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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University of Bologna
Agenzia Italiana del Farmaco
Information provided by (Responsible Party):
Mauro Bernardi, University of Bologna Identifier:
First received: February 1, 2011
Last updated: October 23, 2014
Last verified: October 2014

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
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: May 2016
Estimated Primary Completion Date: November 2014 (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


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 identifier: NCT01288794

Contact: Paolo Caraceni, MD 011390516362919
Contact: Federica Mirici, MD 011390516362919

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Sub-Investigator: Giulia Magini, MD         
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U.O. Semeiotica Medica, Dept. of Clinical Medicine, University of Bologna, Italy Recruiting
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Contact: Paolo Pazzi, MD   
Principal Investigator: Paolo Pazzi, MD         
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Contact: Dario Conte, MD   
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Sub-Investigator: Sara Massironi, MD         
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Contact: Francesco Salerno, MD   
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Sub-Investigator: Aldo Airoldi, MD         
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Sub-Investigator: Anna Ferrari, MD         
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Contact: Paolo Angeli, MD   
Principal Investigator: Paolo Angeli, MD         
UO Department of infectious diseases and Hepatology, University of Parma Recruiting
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Contact: Gianfranco Elia, MD   
Principal Investigator: Gianfranco Elia, MD         
UO Internal Medicine, Faenza'S Hospital, Italy Recruiting
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Contact: Francesco Giuseppe Foschi, MD   
Principal Investigator: Francesco Giuseppe Foschi, MD         
UO Internal Medicine, San Giuseppe Hospital-Marino Recruiting
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Contact: Claudio Puoti, MD   
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Principal Investigator: Claudio Puoti, MD         
Sub-Investigator: Riccardo Guarisco, MD         
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Contact: Mario Rizzetto, MD   
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Principal Investigator: Mario Rizzetto, MD         
Sub-Investigator: Carlo Alessandria, MD         
UO Internal Medicine, University of Udine Recruiting
Udine, UD, Italy
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Principal Investigator: Pierluigi Toniutto, MD         
Sub-Investigator: Sara Bignulin, MD         
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UO Gastroenterology, University of Ancona Recruiting
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Sub-Investigator: Maria Rendina, MD         
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Sub-Investigator: Daniela Maiorca, MD         
UO Gastroenterology, University of Ferrara Recruiting
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UO Internal Medicine, AO University of Florence Recruiting
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UO Internal Medicine, University of Messina Recruiting
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Contact: Giovanni Raimondo, MD   
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Sub-Investigator: Irene Cacciola, MD         
UO Internal Medicine, Cotugno Hospital, Naples Recruiting
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Contact: Vincenzo Sangiovanni   
Principal Investigator: Vincenzo Sangiovanni, MD         
UO Gastroenterology, University of Naples (Federico II) Recruiting
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Contact: Nicola Caporaso, MD   
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Principal Investigator: Nicola Caporaso, MD         
Sub-Investigator: Filomena Morisco, MD         
UO Gastroenterology, University of Naples (AO University II) Recruiting
Napoli, Italy
Contact: Carmelina Loguercio, MD   
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Principal Investigator: Carmelina Loguercio, MD         
Sub-Investigator: Alessandro Federico, MD         
UO Gastroenterology, University of Palermo Recruiting
Palermo, Italy
Contact: Vito Di Marco, MD   
Principal Investigator: Vito Di Marco, MD         
UO Internal Medicine, Hospital Of Rimini Recruiting
Rimini, Italy
Contact: Giorgio Ballardini, MD   
Contact: Natascia Celli, MD   
Principal Investigator: Giorgio Ballardini, MD         
Sub-Investigator: Natascia Celli, MD         
UO Gastroenterology, University of Rome, Policlinic Sant'Andrea Recruiting
Roma, Italy
Contact: Gianfranco Delle Fave, MD   
Contact: Massimo Marignani, MD   
Principal Investigator: Gianfranco Delle Fave, MD         
Sub-Investigator: Massimo Marignani, MD         
Sub-Investigator: Paola Begini, MD         
UO Gastroenterology, Policlinic Tor Vergata, Rome Recruiting
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Contact: Mario Angelico, MD   
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Principal Investigator: Angelico Mario, MD         
Sub-Investigator: Cristiana Almerighi, MD         
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Sponsors and Collaborators
University of Bologna
Agenzia Italiana del Farmaco
Principal Investigator: Mauro Bernardi, MD University of Bologna, Italy
Study Director: Paolo Caraceni, MD University of Bologna, Italy
  More Information

Additional Information:
Responsible Party: Mauro Bernardi, Full Professor of Medicine, University of Bologna Identifier: NCT01288794     History of Changes
Other Study ID Numbers: FARM6P824B, 2008-000625-19
Study First Received: February 1, 2011
Last Updated: October 23, 2014
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

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

Additional relevant MeSH terms:
Liver Cirrhosis
Digestive System Diseases
Liver Diseases
Pathologic Processes
Cardiovascular Agents
Contrast Media
Diagnostic Uses of Chemicals
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Therapeutic Uses processed this record on October 29, 2014