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The INFECIR-2 Albumin Prevention Study (INFECIR2)

Primary Purpose

Advanced Chronic Liver Disease, Urinary Infection, Pneumonia

Status

Terminated

Phase

Phase 4

Locations

Spain

Study Type

Interventional

Intervention

Albumin

About this trial

This is an interventional treatment trial for Advanced Chronic Liver Disease focused on measuring cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Hospital Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intravenous infusion of albumin

No albumin

Arm Description

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

Only antibiotics

Outcomes

Primary Outcome Measures

survival

Hospital survival will be the primary outcome

Secondary Outcome Measures

survival

Percentage of subjects within each arm that survived at these time points

Renal dysfunction

number of participants

circulatory dysfunction

plasma concentration of hormones

Inflammation and endothelial function

Plasma concentration of cytokines

subsequent organ failure

number of organ failures

Full Information

NCT ID

NCT02034279

First Posted

January 7, 2014

Last Updated

May 17, 2017

Sponsor

EASL - CLIF Consortium

1. Study Identification

Unique Protocol Identification Number

NCT02034279

Brief Title

The INFECIR-2 Albumin Prevention Study

Acronym

INFECIR2

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Terminated

Why Stopped

Low recruitment rate and expiration of the study drug

Study Start Date

May 2014 (Actual)

Primary Completion Date

December 31, 2016 (Actual)

Study Completion Date

February 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EASL - CLIF Consortium

4. Oversight

Data Monitoring Committee

Yes

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

cirrhosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

136 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intravenous infusion of albumin

Arm Type

Experimental

Arm Description

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

Arm Title

No albumin

Arm Type

No Intervention

Arm Description

Only antibiotics

Intervention Type

Drug

Intervention Name(s)

Albumin

Other Intervention Name(s)

Albutein 20 by Grifols

Intervention Description

Intravenous infusion of 20% albumin

Primary Outcome Measure Information:

Title

survival

Description

Hospital survival will be the primary outcome

Time Frame

hospitalization

Secondary Outcome Measure Information:

Title

survival

Description

Percentage of subjects within each arm that survived at these time points

Time Frame

28-d and 90-day survival

Title

Renal dysfunction

Description

number of participants

Time Frame

hospitalization (expected average 2 weeks)

Title

circulatory dysfunction

Description

plasma concentration of hormones

Time Frame

day 3 and day of infection resolution

Title

Inflammation and endothelial function

Description

Plasma concentration of cytokines

Time Frame

day of infection resolution

Title

subsequent organ failure

Description

number of organ failures

Time Frame

hospitalization (expected average 2 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials: