The INFECIR-2 Albumin Prevention Study

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Advanced Chronic Liver Disease, Urinary Infection, Pneumonia, Cholangitis, Other Bacterial Diseases

Intervention / Treatment
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* Drug: Albumin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous infusion of albumin<br>Treatment arm will receive intravenous albumin on days 1 and 3 plus antibiotics | Drug: Albumin<br>* Intravenous infusion of 20% albumin<br>* Other names: Albutein 20 by Grifols;|
| No Intervention: No albumin<br>Only antibiotics | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | Hospital survival will be the primary outcome | hospitalization | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cirrhosis