Project description
DEENESFRITPL
Combinatorial therapy for decompensated cirrhosis
Cirrhosis mortality is mainly associated with cirrhosis decompensation (development of ascites, hepatic encephalopathy, gastrointestinal haemorrhage, and progression to acute-on-chronic liver failure (ACLF). Despite multiple treatments, mortality in patients with decompensation of cirrhosis remains high. The EU-funded DECISION project aims to understand the pathophysiology of decompensation of cirrhosis leading to ACLF or death, and to decrease patient mortality. The project will study the pathophysiology of decompensation of cirrhosis by integrating results of high-throughput multi-omic profiling with comprehensive clinical data from 2 200 fully characterised patients with available standardised biological samples. DECISION will help to identify novel combinatorial therapies to prevent high mortality for patients with decompensation of cirrhosis. Finally, researchers will optimise these therapies in new animal models and then test the best combination in high-risk patients in a Phase II clinical trial.
Objective
In 2013, cirrhosis was responsible for 1.2 million deaths worldwide. This mortality is mainly due to cirrhosis decompensation, i.e. development of ascites, hepatic encephalopathy, and/or gastrointestinal hemorrhage, and its progression to acute-on-chronic liver failure (ACLF). Patients with decompensated cirrhosis receive many treatments such as intravenous and oral absorbable antibiotics, oral non-absorbable antibiotics, albumin, proton-pump inhibitors, laxatives, diuretics, betablockers, vasoconstrictors, statins, anticoagulants, steroids and antiviral agents. Despite these multiple treatments, ACLF or mortality in patients with decompensation of cirrhosis remains high (15% at day 28, 28% at day 90) because of large interindividual variability in precipitating events, in clinical presentation and in response to treatment. This heterogeneity calls for treatment personalization according to underlying mechanisms. The objective of DECISION is to enhance our understanding, at systems level, of the pathophysiology of decompensation of cirrhosis leading to ACLF or death to decrease patients’ mortality at day 28.
First, DECISION will improve our knowledge of the pathophysiology of decompensation of cirrhosis by integrating results of high-throughput multi-omic profiling with comprehensive clinical data from 2,200 fully characterized patients (more than 8,600 time points) with available standardized biological samples. Second, we will identify novel combinatorial therapies for patients with decompensation of cirrhosis to prevent death. We will refine these therapies in new and/or optimized animal models and then test the best combination in high risk patients in a phase II clinical trial built in DECISION. Third, we will develop 2 tests: one predicting outcome of patients with decompensation of cirrhosis when treated with standard treatment (prognostic test); and the other identifying patients who will respond to the novel combinatorial therapy (test for response).
Fields of science
- social sciencessociologydemographymortality
- medical and health sciencesbasic medicinephysiologypathophysiology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesclinical medicinehepatology
Keywords
- cirrhosis
- decompensation of cirrhosis
- survival
- combinatorial therapy
- infection
- omics
Programme(s)
- H2020-EU.3.1. - SOCIETAL CHALLENGES - Health, demographic change and well-being Main Programme
- H2020-EU.3.1.1. - Understanding health, wellbeing and disease
Topic(s)
- SC1-BHC-02-2019 - Systems approaches for the discovery of combinatorial therapies for complex disorders
Call for proposal
H2020-SC1-BHC-2018-2020
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Sub call
H2020-SC1-2019-Two-Stage-RTD
Funding Scheme
RIA - Research and Innovation action
Coordinator
EUROPEAN FOUNDATION FOR THE STUDY OF CHRONIC LIVER FAILURE (EF-CLIF)
Net EU contribution
€ 1 233 650,00
Address
TRAVESSERA DE GRACIA 11, 7TH FLOOR
08021 Barcelona
Spain
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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost
€ 1 233 650,00
Participants (25)
FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Spain
Net EU contribution
€ 326 818,00
Address
CARRER ROSSELLO 149
08036 Barcelona
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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
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Total cost
€ 371 723,13
Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
HOSPITAL CLINIC DE BARCELONA
Spain
Net EU contribution
€ 44 904,00
Address
CALLE VILLARROEL 170
08036 Barcelona
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Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
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Total cost
€ 44 905,00
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Netherlands
Net EU contribution
€ 300 000,00
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
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Region
West-Nederland Zuid-Holland Groot-Rijnmond
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 300 000,00
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Net EU contribution
€ 578 738,75
Address
RUE DE TOLBIAC 101
75654 Paris
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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
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Total cost
€ 620 500,00
Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
UNIVERSITE PARIS CITE
France
Net EU contribution
€ 41 761,25
Address
85 BD SAINT GERMAIN
75006 Paris
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Region
Ile-de-France Ile-de-France Paris
Activity type
Higher or Secondary Education Establishments
Links
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JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Participation ended
Germany
Net EU contribution
€ 257 692,00
Address
THEODOR W ADORNO PLATZ 1
60323 Frankfurt Am Main
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Region
Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 257 692,93
UNIVERSITAETSKLINIKUM AACHEN
Germany
Net EU contribution
€ 275 874,00
Address
Pauwelsstrasse 30
52074 Aachen
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Region
Nordrhein-Westfalen Köln Städteregion Aachen
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 275 874,38
COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
France
Net EU contribution
€ 345 000,00
Address
RUE LEBLANC 25
75015 PARIS 15
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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
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Total cost
€ 345 000,00
FUNDACION PUBLICA MIGUEL SERVET
Spain
Net EU contribution
€ 382 500,00
Address
CALLE IRUNLARREA 3 CENTRO INVESTIGACION BIOMEDICA RECINTO COMPLEJO HOSPITALARIO DE NAVARRA
31008 Pamplona
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Region
Noreste Comunidad Foral de Navarra Navarra
Activity type
Research Organisations
Links
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Total cost
€ 382 500,00
YH YOUHEALTH AB
Sweden
Net EU contribution
€ 260 000,00
Address
FOGDEVRETEN 2 KAROLINSKA SCIENCE
171 77 Stockholm
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SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
Yes
Region
Östra Sverige Stockholm Stockholms län
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
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Total cost
€ 260 000,00
NORDIC BIOSCIENCE A/S
Denmark
Net EU contribution
€ 66 043,00
Address
HERLEV HOVEDGADE 205-207
2730 Herlev
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SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
Yes
Region
Danmark Hovedstaden Københavns omegn
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
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Total cost
€ 66 043,00
ALMA MATER STUDIORUM - UNIVERSITA DI BOLOGNA
Italy
Net EU contribution
€ 161 898,00
Address
VIA ZAMBONI 33
40126 Bologna
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Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 171 723,75
Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
IRCCS AZIENDA OSPEDALIERO- UNIVERSITARIA DI BOLOGNA
Italy
Net EU contribution
€ 9 824,00
Address
VIA ALBERTONI 15
40138 Bologna
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Region
Nord-Est Emilia-Romagna Bologna
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Links
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Total cost
€ 9 825,00
SERVICIO MADRILENO DE SALUD
Spain
Net EU contribution
€ 105 472,00
Address
Paseo De la Castellana, 280
28046 MADRID
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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Links
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Total cost
€ 105 472,50
UNIVERSITY COLLEGE LONDON
United Kingdom
Net EU contribution
€ 105 879,00
Address
GOWER STREET
WC1E 6BT London
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Region
London Inner London — West Camden and City of London
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 105 879,13
UNIVERSITA DEGLI STUDI DI PADOVA
Italy
Net EU contribution
€ 42 500,00
Address
VIA 8 FEBBRAIO 2
35122 Padova
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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 42 500,00
UNIVERSITA DEGLI STUDI DI TORINO
Italy
Net EU contribution
€ 75 472,00
Address
VIA GIUSEPPE VERDI 8
10124 Torino
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Region
Nord-Ovest Piemonte Torino
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 105 472,50
Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
AZIENDA OSPEDALIERA CITTA DELLA SALUTE E DELLA SCIENZA DI TORINO
Italy
Net EU contribution
€ 30 000,00
Address
CORSO BRAMANTE 88 90
10126 Torino
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Region
Nord-Ovest Piemonte Torino
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Links
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Total cost
€ 30 000,00
INSTITUT CATALA DE LA SALUT
Spain
Net EU contribution
€ 105 472,00
Address
GRAN VIA DE LES CORTS CATALANES 587
08007 Barcelona
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Region
Este Cataluña Barcelona
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Links
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Total cost
€ 105 472,50
UNIVERSITAT DE BARCELONA
Spain
Net EU contribution
€ 120 000,00
Address
GRAN VIA DE LES CORTS CATALANES 585
08007 Barcelona
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Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 120 000,00
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
France
Net EU contribution
€ 420 472,00
Address
55 BOULEVARD DIDEROT
75012 Paris
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Region
Ile-de-France Ile-de-France Val-de-Marne
Activity type
Research Organisations
Links
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Total cost
€ 420 472,50
EUROPEAN ASSOCIATION FOR THE STUDYOF THE LIVER
Switzerland
Net EU contribution
€ 50 000,00
Address
RUE DAUBIN 7
1203 Geneve
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Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Other
Links
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Total cost
€ 50 000,00
EUROPEAN LIVER PATIENTS ASSOCIATION
Belgium
Net EU contribution
€ 50 000,00
Address
PLACE DU CHAMPS DE MARS 5
1050 Bruxelles / Brussel
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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
Activity type
Other
Links
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Total cost
€ 50 000,00
CONCENTRIS RESEARCH MANAGEMENT GMBH
Germany
Net EU contribution
€ 488 500,00
Address
Ludwigstr. 4
82256 FURSTENFELDBRUCK
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SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
Yes
Region
Bayern Oberbayern Fürstenfeldbruck
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Links
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Total cost
€ 488 500,00
UNIVERSITAET MUENSTER
Germany
Net EU contribution
€ 121 530,00
Address
SCHLOSSPLATZ 2
48149 MUENSTER
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Region
Nordrhein-Westfalen Münster Münster, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
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Total cost
€ 121 530,81
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Last update: 1 April 2024
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Permalink: https://cordis.europa.eu/project/id/847949
European Union, 2024