Human Albumin for the Treatment of Ascites in Patients With Hepatic Cirrhosis
ANSWER
The Use of Human Albumin for the Treatment of Ascites in Patients With Hepatic Cirrhosis: a Multicenter, Open-label Randomized Clinical Trial
2 other identifiers
interventional
431
1 country
33
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Mar 2011
Longer than P75 for phase_4
33 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2011
CompletedFirst Posted
Study publicly available on registry
February 2, 2011
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2016
CompletedJanuary 20, 2017
January 1, 2017
3.7 years
February 1, 2011
January 19, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Mortality
18 months
Secondary Outcomes (6)
Incidence of cirrhosis-related clinical complications
18 months
Number of total paracentesis
18 months
Number of patients potentially needing TIPS (3 paracentesis/month)
18 months
Quality of life
18 months
Analysis of the cost/effectiveness ratio
18 months
- +1 more secondary outcomes
Study Arms (2)
Standard medical treatment plus albumin
ACTIVE COMPARATORThe patients will receive standard medical treatment (diuretics) plus weekly albumin infusion
Standard medical treatment
OTHERThe patients will receive the standard medical treatment (diuretics), but non albumin for the therapy of ascites
Interventions
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).
The patients will receive standard medical treatment (diuretics)
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Bolognalead
- Agenzia Italiana del Farmacocollaborator
Study Sites (33)
UO Gastroenterology, Riuniti Hospital Of Bergamo
Bergamo, BG, Italy
UO Internal Medicine, Bentivoglio Hospital, Bologna
Bentivoglio, BO, Italy
U.O. Semeiotica Medica, Dept. of Clinical Medicine, University of Bologna, Italy
Bologna, BO, 40138, Italy
UO Gastroenterology, General Hospital of Valduce, Como
Como, CO, Italy
UO Gastroenterology, Hospital of Cosenza
Cosenza, CS, Italy
Department of Internal Medicine, Bufalini Hospital of Cesena
Cesena, FC, Italy
UO Gastroenterology, Policlinic Mangiagalli and Regina-Elena of Milan
Milan, MI, Italy
UO Hepatology and Gastroenterology, Ca' Granda-Niguarda Hospital of Milan
Milan, MI, Italy
UO Internal Medicine, IRCCS Policlinic S.Donato Milanese, Milan
Milan, MI, Italy
UO Gastroenterology, University of Modena, Italy
Modena, MO, Italy
UO Internal Medicine, University of Padova
Padua, PD, Italy
UO Department of infectious diseases and Hepatology, University of Parma
Parma, PR, Italy
UO Internal Medicine, Faenza'S Hospital, Italy
Faenza, RA, Italy
UO Internal Medicine, San Giuseppe Hospital-Marino
Marino, Roma, Italy
UO Gastroenterology, University of Turine
Torino, TO, Italy
UO Internal Medicine, University of Udine
Udine, UD, Italy
UO Internal Medicine, Hospital of Dolo, Venice
Dolo, VE, Italy
UO Gastroenterology, University of Ancona
Ancona, Italy
UO Gastroenterology, IRCCS De Bellis, Castellana Grotte-Bari
Bari, Italy
UO Gastroenterology, University of Bari
Bari, Italy
UO Internal Medecine, University of Catania
Catania, Italy
UO Gastroenterology, University of Ferrara
Ferrara, Italy
UO Internal Medicine, AO University of Florence
Florence, Italy
UO Internal Medicine, University of Messina
Messina, Italy
UO Gastroenterology, University of Naples (AO University II)
Napoli, Italy
UO Gastroenterology, University of Naples (Federico II)
Napoli, Italy
UO Internal Medicine, Cotugno Hospital, Naples
Napoli, Italy
UO Gastroenterology, University of Palermo
Palermo, Italy
UO Internal Medicine, Hospital Of Rimini
Rimini, Italy
UO Dept. of Internal Medicine, University of Rome, Policlinic Gemelli Of Rome
Roma, Italy
UO Gastroenterology, Policlinic Tor Vergata, Rome
Roma, Italy
UO Gastroenterology, University of Rome, Policlinic Sant'Andrea
Roma, Italy
UO Gastroenterology, Policlinic Umberto I Rome
Rome, Italy
Related Publications (6)
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. doi: 10.1016/j.jhep.2010.05.004. Epub 2010 Jun 1. No abstract available.
PMID: 20633946BACKGROUNDRunyon BA; AASLD Practice Guidelines Committee. Management of adult patients with ascites due to cirrhosis: an update. Hepatology. 2009 Jun;49(6):2087-107. doi: 10.1002/hep.22853. No abstract available.
PMID: 19475696BACKGROUNDQuinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology. 2005 Jun;41(6):1211-9. doi: 10.1002/hep.20720. No abstract available.
PMID: 15915465BACKGROUNDGentilini 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. doi: 10.1016/s0168-8278(99)80194-9.
PMID: 10207805BACKGROUNDRomanelli 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. doi: 10.3748/wjg.v12.i9.1403.
PMID: 16552809BACKGROUNDCaraceni P, Riggio O, Angeli P, Alessandria C, Neri S, Foschi FG, Levantesi F, Airoldi A, Boccia S, Svegliati-Baroni G, Fagiuoli S, Romanelli RG, Cozzolongo R, Di Marco V, Sangiovanni V, Morisco F, Toniutto P, Tortora A, De Marco R, Angelico M, Cacciola I, Elia G, Federico A, Massironi S, Guarisco R, Galioto A, Ballardini G, Rendina M, Nardelli S, Piano S, Elia C, Prestianni L, Cappa FM, Cesarini L, Simone L, Pasquale C, Cavallin M, Andrealli A, Fidone F, Ruggeri M, Roncadori A, Baldassarre M, Tufoni M, Zaccherini G, Bernardi M; ANSWER Study Investigators. Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. Lancet. 2018 Jun 16;391(10138):2417-2429. doi: 10.1016/S0140-6736(18)30840-7. Epub 2018 Jun 1.
PMID: 29861076DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mauro Bernardi, MD
University of Bologna
- STUDY DIRECTOR
Paolo Caraceni, MD
University of Bologna
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Full Professor of Medicine
Study Record Dates
First Submitted
February 1, 2011
First Posted
February 2, 2011
Study Start
March 1, 2011
Primary Completion
November 1, 2014
Study Completion
May 1, 2016
Last Updated
January 20, 2017
Record last verified: 2017-01