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

Fingerprint

Albumins
Fibrosis
Therapeutics
Ascites
Pragmatic Clinical Trials
Intention to Treat Analysis
Survival
Mortality
Furosemide
Kaplan-Meier Estimate
Survival Analysis
Liver Cirrhosis
Research Personnel
Medicine
Pharmaceutical Preparations
Population

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

Cite this

Caraceni, P., Riggio, O., Angeli, P., Alessandria, C., Neri, S., Foschi, F. G., ... 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

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. / 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.; 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, F.M.; Cesarini, L.; Simone, L.; Pasquale, C.; Cavallin, M.; Andrealli, A.; Bernardi, M.; Risso, A.; Neri, E.; Visani, A.; Alberti, A.B.; Zappimbulso, M.; Auriemma, F.; Gasbarrini, antonio; Rossi, P.; Negri, E.; Conte, D.; Salerno, F.

In: The Lancet, Vol. 391, No. 10138, 2018, p. 2417-2429.

Research output: Contribution to journalArticle

Caraceni, 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, Bernardi, M, Risso, A, Neri, E, Visani, A, Alberti, AB, Zappimbulso, M, Auriemma, F, Gasbarrini, A, Rossi, P, Negri, E, Conte, D & Salerno, F 2018, 'Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial', The Lancet, vol. 391, no. 10138, pp. 2417-2429. https://doi.org/10.1016/S0140-6736(18)30840-7
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. ; 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, F.M. ; Cesarini, L. ; Simone, L. ; Pasquale, C. ; Cavallin, M. ; Andrealli, A. ; Bernardi, M. ; Risso, A. ; Neri, E. ; Visani, A. ; Alberti, A.B. ; Zappimbulso, M. ; Auriemma, F. ; Gasbarrini, antonio ; Rossi, P. ; Negri, E. ; Conte, D. ; Salerno, F. / Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial. In: The Lancet. 2018 ; Vol. 391, No. 10138. pp. 2417-2429.
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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. {\circledC} 2018 Elsevier Ltd",
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",
author = "P. Caraceni and O. Riggio and P. Angeli and C. Alessandria and S. Neri and F.G. Foschi and F. Levantesi and A. Airoldi and S. Boccia and G. Svegliati-Baroni and S. Fagiuoli and R.G. Romanelli and R. Cozzolongo and {Di Marco}, V. and V. Sangiovanni and F. Morisco and P. Toniutto and A. Tortora and {De Marco}, R. and M. Angelico and I. Cacciola and G. Elia and A. Federico and S. Massironi and R. Guarisco and A. Galioto and G. Ballardini and M. Rendina and S. Nardelli and S. Piano and C. Elia and L. Prestianni and F.M. Cappa and L. Cesarini and L. Simone and C. Pasquale and M. Cavallin and A. Andrealli and M. Bernardi and A. Risso and E. Neri and A. Visani and A.B. Alberti and M. Zappimbulso and F. Auriemma and antonio Gasbarrini and P. Rossi and E. Negri and D. Conte and F. Salerno",
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doi = "10.1016/S0140-6736(18)30840-7",
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TY - JOUR

T1 - Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

AU - Caraceni, P.

AU - Riggio, O.

AU - Angeli, P.

AU - Alessandria, C.

AU - Neri, S.

AU - Foschi, F.G.

AU - Levantesi, F.

AU - Airoldi, A.

AU - Boccia, S.

AU - Svegliati-Baroni, G.

AU - Fagiuoli, S.

AU - Romanelli, R.G.

AU - Cozzolongo, R.

AU - Di Marco, V.

AU - Sangiovanni, V.

AU - Morisco, F.

AU - Toniutto, P.

AU - Tortora, A.

AU - De Marco, R.

AU - Angelico, M.

AU - Cacciola, I.

AU - Elia, G.

AU - Federico, A.

AU - Massironi, S.

AU - Guarisco, R.

AU - Galioto, A.

AU - Ballardini, G.

AU - Rendina, M.

AU - Nardelli, S.

AU - Piano, S.

AU - Elia, C.

AU - Prestianni, L.

AU - Cappa, F.M.

AU - Cesarini, L.

AU - Simone, L.

AU - Pasquale, C.

AU - Cavallin, M.

AU - Andrealli, A.

AU - Bernardi, M.

AU - Risso, A.

AU - Neri, E.

AU - Visani, A.

AU - Alberti, A.B.

AU - Zappimbulso, M.

AU - Auriemma, F.

AU - Gasbarrini, antonio

AU - Rossi, P.

AU - Negri, E.

AU - Conte, D.

AU - Salerno, F.

N1 - cited By 19

PY - 2018

Y1 - 2018

N2 - 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

AB - 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

KW - aldosterone antagonist

KW - furosemide

KW - human albumin

KW - albuminoid

KW - diuretic agent

KW - mineralocorticoid antagonist, adult

KW - age

KW - all cause mortality

KW - allergic reaction

KW - Article

KW - ascites

KW - bacterial infection

KW - bacterial peritonitis

KW - breast disease

KW - Child Pugh score

KW - connective tissue disease

KW - controlled study

KW - cost effectiveness analysis

KW - decompensated liver cirrhosis

KW - dizziness

KW - end stage liver disease

KW - erythema

KW - eye disease

KW - female

KW - gastrointestinal disease

KW - genital system disease

KW - heart disease

KW - hematologic disease

KW - hepatic encephalopathy

KW - hepatorenal syndrome

KW - hospital admission

KW - human

KW - hyperkalemia

KW - hyponatremia

KW - hypotension

KW - injury

KW - intoxication

KW - Italy

KW - kidney disease

KW - kidney dysfunction

KW - liver transplantation

KW - lymphatic system disease

KW - major clinical study

KW - male

KW - mental disease

KW - metabolic disorder

KW - Model For End Stage Liver Disease Score

KW - multicenter study

KW - musculoskeletal disease

KW - neoplasm

KW - neurologic disease

KW - nutritional disorder

KW - open study

KW - overall survival

KW - paracentesis

KW - parallel design

KW - pragmatic trial

KW - priority journal

KW - pruritus

KW - quality adjusted life year

KW - quality of life

KW - randomized controlled trial

KW - sepsis

KW - survival time

KW - transjugular intrahepatic portosystemic shunt

KW - urinary tract disease

KW - vascular disease

KW - aged

KW - chemically induced

KW - clinical trial

KW - combination drug therapy

KW - complication

KW - Kaplan Meier method

KW - liver cirrhosis

KW - middle aged

KW - pathophysiology

KW - survival rate

KW - time factor, Aged

KW - Albumins

KW - Ascites

KW - Diuretics

KW - Drug Therapy, Combination

KW - Female

KW - Furosemide

KW - Humans

KW - Hyperkalemia

KW - Hyponatremia

KW - Kaplan-Meier Estimate

KW - Liver Cirrhosis

KW - Male

KW - Middle Aged

KW - Mineralocorticoid Receptor Antagonists

KW - Paracentesis

KW - Quality of Life

KW - Quality-Adjusted Life Years

KW - Survival Rate

KW - Time Factors

U2 - 10.1016/S0140-6736(18)30840-7

DO - 10.1016/S0140-6736(18)30840-7

M3 - Article

VL - 391

SP - 2417

EP - 2429

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10138

ER -