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

Paolo Caraceni, Oliviero Riggio, Paolo Angeli, Carlo Alessandria, Sergio Neri, Francesco G. Foschi, Fabio Levantesi, Aldo Airoldi, Sergio Boccia, Gianluca Svegliati-Baroni, Stefano Fagiuoli, Roberto G. Romanelli, Raffaele Cozzolongo, Vito Di Marco, Vincenzo Sangiovanni, Filomena Morisco, Pierluigi Toniutto, Annalisa Tortora, Rosanna De Marco, Mario AngelicoIrene Cacciola, Gianfranco Elia, Alessandro Federico, Sara Massironi, Riccardo Guarisco, Alessandra Galioto, Giorgio Ballardini, Maria Rendina, Silvia Nardelli, Salvatore Piano, Chiara Elia, Loredana Prestianni, Federica Mirici Cappa, Lucia Cesarini, Loredana Simone, Chiara Pasquale, Marta Cavallin, Alida Andrealli, Federica Fidone, Matteo Ruggeri, Andrea Roncadori, Maurizio Baldassarre, Manuel Tufoni, Giacomo Zaccherini, Mauro Bernardi, Marco Domenicali, Ferdinando A. Giannone, Francesco Auriemma, Dario Conte, Francesco Salerno

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2417-2429
JournalThe Lancet
Volume391
Issue number10138
DOIs
Publication statusPublished - 2018

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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

ASJC Scopus subject areas

  • Medicine(all)

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, Paolo; Riggio, Oliviero; Angeli, Paolo; Alessandria, Carlo; Neri, Sergio; Foschi, Francesco G.; Levantesi, Fabio; Airoldi, Aldo; Boccia, Sergio; Svegliati-Baroni, Gianluca; Fagiuoli, Stefano; Romanelli, Roberto G.; Cozzolongo, Raffaele; Di Marco, Vito; Sangiovanni, Vincenzo; Morisco, Filomena; Toniutto, Pierluigi; Tortora, Annalisa; De Marco, Rosanna; Angelico, Mario; Cacciola, Irene; Elia, Gianfranco; Federico, Alessandro; Massironi, Sara; Guarisco, Riccardo; Galioto, Alessandra; Ballardini, Giorgio; Rendina, Maria; Nardelli, Silvia; Piano, Salvatore; Elia, Chiara; Prestianni, Loredana; Cappa, Federica Mirici; Cesarini, Lucia; Simone, Loredana; Pasquale, Chiara; Cavallin, Marta; Andrealli, Alida; Fidone, Federica; Ruggeri, Matteo; Roncadori, Andrea; Baldassarre, Maurizio; Tufoni, Manuel; Zaccherini, Giacomo; Bernardi, Mauro; Domenicali, Marco; Giannone, Ferdinando A.; Auriemma, Francesco; Conte, Dario; Salerno, Francesco.

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, Fidone, F, Ruggeri, M, Roncadori, A, Baldassarre, M, Tufoni, M, Zaccherini, G, Bernardi, M, Domenicali, M, Giannone, FA, Auriemma, F, 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, Paolo ; Riggio, Oliviero ; Angeli, Paolo ; Alessandria, Carlo ; Neri, Sergio ; Foschi, Francesco G. ; Levantesi, Fabio ; Airoldi, Aldo ; Boccia, Sergio ; Svegliati-Baroni, Gianluca ; Fagiuoli, Stefano ; Romanelli, Roberto G. ; Cozzolongo, Raffaele ; Di Marco, Vito ; Sangiovanni, Vincenzo ; Morisco, Filomena ; Toniutto, Pierluigi ; Tortora, Annalisa ; De Marco, Rosanna ; Angelico, Mario ; Cacciola, Irene ; Elia, Gianfranco ; Federico, Alessandro ; Massironi, Sara ; Guarisco, Riccardo ; Galioto, Alessandra ; Ballardini, Giorgio ; Rendina, Maria ; Nardelli, Silvia ; Piano, Salvatore ; Elia, Chiara ; Prestianni, Loredana ; Cappa, Federica Mirici ; Cesarini, Lucia ; Simone, Loredana ; Pasquale, Chiara ; Cavallin, Marta ; Andrealli, Alida ; Fidone, Federica ; Ruggeri, Matteo ; Roncadori, Andrea ; Baldassarre, Maurizio ; Tufoni, Manuel ; Zaccherini, Giacomo ; Bernardi, Mauro ; Domenicali, Marco ; Giannone, Ferdinando A. ; Auriemma, Francesco ; Conte, Dario ; Salerno, Francesco. / 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.",
author = "Paolo Caraceni and Oliviero Riggio and Paolo Angeli and Carlo Alessandria and Sergio Neri and Foschi, {Francesco G.} and Fabio Levantesi and Aldo Airoldi and Sergio Boccia and Gianluca Svegliati-Baroni and Stefano Fagiuoli and Romanelli, {Roberto G.} and Raffaele Cozzolongo and {Di Marco}, Vito and Vincenzo Sangiovanni and Filomena Morisco and Pierluigi Toniutto and Annalisa Tortora and {De Marco}, Rosanna and Mario Angelico and Irene Cacciola and Gianfranco Elia and Alessandro Federico and Sara Massironi and Riccardo Guarisco and Alessandra Galioto and Giorgio Ballardini and Maria Rendina and Silvia Nardelli and Salvatore Piano and Chiara Elia and Loredana Prestianni and Cappa, {Federica Mirici} and Lucia Cesarini and Loredana Simone and Chiara Pasquale and Marta Cavallin and Alida Andrealli and Federica Fidone and Matteo Ruggeri and Andrea Roncadori and Maurizio Baldassarre and Manuel Tufoni and Giacomo Zaccherini and Mauro Bernardi and Marco Domenicali and Giannone, {Ferdinando A.} and Francesco Auriemma and Dario Conte and Francesco Salerno",
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TY - JOUR

T1 - Long-term albumin administration in decompensated cirrhosis (ANSWER)

T2 - an open-label randomised trial

AU - Caraceni, Paolo

AU - Riggio, Oliviero

AU - Angeli, Paolo

AU - Alessandria, Carlo

AU - Neri, Sergio

AU - Foschi, Francesco G.

AU - Levantesi, Fabio

AU - Airoldi, Aldo

AU - Boccia, Sergio

AU - Svegliati-Baroni, Gianluca

AU - Fagiuoli, Stefano

AU - Romanelli, Roberto G.

AU - Cozzolongo, Raffaele

AU - Di Marco, Vito

AU - Sangiovanni, Vincenzo

AU - Morisco, Filomena

AU - Toniutto, Pierluigi

AU - Tortora, Annalisa

AU - De Marco, Rosanna

AU - Angelico, Mario

AU - Cacciola, Irene

AU - Elia, Gianfranco

AU - Federico, Alessandro

AU - Massironi, Sara

AU - Guarisco, Riccardo

AU - Galioto, Alessandra

AU - Ballardini, Giorgio

AU - Rendina, Maria

AU - Nardelli, Silvia

AU - Piano, Salvatore

AU - Elia, Chiara

AU - Prestianni, Loredana

AU - Cappa, Federica Mirici

AU - Cesarini, Lucia

AU - Simone, Loredana

AU - Pasquale, Chiara

AU - Cavallin, Marta

AU - Andrealli, Alida

AU - Fidone, Federica

AU - Ruggeri, Matteo

AU - Roncadori, Andrea

AU - Baldassarre, Maurizio

AU - Tufoni, Manuel

AU - Zaccherini, Giacomo

AU - Bernardi, Mauro

AU - Domenicali, Marco

AU - Giannone, Ferdinando A.

AU - Auriemma, Francesco

AU - Conte, Dario

AU - Salerno, Francesco

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.

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.

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