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

Primary Purpose

Cirrhosis

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Human Albumin
Sponsored by
Hospital Clinic of Barcelona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cirrhosis focused on measuring Cirrhosis, Infection, Sepsis, Renal failure

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Absence of the exclusion criteria described below Exclusion Criteria: 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; Severe dehydration (defined by a central venous pressure < 3 cm H2O due to severe diarrhea or to a strong response to diuretic treatment) at inclusion in the study; the patients with PVC lower than 3 will receive plasma volume expansion with saline and will be reevaluated within 24 h. If the expansion is able to correct PVC (defined as PVC > 3), the patients will be apt to be included in the study. Existence of diseases which can influence the short term survival.

Sites / Locations

  • Hospital Clínic de Barcelona

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

1

2

Arm Description

Antibiotic following hospital Protocols according the cause of the infection .

Antibiotic following hospital Protocols according the cause of infection plus albumin

Outcomes

Primary Outcome Measures

Renal failure rate
presence of renal failure at admision or development during hospitalization
Renal failure rate
outcome of renal failure 3 months after inclusion in the study

Secondary Outcome Measures

In-hospital and at 3 month mortality
Evaluation of the treatment effects over the renal vascular territory
Renal resistence index will be determined at baseline and at the end of treatment
Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems
Evaluation of vasoactive systems and the development or presence of renal failure. These relationships will be evaluated at baseline, at day 3rd and at the end of antibiotic treatment
Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines
Evaluation of cytokines levels and the development or presence of renal failure. These relationships will be evaluated at baseline, at day 3rd and at the end of antibiotic treatment
Evaluation of heart function and its relationship with the development of renal failure
Evaluation of heart function and the development or presence of renal failure. These relationships will be evaluated at baseline, and at the end of antibiotic treatment

Full Information

First Posted
July 26, 2005
Last Updated
May 26, 2010
Sponsor
Hospital Clinic of Barcelona
Collaborators
Fondo de Investigacion Sanitaria
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1. Study Identification

Unique Protocol Identification Number
NCT00124228
Brief Title
Albumin Administration in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis
Acronym
Infecir
Official Title
Effects of Intravenous Albumin Administration on Renal Function and Survival in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis. A Prospective, Stratified, Randomized and Controlled Study.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Completed
Study Start Date
November 2004 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Hospital Clinic of Barcelona
Collaborators
Fondo de Investigacion Sanitaria

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Recent studies have shown that the administration of cefotaxime (first choice treatment for SBP) associated with plasma volume expansion with albumin in patients with SBP, was more efficient to prevent renal failure than cefotaxime treatment alone (10% vs. 33%, respectively). The in-hospital and three-month mortality rates, furthermore, were significantly lower in the group treated with albumin (10% vs. 29% and 22% vs. 41%, respectively). There was a significant increase in the plasma renin activity in the group treated with cefotaxime alone as compared to the group receiving cefotaxime associated with the expansion with albumin. A direct relationship between plasma renin activity levels and the development of renal failure was also observed. Based on the previous information the main objective of this study is to evaluate if the plasma volume expansion with albumin associated to conventional antibiotics therapy, can prevent the development of renal failure and increase survival rates in cirrhotic patients with bacterial infections unrelated to spontaneous bacterial peritonitis. If that proves to be the case, albumin should be administered as first choice treatment associated with antibiotics to all the cirrhotic patients with bacterial infection and systemic inflammatory response syndrome. Other parameters to be investigated include: In-hospital mortality. Evaluation of the treatment effects over the renal vascular territory, estimated by Doppler ultrasonography of the intrarenal arteries. Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems: plasma renin activity, plasma concentration of aldosterone, noradrenaline, atrial natriuretic factor and nitrites. Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines: tumor necrosis factor-α, interleukin-6, interleukin-1, interleukin-10. Evaluation of heart function and its relationship with the development of renal failure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis
Keywords
Cirrhosis, Infection, Sepsis, Renal failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
No Intervention
Arm Description
Antibiotic following hospital Protocols according the cause of the infection .
Arm Title
2
Arm Type
Active Comparator
Arm Description
Antibiotic following hospital Protocols according the cause of infection plus albumin
Intervention Type
Drug
Intervention Name(s)
Human Albumin
Intervention Description
albumin 1.5g/kg body weight the first day of inclusion plus 1g/kg/body weight the 3th day of inclusion.
Primary Outcome Measure Information:
Title
Renal failure rate
Description
presence of renal failure at admision or development during hospitalization
Time Frame
During hospitalization
Title
Renal failure rate
Description
outcome of renal failure 3 months after inclusion in the study
Time Frame
at 3 month
Secondary Outcome Measure Information:
Title
In-hospital and at 3 month mortality
Time Frame
During hospitalization and 3-month mortality
Title
Evaluation of the treatment effects over the renal vascular territory
Description
Renal resistence index will be determined at baseline and at the end of treatment
Time Frame
at the end of antibiotic treatment (infection resolution)
Title
Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems
Description
Evaluation of vasoactive systems and the development or presence of renal failure. These relationships will be evaluated at baseline, at day 3rd and at the end of antibiotic treatment
Time Frame
At baseline, at day 3rd and at the end of treatment
Title
Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines
Description
Evaluation of cytokines levels and the development or presence of renal failure. These relationships will be evaluated at baseline, at day 3rd and at the end of antibiotic treatment
Time Frame
At baseline, at day 3rd and at the end of treatment
Title
Evaluation of heart function and its relationship with the development of renal failure
Description
Evaluation of heart function and the development or presence of renal failure. These relationships will be evaluated at baseline, and at the end of antibiotic treatment
Time Frame
At baseline and at the end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Absence of the exclusion criteria described below Exclusion Criteria: 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; Severe dehydration (defined by a central venous pressure < 3 cm H2O due to severe diarrhea or to a strong response to diuretic treatment) at inclusion in the study; the patients with PVC lower than 3 will receive plasma volume expansion with saline and will be reevaluated within 24 h. If the expansion is able to correct PVC (defined as PVC > 3), the patients will be apt to be included in the study. Existence of diseases which can influence the short term survival.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pere Ginès, Dr
Organizational Affiliation
Hospital Clinic of Barcelona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Clínic de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
22732511
Citation
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.
Results Reference
derived

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

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