Albumin Administration in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis
Condition: Cirrhosis
MeSH terms: Infections; Peritonitis; Liver Cirrhosis; Fibrosis
Study type: Interventional
Phase: Phase 3

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      the systemic inflammatory response syndrome (Terra, unpublished results).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.
    

Intervention name(s): Human Albumin
Intervention type(s): Drug
Intervention description(s): albumin 1.5g/kg body weight the first day of inclusion plus 1g/kg/body weight the 3th day of inclusion.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Cirrhosis; Infection; Sepsis; Renal failure