Albumin Administration in Patients With Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis
Information source: Hospital Clinic of Barcelona
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cirrhosis
Intervention: Human Albumin (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Hospital Clinic of Barcelona Official(s) and/or principal investigator(s): Pere Ginès, Dr, Principal Investigator, Affiliation: Hospital Clínic de Barcelona
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the systemic inflammatory response syndrome (Terra, unpublished results).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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Renal failure rateRenal failure rate
Secondary outcome: In-hospital and at 3 month mortalityEvaluation of the treatment effects over the renal vascular territory Evaluation of the relationship between the development of renal failure and the activity of endogenous vasoactive systems Evaluation of the relationship between the development of renal failure and the concentration of inflammatory cytokines Evaluation of heart function and its relationship with the development of renal failure
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
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.
Locations and Contacts
Hospital Clínic de Barcelona, Barcelona 08036, Spain
Additional Information
Starting date: November 2004
Last updated: May 26, 2010
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