Low-dose Albumin Solution in SBP: a Randomized Double-blind Pilot Study (ALTERNATE)
Effect of Intravenous Albumin (Standard vs Dose Reduced Regimen) On Renal Impairment and Mortality in Patients With Cirrhosis and Spontaneous Bacterial Peritonitis: A Double Blind Randomized Clinical Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with cirrhosis who had spontaneous bacterial peritonitis (SBP) and who are admitted from March 2006 to a single university hospital were evaluated for inclusion in the study. The study was approved by the investigational review boar, and patients gave written informed consent to participate. Inclusion criteria were a cytological diagnosis of SBP, in the absence of findings suggestive of secondary peritonitis; age between 18 and 80 years; no antibiotic treatment within one week before the diagnosis of spontaneous bacterial peritonitis (except for prophylactic treatment with norfloxacin or trimethoprim/sulfamethoxazole); the absence of other infections, shock, gastrointestinal bleeding, grade 3 or 4 hepatic encephalopathy, cardiac failure, and any disease (e.g., advanced neoplasia) that could affect the short term prognosis; a serum creatinine level of no more than 3 mg per deciliter 265 µmol per liter); and the absence of potential causes of dehydration (such as diarrhea or an intense response to diuretic treatment) within one week before the diagnosis of peritonitis.
Patients were randomly assigned to one of two groups: standard regimen (SR) vs dose reduced regimen (DRR). Randomization was performed independently with the use of sealed envelopes containing the treatment assignments, which were based on random numbers generated by computer. All the investigators were unaware of the treatment assignments.
Physical examination and routine laboratory tests (blood-cell counts and liver and renal tests) and measurement of plasma rennin activity were performed on day 1 of therapy in all patients. Laboratory measurements were repeated every three days until discharge. Rennin activity was repeated on day 7. Intravenous cefotaxime was given daily in doses that varied accordingly to creatinine. Albumin was given at a dose of 1.5 or 1 g per kilogram of body weight on day 1, followed by 1 or 0.5 g per kilogram on day 3 (SR vs DRR). Albumin was diluted in saline solution until total volume of 1000 ml on day 1 and 500 ml on day 3. Albumin was prepared in a bottle with same color, volume and aspect in both groups. Diuretic treatment was not give until day 5 of treatment and therapeutic paracentesis > 3 liters was not allowed until the infection had resolved. Response to cefotaxime was considered when the polymorphonuclear-cell count in ascitic fluid reduced by at least 50%. Antibiotic treatment was modified when no response to cefotaxim occurred according to the in vitro susceptibility of the isolated organism or was modified empirically in patients with negative blood and ascitic-fluid cultures. Prophylactic norfloxacin or trimethoprim/sulfamethoxazole therapy was initiated after the resolution of infection and was maintained throughout the follow-up period. Renal failure at the time of enrollment was diagnosed when the serum creatinine level was more than 1.5 mg per deciliter. Renal impairment was defined as a nonreversible deterioration of renal function during hospitalization. In patients without renal failure at enrollment, renal impairment was diagnosed when serum creatinine level increased by more than 50 percent of the pretreatment value, to level higher than 1.5 mg per deciliter. In patients with preexisting renal failure, an increase in serum creatinine level by more than 50 percent from base line was required for a diagnosis of renal impairment. After the resolution of infection, patients with tense ascites were treated with total paracentesis and the administration of albumin, regardless of treatment assignment, followed by sodium restriction and diuretic therapy, and those with moderate ascites were treated only with sodium restriction and diuretics. After discharge from the hospital, patients were followed until 90 days after enrollment.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
Rio Grande do Sul
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Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
- Hospital de Clinicas de Porto Alegre
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- cytological diagnosis of spontaneous bacterial peritonitis
- age between 18 and 80 years
- written informed consent
Exclusion Criteria:
- findings suggestive of secondary peritonitis
- antibiotic treatment within one week before the diagnosis of spontaneous bacterial peritonitis (except for prophylactic treatment with norfloxacin or trimethoprim/sulfamethoxazole)
- other infections, shock, gastrointestinal bleeding, grade 3 or 4 hepatic encephalopathy, cardiac failure, and any disease (e.g., advanced neoplasia) that could affect the short term prognosis
- creatinine level of more than 3 mg per deciliter
- potential causes of dehydration (such as diarrhea or an intense response to diuretic treatment) within one week before the diagnosis of peritonitis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Standard regimen
Albumin in standard regimen (1.5 g/Kg IV on day 1 and 1 g/kg IV on day 3)with saline solution to complete total volume of 1000 ml on day 1 and 500 ml on day 3
|
1.5 g/kg IV on day 1 and 1 g/kg IV on day 3 with saline solution to complete total volume of 1000 ml on day 1 and 500 ml on day 3. Infusion in 4 hours.
Other Names:
1 g/kg IV on day 1 and 0.5 g/kg IV on day 3 with saline solution to complete total volume of 1000 ml on day 1 and 500 ml on day 3. Infusion in 4 hours.
Other Names:
|
|
Experimental: Dose reduced regimen
Albumin in dose reduced regimen (1 g/kg IV on day 1 and 0.5 g/kg IV on day 3) with saline solution to complete total volume of 1000 ml on day 1 and 500 ml on day 3
|
1.5 g/kg IV on day 1 and 1 g/kg IV on day 3 with saline solution to complete total volume of 1000 ml on day 1 and 500 ml on day 3. Infusion in 4 hours.
Other Names:
1 g/kg IV on day 1 and 0.5 g/kg IV on day 3 with saline solution to complete total volume of 1000 ml on day 1 and 500 ml on day 3. Infusion in 4 hours.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
renal impairment
Time Frame: within first 90 days
|
within first 90 days
|
|
all cause mortality
Time Frame: within first 90 days
|
within first 90 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Plasmatic renin activity
Time Frame: day 0 and 7
|
day 0 and 7
|
Collaborators and Investigators
Investigators
- Principal Investigator: Mário R Álvares-da-Silva, Hospital de Clinicas de Porto Alegre
- Study Chair: Alexandre Araujo, Hospital de Clinicas de Porto Alegre
- Study Chair: Gabriela Rossi, Hospital de Clinicas de Porto Alegre
- Study Chair: Antônio B Lopes, Hospital de Clinicas de Porto Alegre
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 05-352
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