Randomized Comparison of Two Albumin Administration Schedules for Spontaneous Bacterial Peritonitis (SBP)

NCT ID: NCT00761098

Last Updated: 2011-01-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2010-08-31

Brief Summary

Spontaneous bacterial peritonitis (SBP) is a common and frequently fatal complication of end-stage liver disease with a mortality of up to 10%, primarily due to the development of kidney failure. Current standard practice is to treat this infection with broad spectrum antibiotics and salt-poor albumin administration on day one and three of treatment. In this study the investigators test the hypothesis that the administration of a second dose of albumin at 48 hours only to patients with renal insufficiency, is as effective at preventing kidney failure as administering the second dose to all patients at 72 hours.

Detailed Description

Spontaneous bacterial peritonitis (SBP), infection of the peritoneal fluid(ascites) without evidence of a surgically treatable source, is a common and frequently fatal complication of patients with endstage hepatic cirrhosis. It originates with the passage of bacteria from the intestinal lumen to the systemic circulation and then to the ascitic fluid. Early diagnosis with paracentesis (aspiration of an ascites fluid sample to assess for evidence of infection) and the development of nonnephrotoxic third generation cephalosporin antibiotics have decreased the in hospital mortality from nearly 100% to approximately 30%. Mortality in patients with SBP is invariably associated with the development of functional renal failure. Recently, the administration of two large doses of human serum albumin at diagnosis and at 72 hours has been reported to further reduce mortality and renal failure to 10%. These findings have lead to the recommendation that patients with SBP be treated with albumin. However, no study has evaluated the necessary amount and timing of albumin administration required for its beneficial action.

In this study we test the hypothesis that the administration of a second dose of albumin at 48 hours only to patients with renal insufficiency, is as effective at preventing kidney failure as administering the second dose to all patients at 72 hours.

80 consecutive patients with cirrhosis and SBP who are at risk for renal failure will be enrolled at either the Columbia University Medical Center or The New York Hospital Weill Cornell Medical Center. Baseline clinical and biochemical data will be obtained for etiology and severity of liver disease. All patients will receive antibiotics and salt poor albumin at 1.5g/kg at time of diagnosis and diuretics discontinued (current standard of care). Patients will be randomized to receive the second dose (1.0 gm/kg) at 72 hours (group 1, standard of care) or at 48 hours only if renal function remains elevated after two days of therapy (Group 2). For the latter group of patients, albumin will be administered if the Cr is > 1.0 mg/dl or if the BUN or creatinine levels are higher than admission levels at 48 hours. If albumin is not administered at 48 hours, renal function will be monitored daily, and it will be administered should the BUN or creatinine increase to levels greater than those on admission. Renal failure rates, duration of transient azotemia, mortality, and albumin utilization rated will be compared between the groups who receive albumin in the usual manner at 72 hours versus those who receive it at 48 hours based on renal function.

Conditions

Spontaneous Bacterial Peritonitis; Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Standard Care (albumin administered day 1 (1.5g/kg) and day 3 (1.0g/kg)

Group Type: ACTIVE_COMPARATOR

Standard Care

Intervention Type: DRUG

Standard Care: 25% salt poor albumin administered day 1 (1.5g/kg) and day 3 (1.0g/kg)

2

Albumin administered per standard care on day 1 (1.5g/kg). Second dose administered on day 2 only to those individuals with renal insufficiency and risk for renal failure.

Group Type: EXPERIMENTAL

Experimental

Intervention Type: DRUG

25% Salt Poor Albumin administered per standard care on day 1 (1.5g/kg). Second dose administered on day 2 only to those individuals with renal insufficiency and risk for renal failure.

Interventions

Standard Care

Standard Care: 25% salt poor albumin administered day 1 (1.5g/kg) and day 3 (1.0g/kg)

Intervention Type: DRUG

Experimental

25% Salt Poor Albumin administered per standard care on day 1 (1.5g/kg). Second dose administered on day 2 only to those individuals with renal insufficiency and risk for renal failure.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18 to 75
• End Stage Liver Disease / Cirrhosis
• Documented SBP (ANC > 250 or positive ascites culture)
• Ability to provide informed consent
• Serum Creatinine > 1.0 and/or Total Bilirubin > 4.0

Exclusion Criteria

• Nonportal hypertensive ascites (i.e. malignancy)
• Hepatic Encephalopathy precluding informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Weill Cornell Medical Center / Columbia Prebyterian Medical Center

Principal Investigators

Samuel H Sigal, MD

Role: PRINCIPAL_INVESTIGATOR

New York Presbyterian Hospital - Cornell/Columbia

Ilan S Weisberg, MD

Role: STUDY_DIRECTOR

New York Presbyterian Hospital - Cornell/Columbia

Locations

New York Presbyterian Hospital - Weill Cornell Medical Center

New York, New York, United States

Site Status: RECRUITING

New York Presbyterian Hospital - Columbia University Medical Center

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Samuel H Sigal, MD

Role: CONTACT

shs2015@med.cornell.edu

646-962-5483

Ilan S Weisberg, MD

Role: CONTACT

iw2104@columbia.edu

646-962-4800

Facility Contacts

Samuel H Sigal, MD

Role: primary

shs2015@med.cornell.edu

646-962-5483

Ilan S Weisberg, MD

Role: backup

iw2104@columbia.edu

646-962-4800

Samuel H Sigal, MD

Role: primary

shs2015@med.cornell.edu

212-305-9140

Ilan S Weisberg, MD

Role: backup

iw2104@columbia.edu

212-305-9140

References

Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, Castells L, Vargas V, Soriano G, Guevara M, Gines P, Rodes J. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999 Aug 5;341(6):403-9. doi: 10.1056/NEJM199908053410603.

Reference Type: BACKGROUND

PMID: 10432325 (View on PubMed)

Other Identifiers

#0410007526/1104-564

Identifier Type: -

Identifier Source: org_study_id