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

A Randomized Comparison of Two Albumin Administration Schedules for Spontaneous Bacterial Peritonitis

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.

Study Overview

• Status: Unknown
• Conditions: Cirrhosis; Spontaneous Bacterial Peritonitis
• Intervention / Treatment: Drug: Standard Care; Drug: Experimental

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • New York Presbyterian Hospital - Weill Cornell Medical Center
      • Contact: Samuel H Sigal, MD; Phone Number: 646-962-5483; Email: shs2015@med.cornell.edu
      • Contact: Ilan S Weisberg, MD; Phone Number: 646-962-4800; Email: iw2104@columbia.edu
      • Principal Investigator: Samuel H Sigal, MD
      • Sub-Investigator: Ilan S Weisberg, MD
      • Sub-Investigator: Arun Jesudian, MD
    • New York, New York, United States, 10032
      • Recruiting
      • New York Presbyterian Hospital - Columbia University Medical Center
      • Principal Investigator: Samuel H Sigal, MD
      • Sub-Investigator: Ilan S Weisberg, MD
      • Contact: Samuel H Sigal, MD; Phone Number: 212-305-9140; Email: shs2015@med.cornell.edu
      • Contact: Ilan S Weisberg, MD; Phone Number: 212-305-9140; Email: iw2104@columbia.edu
      • Sub-Investigator: Reem Sharaiha, MD
      • Sub-Investigator: Brian Kim, MD
      • Sub-Investigator: Robert Brown, MD, MPH
      • Sub-Investigator: Lorna Dove, MD, MPH
      • Sub-Investigator: Scott Fink, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Standard Care (albumin administered day 1 (1.5g/kg) and day 3 (1.0g/kg)	Drug: Standard Care; Standard Care: 25% salt poor albumin administered day 1 (1.5g/kg) and day 3 (1.0g/kg)
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Renal Failure	Duration of Hospital Admission

Secondary Outcome Measures

Outcome Measure	Time Frame
All Cause Mortality	Duration of Hospital Admission
Albumin Utilization	Duration of Hospital Admission

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Samuel H Sigal, MD, New York Presbyterian Hospital - Cornell/Columbia; Study Director: Ilan S Weisberg, MD, New York Presbyterian Hospital - Cornell/Columbia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Anticipated): May 1, 2010
• Study Completion (Anticipated): August 1, 2010

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 26, 2008
• First Posted (Estimate): September 29, 2008

Study Record Updates

• Last Update Posted (Estimate): January 4, 2011
• Last Update Submitted That Met QC Criteria: January 3, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: Cirrhosis; SBP
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Peritoneal Diseases; Intraabdominal Infections; Fibrosis; Peritonitis
• Other Study ID Numbers: #0410007526/1104-564