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

• ClinicalTrials.gov Identifier: NCT00124228
• Recruitment Status: Completed
• First Posted: July 27, 2005
• Last Update Posted: May 27, 2010
• Sponsor: Hospital Clinic of Barcelona
• Collaborator: Fondo de Investigacion Sanitaria
• Information provided by: Hospital Clinic of Barcelona

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cirrhosis and bacterial infections unrelated to SBP associated with the systemic inflammatory response syndrome (Terra, unpublished results).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.

Condition or disease	Intervention/treatment	Phase
Cirrhosis	Drug: Human Albumin	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: November 2004
• Actual Primary Completion Date: October 2008
• Actual Study Completion Date: October 2008

Arms and Interventions

Arm	Intervention/treatment
No Intervention: 1; Antibiotic following hospital Protocols according the cause of the infection .
Active Comparator: 2; Antibiotic following hospital Protocols according the cause of infection plus albumin	Drug: Human Albumin; albumin 1.5g/kg body weight the first day of inclusion plus 1g/kg/body weight the 3th day of inclusion.

Outcome Measures

Primary Outcome Measures :

1. Renal failure rate [ Time Frame: During hospitalization ]
   presence of renal failure at admision or development during hospitalization
2. Renal failure rate [ Time Frame: at 3 month ]
   outcome of renal failure 3 months after inclusion in the study

Secondary Outcome Measures :

1. In-hospital and at 3 month mortality [ Time Frame: During hospitalization and 3-month mortality ]
2. Evaluation of the treatment effects over the renal vascular territory [ Time Frame: at the end of antibiotic treatment (infection resolution) ]
   Renal resistence index will be determined at baseline and at the end of treatment
3. Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems [ Time Frame: At baseline, at day 3rd and at the end of treatment ]
   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
4. Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines [ Time Frame: At baseline, at day 3rd and at the end of treatment ]
   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
5. Evaluation of heart function and its relationship with the development of renal failure [ Time Frame: At baseline and at the end of treatment ]
   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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

Spain

Hospital Clínic de Barcelona

Barcelona, Spain, 08036

Sponsors and Collaborators

Hospital Clinic of Barcelona

Fondo de Investigacion Sanitaria

Investigators

• Principal Investigator: Pere Ginès, Dr; Hospital Clinic of Barcelona

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Fondo Investigación Sanitaria España, 05/0273
• ClinicalTrials.gov Identifier: NCT00124228
• Other Study ID Numbers: FIS05/0273; FIS
• First Posted: July 27, 2005
• Last Update Posted: May 27, 2010
• Last Verified: August 2009

Keywords provided by Hospital Clinic of Barcelona:

Cirrhosis; Infection; Sepsis; Renal failure

Additional relevant MeSH terms:

Infections; Peritonitis; Liver Cirrhosis; Fibrosis; Pathologic Processes; Liver Diseases; Digestive System Diseases; Intraabdominal Infections; Peritoneal Diseases