Albumin Administration in Cirrhotic Patients With Bacterial Infection and a Systemic Inflammatory Response Syndrome Unrelated to Spontaneous Bacterial Peritonitis (ALB-CIRINF)

Effects of Albumin Administration in Septic Cirrhotic Patients With Child > 8 Unrelated to Spontaneous Bacterial Peritonitis on Renal Function and Survival: A Multicenter Randomized Controlled Trial Comparing Use and Non-use of Human Albumin (Vialebex ®)

Patients with cirrhosis present an increased susceptibility to bacterial infections. Spontaneous bacterial peritonitis (SBP) is the most frequent infection and induces severe circulatory dysfunction associated with renal failure in about 30% of cases. Renal failure is a reliable surrogate marker of in-hospital mortality in patients with SBP or with non-SBP infections. Albumin, as an adjuvant to antibiotherapy reduces significantly the rate of renal failure, in-hospital mortality, and overall mortality (Sort P, et al. NEJM 1999). However, little is known regarding the effect of albumin administration in patients with non-SBP infections. Two recent prospective studies demonstrated that non-SBP infections are associated with impairment of the effective circulating volume and precipitate renal failure whatever the presence of ascites.

The aim of this randomized clinical trial is to evaluate the effects of albumin, associated with appropriate antibiotic therapy, on occurrence or deterioration of renal failure and survival in septic (SIRS criteria required) cirrhotic patients with non-SBP infections and presenting with a Child-Pugh score > 8.

Study Overview

• Status: Terminated
• Conditions: Sepsis; Renal Failure; Cirrhosis
• Intervention / Treatment: Drug: Human Albumin

Detailed Description

• Cirrhosis defined by clinical, laboratory or ultrasonographic findings
• Child-Pugh > 8
• Sepsis defined by the presence of proved or suspected infection with two of the four SIRS (systemic inflammatory response syndrome) criteria (Wong F, et al. Sepsis in cirrhosis: report on the 7th meeting of the international ascites club. Gut 2005)
• Creatinine < 160 µmol/L

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU
  • Angers, France, 49933
    • CHU
  • Belfort, France, 90016
    • CHBM
  • Besançon, France, 25000
    • Centre Hospitalier Universitaire de Besancon
  • Bondy, France, 93143
    • Hôpital Jean Verdier
  • Bordeaux, France, 33404
    • CHU
  • Brest, France, 29609
    • CHU
  • Caen, France, 14033
    • CHU
  • Clamart, France, 92141
    • Hopital Antoine Beclere
  • Clermont-Ferrand, France, 63003
    • Centre Hospitalier Universitaire
  • Clichy, France, 92110
    • Hopital Beaujon
  • Créteil, France, 94010
    • CHIC
  • Dijon, France, 21079
    • CHU
  • Dunkerque, France, 59385
    • Centre Hospitalier
  • Evry, France, 91014
    • CH Francilien
  • Gonesse, France, 95300
    • CH
  • Grenoble, France, 38043
    • CHU
  • Lens, France, 62307
    • CH
  • Lille, France, 59037
    • CHU
  • Marseille, France, 13354
    • Centre Hospitalier Universitaire
  • Maubeuge, France, 59607
    • Centre Hospitalier
  • Nancy, France, 54035
    • Centre Hospitalier Universitaire
  • Nice, France, 06003
    • CHU
  • Orléans, France, 45032
    • CHR
  • Paris, France
    • Hôpital Saint Antoine
  • Paris, France, 75020
    • CHU Tenon
  • Paris, France, 94010
    • Hopital Henri Mondor
  • Pau, France, 64046
    • CHU
  • Reims, France, 51092
    • CHU
  • Rouen, France, 76031
    • CHU
  • Saint Brieuc, France, 22027
    • CH
  • Toulouse, France, 31059
    • CHU
  • Tourcoing, France, 59208
    • CH
  • Tours, France, 37044
    • Centre hospitalier régional universitaire
  • Vesoul, France, 70014
    • Centre Hospitalier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cirrhosis defined by clinical, laboratory or ultrasonographic findings
• Child-Pugh > 8
• Sepsis defined by the presence of proved or suspected infection with two of the four SIRS (systemic inflammatory response syndrome) criteria (Wong F, et al. Sepsis in cirrhosis: report on the 7th meeting of the international ascites club. Gut 2005)
• Creatinine < 160 µmol/L
• Written informed consent
• Absence of the exclusion criteria

Exclusion Criteria:

• Spontaneous bacterial peritonitis
• Difficult to treat infections such as : endocarditis, septic arthritis, osteomyelitis
• Heart insufficiency (YHA III-IV)
• Digestive bleeding during the week preceding the study
• Septic shock
• Hepatocellular carcinoma : stage D
• Use of antibiotics during the week preceding the study, except noroxin used for long-term antibioprophylaxy
• Diseases which can influence the short term survival

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual treatment; intravenous injection of Human Albumin. 1,5g/kg on first day and 1g/kg on third day
Experimental: Human Albumin; 1,5g/kg on first day and 1g/kg on third day.	Drug: Human Albumin; Administration: 1,5 g/kg at Day 1 and 1g/kg at Day 3 In case of a new infection appears in the 3 months, the same doses will be administrated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal failure rate	Occurrence or deterioration of renal failure at 3 months	at 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
In-hospital and at 3-month mortality	during hospitalization and 3-month mortality

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Thierry Thevenot, PH, CHU de Besancon

Publications and helpful links

General Publications

• Thevenot 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 23, 2011
• First Submitted That Met QC Criteria: May 23, 2011
• First Posted (Estimate): May 25, 2011

Study Record Updates

• Last Update Posted (Estimate): May 13, 2014
• Last Update Submitted That Met QC Criteria: May 12, 2014
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis
• Other Study ID Numbers: N/2008/51