Advanced Chronic Liver DiseasePhase 4INFECIR2NCT02034279
The INFECIR-2 Albumin Prevention Study
A Phase 4 study testing Albumin in people with Advanced Chronic Liver Disease and Urinary Infection, run by EASL - CLIF Consortium at 1 site in Spain.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Chronic Liver Disease, Urinary Infection, Pneumonia
- What is being tested?
- Albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 1 siteSpain
- Study dates
- May 2014to 10 Feb 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- > 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
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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).
Read the detailed 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.
- Conditions
- Advanced Chronic Liver Disease, Urinary Infection, Pneumonia, Cholangitis, Other Bacterial Diseases
- Being tested
- Albumin
- Keywords
- cirrhosis
- Medical subject headings
- Urinary Tract Infections, Pneumonia, Cholangitis, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlbuminDrug
Also called Albutein 20 by Grifols
Intravenous infusion of 20% albumin
| Study group | Role | What they receive |
|---|---|---|
| Intravenous infusion of albumin | Experimental | Treatment arm will receive intravenous albumin on days 1 and 3 plus antibiotics Receives: Drug: Albumin |
| No albumin | No intervention | Only antibiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
survival
Hospital survival will be the primary outcome
Measured: hospitalization
Secondary outcomes (5)
survival
Percentage of subjects within each arm that survived at these time points
Measured: 28-d and 90-day survival
Renal dysfunction
number of participants
Measured: hospitalization (expected average 2 weeks)
circulatory dysfunction
plasma concentration of hormones
Measured: day 3 and day of infection resolution
Inflammation and endothelial function
Plasma concentration of cytokines
Measured: day of infection resolution
subsequent organ failure
number of organ failures
Measured: hospitalization (expected average 2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2014 (estimated)
- Study startMay 2014
- Primary completion31 Dec 2016
- Study completion10 Feb 2017
Why it stopped: Low recruitment rate and expiration of the study drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Advanced Chronic Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- EASL - CLIF Consortium
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thierry Gustot, Principal investigator, Erasme University Hospital, Brussels, BelgiumFrederick Nevens, Principal investigator, University Hospitals KU, Leuven, BelgiumFaouzi Saliba, Principal investigator, Hôpital Paul Brousse, Villejuif, FranceFrançois Durand, Principal investigator, Hôpital Beaujon, Clichy, FranceMatthias Dollinger, Principal investigator, University of Ulm, Heidelberg and Tübingen, GermanyStefan Zeuzem, Principal investigator, University Hospital of Frankfurt, GermanyAlexander Gerbes, Principal investigator, University Hospital of Munich, GermanyJonel Trebicka, Principal investigator, University Hospital of Bonn, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02034279
- Sponsor's protocol ID
- INFECIR 2
- Other IDs
- 2013-002416-27
- Acronym
- INFECIR2
- Status last verified
- May 2017
- First submitted
- 7 Jan 2014
- Last updated
- 18 May 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Undecided yet
Publications
Guevara M, Terra C, Nazar A, Sola E, Fernandez J, Pavesi M, Arroyo V, Gines 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.
PubMed 22732511Thevenot T, Bureau C, Oberti F, Anty R, Louvet A, Plessier A, Rudler M, Heurgue-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.
PubMed 25463545Fernandez J, Angeli P, Trebicka J, Merli M, Gustot T, Alessandria C, Aagaard NK, de Gottardi A, Welzel TM, Gerbes A, Soriano G, Vargas V, Albillos A, Salerno F, Durand F, Banares R, Stauber R, Prado V, Arteaga M, Hernandez-Tejero M, Aziz F, Morando F, Jansen C, Lattanzi B, Moreno C, Campion D, Gronbaek H, Garcia R, Sanchez C, Garcia E, Amoros A, Pavesi M, Claria J, Moreau R, Arroyo V. Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. Clin Gastroenterol Hepatol. 2020 Apr;18(4):963-973.e14. doi: 10.1016/j.cgh.2019.07.055. Epub 2019 Aug 5.
PubMed 31394283
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02034279
- Acronym / sponsor ID
- INFECIR2 / INFECIR 2
- Conditions
- Advanced Chronic Liver Disease, Urinary Infection, Pneumonia, Cholangitis, Other Bacterial Diseases
- Keywords
- cirrhosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment rate and expiration of the study drug
- Enrolment
- 136 participants (actual)
- Lead sponsor
- EASL - CLIF ConsortiumUniversity, hospital or other
- Study start
- May 2014 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 10 Feb 2017 (actual)
- First posted
- 13 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous infusion of albumin | Experimental | Drug: AlbuminTreatment arm will receive intravenous albumin on days 1 and 3 plus antibiotics |
| No albumin | No intervention | –Only antibiotics |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (21 listed)
- > 72h after infection diagnosis
- Pregnancy
- Acute or subacute liver failure without underlying cirrhosis
- Septic shock
- Severe acute respiratory distress syndrome (Pa02/Fi02 ≤ 100)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlbuminAlso: Albutein 20 by GrifolsIntravenous infusion of 20% albumin | Drug | Intravenous infusion of albumin |
Primary outcome
survival
Time frame: hospitalization
Hospital survival will be the primary outcome
5 secondary outcomes
survival
Time frame: 28-d and 90-day survival
Renal dysfunction
Time frame: hospitalization (expected average 2 weeks)
circulatory dysfunction
Time frame: day 3 and day of infection resolution
Inflammation and endothelial function
Time frame: day of infection resolution
subsequent organ failure
Time frame: hospitalization (expected average 2 weeks)
Results and safety
The study was stopped early (reason given: Low recruitment rate and expiration of the study drug). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2017.
- Background: PubMed 22732511Guevara M, Terra C, Nazar A, Sola E, Fernandez J, Pavesi M, Arroyo V, Gines 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.
- Background: PubMed 25463545Thevenot T, Bureau C, Oberti F, Anty R, Louvet A, Plessier A, Rudler M, Heurgue-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.
- Derived from this study: PubMed 31394283Fernandez J, Angeli P, Trebicka J, Merli M, Gustot T, Alessandria C, Aagaard NK, de Gottardi A, Welzel TM, Gerbes A, Soriano G, Vargas V, Albillos A, Salerno F, Durand F, Banares R, Stauber R, Prado V, Arteaga M, Hernandez-Tejero M, Aziz F, Morando F, Jansen C, Lattanzi B, Moreno C, Campion D, Gronbaek H, Garcia R, Sanchez C, Garcia E, Amoros A, Pavesi M, Claria J, Moreau R, Arroyo V. Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. Clin Gastroenterol Hepatol. 2020 Apr;18(4):963-973.e14. doi: 10.1016/j.cgh.2019.07.055. Epub 2019 Aug 5.
- Web page of the INFECIR-2 RCTLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Undecided yet
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thierry Gustot principal investigator
Erasme University Hospital, Brussels, Belgium
Frederick Nevens principal investigator
University Hospitals KU, Leuven, Belgium
Faouzi Saliba principal investigator
Hôpital Paul Brousse, Villejuif, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Albumin in people with Advanced Chronic Liver Disease and Urinary Infection, run by EASL - CLIF Consortium at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment rate and expiration of the study drug). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
survival (time frame: hospitalization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02034279, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2017.