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 and/or serum bilirubin *4 mg/dl), signs of systemic…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Ancillary infectious topics
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary study outcomes:
* Hospital and 28-day survival in both treatment arms
Secondary outcome
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
Background summary
Bacterial infections other than spontaneaous bacterial peritonitis (SBP) are
common complications in cirrhosis. The
beneficial effect of albumin has been clearly proved in SBP (15%-30% of all
infections) because it reduces the incidence of type-1 hepatorenal syndrome
(HRS) and hospital mortality.However, thepotential benefit of albumin in
non-SBP infections is unclear.
The study will be performed by the European Association for the Study of the
Liver Chronic Liver Failure Consortium (EASL-CLIF Consortium). The EASL-CLIF
Consortium is a non-profit organization created by the initiative of several
European investigators and the European Association for the Study of the Liver
(EASL) in February 2009.
Study objective
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 and/or serum bilirubin *4 mg/dl), signs of
systemic inflammation and bacterial infections other than spontaneous bacterial
peritonitis (urinary infection, pneumonia, skin/soft tissue infection, acute
cholangitis or suspected bacterial infection).
*
Study design
Phase IV, open-label, multicenter European RCT involving liver units with
expertise in management of patients with decompensated liver cirrhosis.
Patients with advanced cirrhosis (serum creatinine * 1.2 mg/dl, serum sodium *
130 mEq/l and/or serum bilirubin *4 mg/dl), signs of systemic inflammation and
urinary infection, pneumonia, skin/soft tissue infection, acute cholangitis or
suspected bacterial infection will be included. Patients will be randomized
into two groups at the time of the diagnosis of infection:
* Standard medical therapy (antibiotics)
* Standard medical therapy plus IV albumin (albumin group)
Intervention
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, performed on line after patient
inclusion and stratified according to the type of infection (pneumonia vs.
other infections) and the site of acquisition of the infection (CA or HCA vs.
nosocomial).
DOSING REGIMEN
In patients assigned to the albumin group, intravenous albumin (20% albumin
Grifols) will be administered at a dose of 1.5 g/kg body weight at day 1 (day
of inclusion) and 1 g/kg body weight at day 3 up to a maximum of 150 g and 100
g, respectively, in patients with body weight over 100 kg and a minimum of 90g
and 60 g, respectively in patients with body weight lower than 60 kg.
Study burden and risks
Mortality and the risk of renal insufficiency after infection in patients with
liver cirrhosis is high. This outweighs the low risk of adverse effects due to
the administration of IV albumin at day 1 and 3 after infection. Moreover, the
safety of administration of IV albumin at day 1 and 3 in spontaneous bacterial
peritonitis has been clearly established in patients with cirrhosis and this is
routinely performed in daily practice in these patients.
Villarroel 170
Barcelona 08036
ES
Villarroel 170
Barcelona 08036
ES
Listed location countries
Age
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
- > 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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2013-002416-27-NL |
ClinicalTrials.gov | NCTnummer02034279 |
CCMO | NL50305.058.15 |