The INFECIR-2 Albumin Prevention Study

Pneumonia Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02034279
• Other study ID #: INFECIR 2
• Secondary ID: 2013-002416-27
• Status: Terminated
• Phase: Phase 4
• First received: January 7, 2014
• Last updated: May 17, 2017
• Start date: May 2014
• Est. completion date: February 10, 2017

Study information

• Verified date: May 2017
• Source: EASL - CLIF Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 136
• Est. completion date: February 10, 2017
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Chronic Liver Disease
• Bacterial Infections
• Cholangitis
• Infection
• Liver Diseases
• Other Bacterial Diseases
• Pneumonia
• Urinary Infection
• Urinary Tract Infections

Intervention

Drug:
• Albumin
Intravenous infusion of 20% albumin

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
EASL - CLIF Consortium

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Guevara M, Terra C, Nazar A, Solà E, Fernández J, Pavesi M, Arroyo V, Ginès P. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. J Hepatol. 2012 Oct;57(4):759-65. doi: 10.1016/j.jhep.2012.06.013. Epub 2012 Jun 23. — View Citation

Thévenot T, Bureau C, Oberti F, Anty R, Louvet A, Plessier A, Rudler M, Heurgué-Berlot A, Rosa I, Talbodec N, Dao T, Ozenne V, Carbonell N, Causse X, Goria O, Minello A, De Ledinghen V, Amathieu R, Barraud H, Nguyen-Khac E, Becker C, Paupard T, Botta-Fridlung D, Abdelli N, Guillemot F, Monnet E, Di Martino V. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. J Hepatol. 2015 Apr;62(4):822-30. doi: 10.1016/j.jhep.2014.11.017. Epub 2014 Nov 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	survival	Hospital survival will be the primary outcome	hospitalization
Secondary	survival	Percentage of subjects within each arm that survived at these time points	28-d and 90-day survival
Secondary	Renal dysfunction	number of participants	hospitalization (expected average 2 weeks)
Secondary	circulatory dysfunction	plasma concentration of hormones	day 3 and day of infection resolution
Secondary	Inflammation and endothelial function	Plasma concentration of cytokines	day of infection resolution
Secondary	subsequent organ failure	number of organ failures	hospitalization (expected average 2 weeks)

External Links

•   Web page of the INFECIR-2 RCT