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.

Phase 1

Conditions: Male and female cirrhotic patients with advanced cirrhosis (serum creatinine = 1.2 mg/dl, serum sodium = 130 mEq/l and/or serum bilirubin =4 mg/dl), and 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.
MedDRA version: 18.1Level: LLTClassification code 10008954Term: Chronic liver disease and cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders
MedDRA version: 18.1Level: LLTClassification code 10024667Term: Liver cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders
MedDRA version: 18.1Level: PTClassification code 10019641Term: Hepatic cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders
MedDRA version: 18.1Level: LLTClassification code 10064704Term: Decompensated cirrhosisSystem Organ Class: 10019805 - Hepatobiliary disorders
MedDRA version: 18.1Level: LLTClassification code 10009213Term: Cirrhosis of liverSystem Organ Class: 10019805 - Hepatobiliary disorders
MedDRA version: 18.1Level: LLTClassification code 10009211Term: Cirrhosis liverSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2013-002416-27-DE

Lead Sponsor: Fundacio Clinic per a la Recerca Biomedica

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 512

Inclusion Criteria

1. Male and female patients with age = 18 years.
2. Diagnosis of liver cirrhosis established by histology or by the combination of clinical, analytical and ultrasonographic data.
3. 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.
Diagnostic criteria at inclusion will be the following:
(a) Urinary infections: signs of systemic inflammation (described in criterion number 4) and more than 10 leukocytes per high-power field in urine or a positive reagent strip;
(b) Pneumonia: signs of infection (described below) and presence of new infiltrates on chest x-ray;
(c) Skin/soft tissue infection: signs of infection and physical exam findings of swelling, erythema, heat and tenderness in the skin;
(d) Acute cholangitis: signs of infection and cholestasis, compatible symptoms (right upper quadrant pain and jaundice) and radiological data of biliary obstruction;
(e) Spontaneous bacteremia: positive blood cultures and no cause of bacteremia;
(f) Secondary bacteremia: positive blood and catheter cultures or bacteremia within 24h after invasive procedure;
(g) Suspected bacterial infection: signs of systemic inflammation (described in criterion number 4) but no identifiable origin of this infection (polymorphonuclear cells in ascitic and pleural fluid < 250/mm3, normal urine sediment and chest X-ray).
4. Patients with uncomplicated urinary infections or suspected bacterial infections will require the presence of signs of systemic inflammation: at least 1 diagnostic criterion of systemic inflammatory response syndrome (SIRS) and high serum CRP levels (=1 mg/dL or 10 mg/L). This criterion will not be required for the rest of infections.
5. Analytical data of renal and/or liver dysfunction (serum creatinine =1.2 mg/dl, serum sodium =130 mEq/l or 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 362
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

1. More than 72h after infection diagnosis.
2. 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. The methods considered as acceptable are: intrauterine devices, double barrier method (condom or diaphragm with spermicide), hormonal methods (oral contraceptive, contraceptive patch, long-acting injectable contraceptive) and tubal ligation.
3. Acute or sub-acute liver failure without underlying cirrhosis.
4. Septic shock (mean arterial pressure below 60 mmHg during more than 1 hour despite adequate fluid resuscitation and need of vasopressor drugs).
5. Severe acute respiratory distress syndrome [PaO2/Fi02 =100 or a pulse oximetric saturation (SpO2) to FiO2 ratio =89].
6. Active or recent variceal bleeding (unless controlled for > 48h).
7. Ongoing type-1 HRS (IAC criteria; serum creatinine = 2.5 mg/dl).
8. Type-3 ACLF (defined according to the Canonic Study criteria).
9. Hemodialysis or other type of renal replacement therapy.
10. Evidence of current malignancy (except for hepatocellular carcinoma within Milan criteria or non-melanocytic skin cancer).
11. Previously known moderate or severe chronic heart failure (NYHA class II, III or IV).
12. Previously known severe chronic pulmonary disease (GOLD IV).
13. Previously known severe psychiatric disorders that prevent the patient from giving informed consent and from making autonomous decisions.
14. Previous liver transplantation.
15. Previously known HIV infection (except for patients under antiretroviral therapy with undetectable viral load, CD4 levels > 200/mm3 and no previous history of opportunistic infections diagnostic of AIDS).
16. Contraindications to albumin (allergy, signs of pulmonary edema).
17. Albumin administration (= 80 g) in the last 2 days.
18. Spontaneous bacterial peritonitis co-infection.
19. Usage of any investigational drug within 90 days prior to randomization or the planned use of an investigational drug during the course of the current study.
20. Refusal to participate.
21. 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.
22. Physician and team not committed to intensive care if needed.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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