Patients with advanced cirrhosis (serum creatinine > 1.2 mg/dl, serum sodium 4 mg/dl), signs of systemic inflammation and urinary infection, pneumonia, skin/soft tissue infection, acute cholangitis or suspected bacterial infection will be included MedDRA version: 16.0 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 16.0 Level: LLT Classification code 10008954 Term: Chronic liver disease and cirrhosis System O
Conditions
Interventions
Trade Name: Albumin 20%
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Albumin
Other descriptive name: Human serum albumin
Concentration unit: % percent
Concentration type: equal
Conc
Sponsors
Fundacio Clinic per a la recerca biomedica
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age between 18 and 79 years. - Diagnosis of liver cirrhosis established by histology or by the combination of clinical, analytical and ultrasonographic data. - Clinical data of systemic inflammation indicated by the presence of at least 1 diagnostic criterion of SIRS and high serum CRP levels (> 2 mg/dL or 20 mg/L). - Diagnosis of urinary infection, pneumonia, skin/soft tissue infection, acute cholangitis or suspected bacterial infection at hospital admission or during hospitalization. Diagnostic criteria at inclusion will be the following: (a) urinary infections: more than 10 leukocytes per high-power field in urine or a positive reagent strip; (b) pneumonia: presence of new infiltrates on chest x-ray; (c) skin/soft tissue infection: physical exam findings of swelling, erythema, heat and tenderness in the skin; (d) acute cholangitis: cholestasis, compatible symptoms (right upper quadrant pain and jaundice) and radiological data of biliary obstruction and (e) suspected bacterial infection: signs of infection but no identifiable origin of this infection (polymorphonuclear cells in ascitic and pleural fluid 1.2 mg/dl, serum bilirubin > 4 mg/dl or serum sodium =65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: - > 48h after the diagnosis of infection. - Pregnancy. - Acute or subacute liver failure without underlying cirrhosis. - Septic shock (mean arterial pressure below 60 mmHg during more than 1 hour despite adequate fluid resuscitation and need of vasopressor drugs). - Acute respiratory distress syndrome [PaO2/Fi02 2.5 mg/dl). - Type-3 ACLF. - Intrinsic nephropathy (proteinuria, hematuria or abnormal findings on renal ultrasonography) with renal failure (serum creatinine chronically > 1.5 mg/dl). - Renal replacement therapy. - Arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 90 mmHg). - 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). - Severe pulmonary disease (GOLD III or IV). - Severe psychiatric disorders. - Any immunosuppressive drug. - HIV infection. - Contraindications to albumin (allergy, signs of pulmonary edema) - Administration of any dose of IV albumin in the last 10 days - Clinical indication for albumin use at inclusion (spontaneous bacterial peritonitis coinfection, large volume paracentesis) - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In hospital and 28-day mortality reduction in patients with advance cirrhosis, infection other than spontaneous bacterial peritonitis and high risk mortality;Secondary Objective: * 90-day survival * Incidence of renal dysfunction during hospitalization * Incidence of type-1 and type-2 HRS during hospitalization * Changes in plasma levels of renin and noradrenaline and in serum lactate levels during treatment of infection in both treatment arms * Changes in serum levels of IL-6, TNF-alpha and NOX and in plasma levels of vWF:Ag in both treatment arms * Changes in blood leukocyte count and serum CRP levels during treatment of infection in both treatment arms * Changes in CLIF-SOFA, CLIF-Consortium, CHILD-PUGH and MELD scores in both treatment arms * Incidence of new individual organ failures during hospitalization in both treatment arms * Incidence of ACLF (type 1, 2 and 3 according to the Canonic Study) during hospitalization in both treatment arms * Risk factors of HRS and ACLF in both treatment arms * Risk factors of short-term mortality in both treatment arms * Causes of death in both treatment arms * Length of hospital stay;Primary end point(s): Hospital and 28-day survival;Timepoint(s) of evaluation of this end point: day 3, day of infection resolution (or day 7 and every 7 days) and 28 day | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): * Effect of albumin administration on 90-day survival. * Effect of albumin infusion on the incidence of renal dysfunction, type-1 and type-2 HRS during hospitalization. * Effect of albumin on circulatory function estimated by changes in plasma levels of renin and noradrenaline and by changes in serum lactate levels among infection diagnosis, day 3 and infection resolution. * Effect of albumin on serum levels of IL-6, TNF-alpha and NOX and on plasma levels of vWF:Ag at infection diagnosis and at infection resolution. * Effect of albumin on blood leukocyte count and serum CPR levels during infection. * Effect of albumin infusion on the development of other individual organ failures (renal, liver, cerebral, circulatory, coagulation and respiratory) during hospitalization. * 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.;Timepoint(s) of evaluation of this end point: day 3, day of infection resolution (or day 7 and every 7 days) day 28 and day 90 | — |
Countries
Austria, Belgium, Denmark, France, Germany, Ireland, Italy, Netherlands, Norway, Spain, Switzerland, United Kingdom
Contacts
Public ContactFundacio Clinic
Fundacio Clinic per a la recerca biomedica
Outcome results
None listed