Sub-Investigator: Maurizio Nacchiero, MD         
UO Internal Medicine, University of Messina Recruiting
Messina, Italy
Contact: Giovanni Raimondo, MD       raimondo@unime.it   
Contact: Irene Cacciola, MD       icacciola@unime.it   
Principal Investigator: Giovanni Raimondo, MD         
Sub-Investigator: Irene Cacciola, MD         
UO Internal Medicine, Cotugno Hospital, Naples Recruiting
Napoli, Italy
Contact: Vincenzo Sangiovanni       esgv@libero.it   
Principal Investigator: Vincenzo Sangiovanni, MD         
UO Gastroenterology, University of Naples (AO University II) Recruiting
Napoli, Italy
Contact: Carmelina Loguercio, MD       carmelina.loguercio@unina2.it   
Contact: Alessandro Federico, MD       alessandro.federico@unina2.it   
Principal Investigator: Carmelina Loguercio, MD         
Sub-Investigator: Alessandro Federico, MD         
UO Gastroenterology, University of Naples (Federico II) Recruiting
Napoli, Italy
Contact: Nicola Caporaso, MD       nicola.caporaso@unina.it   
Contact: Filomena Morisco, MD       filomena.morisco@unina.it   
Principal Investigator: Nicola Caporaso, MD         
Sub-Investigator: Filomena Morisco, MD         
UO Gastroenterology, University of Palermo Recruiting
Palermo, Italy
Contact: Vito Di Marco, MD       vito.dimarco@tin.it   
Principal Investigator: Vito Di Marco, MD         
UO Gastroenterology, AO OORR Villa Sofia-Cervello of Palermo Recruiting
Palermo, Italy
Contact: Gennaro D'Amico       gedamico@libero.it   
Principal Investigator: Gennaro D'Amico, MD         
UO Gastroenterology, University of Pisa Recruiting
Pisa, Italy
Contact: Santino Marchi, MD       s.marchi@med.unipi.it   
Contact: Angelo Ricchiuti, MD       a.ricchiuti@int.med.unipi.it   
Principal Investigator: Santino Marchi, MD         
Sub-Investigator: Angelo Ricchiuti, MD         
UO Internal Medicine, Hospital Of Rimini Recruiting
Rimini, Italy
Contact: Giorgio Ballardini, MD       giorgio.ballardini@auslrn.net   
Contact: Natascia Celli, MD       naticel@yahoo.it   
Principal Investigator: Giorgio Ballardini, MD         
Sub-Investigator: Natascia Celli, MD         
UO Dept. of Internal Medicine, University of Rome, Policlinic Gemelli Of Rome Recruiting
Roma, Italy
Contact: Antonio Gasbarrini, MD       agasbarrini@rm.unicatt.it   
Contact: Giovanni Gigante, MD       vanny.gigante@libero.it   
Principal Investigator: Antonio Gasbarrini, MD         
Sub-Investigator: Giovanni Gigante, MD         
UO Gastroenterology, University of Rome, Policlinic Sant'Andrea Recruiting
Roma, Italy
Contact: Gianfranco Delle Fave, MD       gianfranco.dellefave@uniroma1.it   
Contact: Massimo Marignani, MD       mmarignani@hotmail.com   
Principal Investigator: Gianfranco Delle Fave, MD         
Sub-Investigator: Massimo Marignani, MD         
Sub-Investigator: Paola Begini, MD         
UO Gastroenterology, Policlinic Tor Vergata, Rome Recruiting
Roma, Italy
Contact: Mario Angelico, MD       angelico@med.uniroma2.it   
Contact: Cristiana Almerighi, MD       cristiana.almerighi@uniroma2.it   
Principal Investigator: Angelico Mario, MD         
Sub-Investigator: Cristiana Almerighi, MD         
Sub-Investigator: Daniele Di Paolo, MD         
UO Gastroenterology, Policlinic Umberto I Rome Recruiting
Rome, Italy
Contact: Oliviero Riggio, MD       oliviero.riggio@uniroma1.it   
Contact: Lorenzo Ridola, MD       lorenzoridola@tiscali.it   
Principal Investigator: Oliviero Riggio, MD         
Sub-Investigator: Lorenzo Ridola, MD         
UO Gastroenterology, Sacro Cuore Negrar Hospital, Verona Recruiting
Verona, Italy
Contact: Maria Chiaramonte, MD       maria.chiaramonte@sacrocuore.it   
Principal Investigator: Maria Chiaramonte, MD         
Sponsors and Collaborators
University of Bologna
Agenzia Italiana del Farmaco
Investigators
Principal Investigator: Mauro Bernardi, MD University of Bologna, Italy
Study Director: Paolo Caraceni, MD University of Bologna, Italy
  More Information

Additional Information:
Publications:
Responsible Party: Mauro Bernardi, Full Professor of Medicine, University of Bologna
ClinicalTrials.gov Identifier: NCT01288794     History of Changes
Other Study ID Numbers: FARM6P824B, 2008-000625-19
Study First Received: February 1, 2011
Last Updated: December 11, 2011
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by University of Bologna:
Cirrhosis
Uncomplicated ascites
Refractory ascites
Chronic albumin treatment

Additional relevant MeSH terms:
Ascites
Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Diuretics
Furosemide
Albunex
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Therapeutic Uses
Contrast Media
Diagnostic Uses of Chemicals

ClinicalTrials.gov processed this record on September 14, 2014