Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

P. Caraceni, O. Riggio, P. Angeli, C. Alessandria, S. Neri, F.G. Foschi, F. Levantesi, A. Airoldi, S. Boccia, G. Svegliati-Baroni, S. Fagiuoli, R.G. Romanelli, R. Cozzolongo, V. Di Marco, V. Sangiovanni, F. Morisco, P. Toniutto, A. Tortora, R. De Marco, M. AngelicoI. Cacciola, G. Elia, A. Federico, S. Massironi, R. Guarisco, A. Galioto, G. Ballardini, M. Rendina, S. Nardelli, S. Piano, C. Elia, L. Prestianni, F.M. Cappa, L. Cesarini, L. Simone, C. Pasquale, M. Cavallin, A. Andrealli, M. Bernardi, A. Risso, E. Neri, A. Visani, A.B. Alberti, M. Zappimbulso, F. Auriemma, antonio Gasbarrini, P. Rossi, E. Negri, D. Conte, F. Salerno

Research output: Contribution to journalArticle

Abstract

Background: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008–000625–19, and ClinicalTrials.gov, number NCT01288794. Findings: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40–0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3–4 non-liver related adverse events. Interpretation: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Funding: Italian Medicine Agency. © 2018 Elsevier Ltd
Original languageEnglish
Pages (from-to)2417-2429
Number of pages13
JournalThe Lancet
Volume391
Issue number10138
DOIs
Publication statusPublished - 2018

Keywords

  • aldosterone antagonist
  • furosemide
  • human albumin
  • albuminoid
  • diuretic agent
  • mineralocorticoid antagonist, adult
  • age
  • all cause mortality
  • allergic reaction
  • Article
  • ascites
  • bacterial infection
  • bacterial peritonitis
  • breast disease
  • Child Pugh score
  • connective tissue disease
  • controlled study
  • cost effectiveness analysis
  • decompensated liver cirrhosis
  • dizziness
  • end stage liver disease
  • erythema
  • eye disease
  • female
  • gastrointestinal disease
  • genital system disease
  • heart disease
  • hematologic disease
  • hepatic encephalopathy
  • hepatorenal syndrome
  • hospital admission
  • human
  • hyperkalemia
  • hyponatremia
  • hypotension
  • injury
  • intoxication
  • Italy
  • kidney disease
  • kidney dysfunction
  • liver transplantation
  • lymphatic system disease
  • major clinical study
  • male
  • mental disease
  • metabolic disorder
  • Model For End Stage Liver Disease Score
  • multicenter study
  • musculoskeletal disease
  • neoplasm
  • neurologic disease
  • nutritional disorder
  • open study
  • overall survival
  • paracentesis
  • parallel design
  • pragmatic trial
  • priority journal
  • pruritus
  • quality adjusted life year
  • quality of life
  • randomized controlled trial
  • sepsis
  • survival time
  • transjugular intrahepatic portosystemic shunt
  • urinary tract disease
  • vascular disease
  • aged
  • chemically induced
  • clinical trial
  • combination drug therapy
  • complication
  • Kaplan Meier method
  • liver cirrhosis
  • middle aged
  • pathophysiology
  • survival rate
  • time factor, Aged
  • Albumins
  • Ascites
  • Diuretics
  • Drug Therapy, Combination
  • Female
  • Furosemide
  • Humans
  • Hyperkalemia
  • Hyponatremia
  • Kaplan-Meier Estimate
  • Liver Cirrhosis
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists
  • Paracentesis
  • Quality of Life
  • Quality-Adjusted Life Years
  • Survival Rate
  • Time Factors

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  • Cite this

    Caraceni, P., Riggio, O., Angeli, P., Alessandria, C., Neri, S., Foschi, F. G., Levantesi, F., Airoldi, A., Boccia, S., Svegliati-Baroni, G., Fagiuoli, S., Romanelli, R. G., Cozzolongo, R., Di Marco, V., Sangiovanni, V., Morisco, F., Toniutto, P., Tortora, A., De Marco, R., ... Salerno, F. (2018). Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. The Lancet, 391(10138), 2417-2429. https://doi.org/10.1016/S0140-6736(18)30840-7