INFECIR2: The INFECIR-2 Albumin Prevention Study

Sponsor

EASL - CLIF Consortium (Other)

Overall Status

Terminated

CT.gov ID

NCT02034279

Collaborator

(none)

136

Enrollment

Location

Arms

33.4

Actual Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to evaluate whether albumin administration improves short-term survival in patients with advanced cirrhosis and bacterial infections other than Spontaneous Bacterial Peritonitis (SBP).

Condition or Disease	Intervention/Treatment	Phase
Advanced Chronic Liver Disease Urinary Infection Pneumonia Cholangitis Other Bacterial Diseases	Drug: Albumin	Phase 4

Detailed Description

The aim of this study is to evaluate if IV albumin administration improves short-term survival in patients with advanced cirrhosis (serum creatinine ≥ 1.2 mg/dl, serum sodium ≤ 130 mEq/l -milliequivalents per liter- and/or serum bilirubin ≥4 mg/dl) and bacterial infections other than spontaneous bacterial peritonitis (urinary infection, pneumonia, spontaneous or secondary bacteremia, skin/soft tissue infection, acute cholangitis or suspected bacterial infection).

Primary goals of the study:

• Effect of albumin administration on hospital survival

Secondary goals of the study:

Effect of albumin administration on 28-day and 90-day survival.
Effect of albumin administration on the incidence of renal dysfunction, AKI, type-1 and 2 Hepatorenal Syndrome (HRS) during hospitalization.
Effect of albumin on circulatory function estimated by changes in plasma levels of renin and noradrenaline and in serum levels of lactate among infection diagnosis, day 3 and infection resolution.
Effect of albumin on serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NOX) and on plasma levels of von Willebrand factor (vWF:Ag) at diagnosis and resolution of infection.
Effect of albumin on blood leukocyte count and serum C-reactive protein levels (CRP) during infection.
Effect of albumin on the development of other individual organ failures (renal, liver, cerebral, circulatory, coagulation and respiratory), acute-on-chronic liver failure (ACLF type 1, 2 and 3 according to the Canonic Study), CLIF-SOFA score, CLIF-Consortium score, Child-Pugh score and MELD score during hospitalization.
Evaluation of predictive factors of HRS and ACLF development in non-SBP infections.
Samples (blood, plasma, serum and urine) will be obtained and stored for genomic, proteomic and standard biochemical investigations in future ancillary studies related to the aim of the study.

Study Design

Study Type:

Interventional

Actual Enrollment :

136 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Albumin Administration in the Prevention of Hepatorenal Syndrome and Death in Patients With Cirrhosis, Bacterial Infections Other Than Spontaneous Bacterial Peritonitis and High Risk of Hospital Mortality

Actual Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Dec 31, 2016

Actual Study Completion Date :

Feb 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous infusion of albumin Treatment arm will receive intravenous albumin on days 1 and 3 plus antibiotics	Drug: Albumin Intravenous infusion of 20% albumin Other Names: Albutein 20 by Grifols
No Intervention: No albumin Only antibiotics

Arm

Intervention/Treatment

Experimental: Intravenous infusion of albumin

Treatment arm will receive intravenous albumin on days 1 and 3 plus antibiotics

Drug: Albumin

Intravenous infusion of 20% albumin

Other Names:

Albutein 20 by Grifols

No Intervention: No albumin

Only antibiotics

Outcome Measures

Primary Outcome Measures

survival [hospitalization]
Hospital survival will be the primary outcome

Secondary Outcome Measures

survival [28-d and 90-day survival]
Percentage of subjects within each arm that survived at these time points
Renal dysfunction [hospitalization (expected average 2 weeks)]
number of participants
circulatory dysfunction [day 3 and day of infection resolution]
plasma concentration of hormones
Inflammation and endothelial function [day of infection resolution]
Plasma concentration of cytokines
subsequent organ failure [hospitalization (expected average 2 weeks)]
number of organ failures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cirrhotic patients with age ≥18 years
Diagnosis of urinary infection, pneumonia, spontaneous or secondary bacteremia, skin/soft tissue infection, acute cholangitis or suspected bacterial infection at hospital admission or during hospitalization
Patients with uncomplicated urinary infections or suspected bacterial infection will require the presence of signs of systemic inflammation: at least 1 diagnostic criterion of systemic inflammatory response syndrome (SIRS) and serum CRP levels ≥1 mg/dl (10 mg/L). This criterion will not be required for the rest of infections
Analytical data of renal and/or liver dysfunction (serum creatinine ≥ 1.2 mg/dl, serum sodium ≤ 130 mEq/l, serum bilirubin ≥4 mg/dl). Patients with pneumonia or documented bacteremia (positive blood cultures) will require the presence of at least 1 of these analytical criteria to be included in the study. Patients with urinary infection, skin/soft tissue infection, acute cholangitis or suspected bacterial infection will require 2 or more criteria for inclusion

Exclusion Criteria:

72h after infection diagnosis
Pregnancy
Acute or subacute liver failure without underlying cirrhosis
Septic shock
Severe acute respiratory distress syndrome (Pa02/Fi02 ≤ 100)
Active or recent variceal bleeding unless controlled for > 48h
Ongoing type-1 HRS (past IAC criterion: serum creatinine ≥ 2.5 mg/dl)
Type-3 ACLF (defined according to the Canonic Study criteria)
Hemodialysis or other renal replacement therapy
Evidence of current malignancy (except for hepatocellular carcinoma within Milan criteria or non-melanocytic skin cancer)
Moderate or severe chronic heart (NYHA class II, III or IV) or pulmonary disease (GOLD IV)
Severe psychiatric disorders
Previous liver transplantation
HIV infection (except for patients under antiretroviral therapy with undetectable viral load, CD4>200/mm3 and no history of opportunistic infections diagnostic of AIDS)
Contraindications to albumin (allergy, signs of pulmonary edema)
Albumin administration (≥ 80g) in the last 2 days
Spontaneous bacterial peritonitis coinfection
Use of any investigational drug within 90 days prior to randomization
Refusal to participate
Patients who cannot provide prior informed consent and when there is documented evidence that the patient has no legal surrogate decision maker and it appears unlikely that the patient will regain consciousness or sufficient ability to provide delayed informed consent
Physician and team not committed to intensive care if needed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Clinic	Barcelona		Spain	08036

Sponsors and Collaborators

EASL - CLIF Consortium

Investigators

Principal Investigator: Thierry Gustot, Erasme University Hospital, Brussels, Belgium
Principal Investigator: Frederick Nevens, University Hospitals KU, Leuven, Belgium
Principal Investigator: Faouzi Saliba, Hôpital Paul Brousse, Villejuif, France
Principal Investigator: François Durand, Hôpital Beaujon, Clichy, France
Principal Investigator: Matthias Dollinger, University of Ulm, Heidelberg and Tübingen, Germany
Principal Investigator: Stefan Zeuzem, University Hospital of Frankfurt, Germany
Principal Investigator: Alexander Gerbes, University Hospital of Munich, Germany
Principal Investigator: Jonel Trebicka, University Hospital of Bonn, Germany
Principal Investigator: Henning Gronbaeck, Aarhus University Hospital, Aarhus, Denmark
Principal Investigator: Fin Stolze Larsen, Rigshospitalet, University of Copenhagen
Principal Investigator: John Willy Haukeland, Oslo University Hospital
Principal Investigator: Andrea de Gottardi, Bern University Hospital, Switzerland
Principal Investigator: Aide McCormick, University College of Dublin, Ireland
Principal Investigator: Rajiv Jalan, University College, London
Principal Investigator: Marco Domenicali, Santa Orsola-Malpighi Hospital, Bologna, Italy
Principal Investigator: Paolo Angeli, University of Padova, Italy
Principal Investigator: Carlo Alessandria, San Giovanni Battista Hospital, University of Turin, Italy
Principal Investigator: Francesco Salerno, Policlinico IRCCS San Donato, University of Milan, Italy
Principal Investigator: Agustin Albillos, Hospital Ramon y Cajal, Madrid, Spain
Principal Investigator: Victor Vargas, Hospital Vall d'Hebron, Barcelona, Spain
Principal Investigator: Javier Fernandez, Hospital Clinic, Barcelona, Spain
Principal Investigator: German Soriano, Hospital Santa Creu i Sant Pau, Barcelona, Spain
Principal Investigator: Rafael Bañares, Hospital Gregorio Marañon, Madrid, Spain
Principal Investigator: Jose Luis Montero, Hospital Reina Sofia, Cordoba, Spain
Principal Investigator: Manuela Merli, Sapienza University of Rome, Italy
Principal Investigator: Minneke Coenraad, Leiden University Medical Center
Principal Investigator: Rudolf Stauber, Medical University of Graz
Principal Investigator: Wolfgang Vogel, Medical Hospital Innsbrück