bacterial infection cirrose scarring of the liver
Conditions
Interventions
After enrollment in this study, patients will be randomly assigned to one of
the two study groups (antibiotics+albumin vs. antibiotics alone) in a 1:1
ratio. Randomization will be centralized, perfo
albumin
cirrhosis
hepatorenal syndrome
infection
Sponsors
CLIF CONSORTIUM, Liver Unit, Hospital Clinic
Eligibility
Age
18 Years to 64 Years
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 < 250/mm3, normal urine sediment and chest X-ray).;- Presence of renal and/or liver dysfunction (serum creatinine *1.2 mg/dl, serum bilirubin *4 mg/dl or serum sodium * 130 mEq/l). Patients with pneumonia will require the presence of at least 1 of these analytical criteria to be included in the study. Two or more criteria will be required in patients with urinary infection, skin/soft tissue infection, acute cholangitis or suspected bacterial infection.
Exclusion criteria
Exclusion criteria: - > 48h after the diagnosis of infection.;- Pre-menopausal women (last menstruation * 12 months prior to enrolment) who are nursing or pregnant or are of child bearing potential and are not practicing an acceptable method of birth control.;- 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 *200 or a pulse oximetric saturation (SpO2) to FiO2 ratio *214].;- Gastrointestinal bleeding in the last 5 days.;- Biopsy proven severe acute alcoholic hepatitis requiring specific treatment. ;- Type-1 HRS (IAC criteria: serum creatinine * 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 or albumin dialysis 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.;All patients meeting the inclusion criteria will be entered on a screening log. If the patient is not enrolled, the screening log will include information explaining why enrollment did not occur.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary study outcomes: * Hospital and 28-day survival in both treatment arms | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcomes: * 90-day survival in both treatment arms * Incidence of renal dysfunction during hospitalization in both treatment arms * Incidence of type-1 and type-2 HRS during hospitalization in both treatment arms * 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 | — |
Countries
Spain
Outcome results
None listed