Albumin Administration in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis

NCT00124228 | Completed Phase 3

• 2 other identifiers: FIS05/0273FIS
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Spontaneous bacterial peritonitis (SBP) present in cirrhotic patients induces severe circulatory dysfunction, which results in renal failure in up to 30% of the patients. Renal failure is an important prognostic marker, representing the major predictive factor of in-hospital mortality. Recent studies have shown that plasma volume expansion with albumin associated with cefotaxime in patients with SBP is more efficient to prevent renal failure than cefotaxime treatment alone. The in-hospital and three-month mortality rates, furthermore, were significantly lower in the group treated with albumin. It is not known if other bacterial infections unrelated to SBP represent a risk factor for the development of renal failure among cirrhotic patients. The researcher's group has recently performed a study to evaluate the incidence, characteristics and outcome, of renal failure in patients with cirrhosis and bacterial infections unrelated to SBP associated with the systemic inflammatory response syndrome (Terra, unpublished results). Among a total of 106 patients, 29 (27%) presented renal failure during the course of infection. Renal failure was characterized by intense renal vasoconstriction (intrarenal resistive index of 0.83 +/- 0.09, measured by Doppler ultrasound), reduction of mean arterial pressure and an important activation of endogenous vasoconstriction systems. The three-month survival probability of patients with infection and renal failure was 34 %, much lower than that of patients with infection but not presenting renal failure (87%, p\<0.0001). These results suggest that the development of renal failure in patients with cirrhosis and bacterial infections different from SBP, associated with signs of a systemic inflammatory response, is very frequent and results in a very poor prognosis. Taken as a whole, these data strongly indicate the need to consider these patients as candidates for liver transplantation and to plan strategies for its prevention. The objective of this project, therefore, is to evaluate if the plasma volume expansion with albumin, associated with conventional antibiotic therapy, can prevent the development of renal failure and increase survival rates in cirrhotic patients with bacterial infections unrelated to spontaneous bacterial peritonitis.

Conditions

Cirrhosis

Keywords

Cirrhosis; Infection; Sepsis; Renal failure

Outcome Measures

Primary Outcomes (2)

• Renal failure rate

  presence of renal failure at admision or development during hospitalization

  During hospitalization

• Renal failure rate

  outcome of renal failure 3 months after inclusion in the study

  at 3 month

Secondary Outcomes (5)

• In-hospital and at 3 month mortality

  During hospitalization and 3-month mortality

• Evaluation of the treatment effects over the renal vascular territory

  at the end of antibiotic treatment (infection resolution)

• Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems

  At baseline, at day 3rd and at the end of treatment

• Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines

  At baseline, at day 3rd and at the end of treatment

• Evaluation of heart function and its relationship with the development of renal failure

  At baseline and at the end of treatment

Study Arms (2)

1

NO INTERVENTION

Antibiotic following hospital Protocols according the cause of the infection .

2

ACTIVE COMPARATOR

Antibiotic following hospital Protocols according the cause of infection plus albumin

Drug: Human Albumin

Interventions

Human Albumin DRUG

albumin 1.5g/kg body weight the first day of inclusion plus 1g/kg/body weight the 3th day of inclusion.

2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years;
• Cirrhosis defined by clinical, analytical or histological criteria;
• Active infection defined by the presence of at least two of the criteria for systemic inflammatory response syndrome (SIRS), necessarily including neutrophilia in the hemogram. In case of a positive culture, the presence of only one of the SIRS criteria is considered sufficient for the infection diagnosis. SIRS is defined by: temperature \>38º or \<36º C, heart beat \>90 beats/min, breath frequency \>20 resp/min, white cell count \>12000/mm3 or \<4000/mm3 or \>6% of immature cells.
• Written informed consent.

You may not qualify if:

• Use of antibiotics during the week preceding the study, except for prophylaxis of spontaneous bacterial peritonitis;
• Hepatocarcinoma: hepatocarcinoma patients presenting more than 3 nodes \> 3 cm, or one node larger than 5 cm, tumoral portal thrombosis or extrahepatic tumor extension;
• Heart insufficiency or advanced chronic obstructive pulmonary disease;
• Digestive bleeding during the week preceding the study;
• Presence of septic shock, defined as: sepsis with hypotension (systolic pressure \<90 mm Hg or a decrease \>40 mm Hg as compared to the basal pressure), in spite of an adequate liquid reposition, signs of a poor peripheral perfusion or need of vasoactive drugs;
• Plasma creatinine \> 3 mg/dL;
• Existence of diseases which can influence the short term survival.

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• Fondo de Investigacion Sanitaria: collaborator

Study Sites (1)

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Related Publications (1)

• 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.

  PMID: 22732511 DERIVED

MeSH Terms

Conditions

Fibrosis; Infections; Sepsis; Renal Insufficiency

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Systemic Inflammatory Response Syndrome; Inflammation; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Study Officials

• Pere Ginès, Dr

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 26, 2005
• First Posted: July 27, 2005
• Study Start: November 1, 2004
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: May 27, 2010

Record last verified: 2009-08

Locations

ES (1)