Role of Probiotics in the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Randomized Placebo Control Trial

May 14, 2008 updated by: All India Institute of Medical Sciences, New Delhi

Cirrhotic patients are predisposed to bacterial infection. A large proportion of which is spontaneous bacterial peritonitis(SBP), which are mainly caused by enteric bacteria.SBP in a cirrhotic patients is associated with a high mortality rate in the order of 30-80% per year.It has been demonstrated that cirrhotics who have an ascitic fluid protein concentration less than 1gm% are most susceptible to develop SBP by virtue of having low opsonising activity of ascitic fluid.Patients with liver cirrhosis have significant degrees of imbalance of intestinal flora.Translocation of intestinal bacteria being the major mechanism for the production of SBP.

Long-term antibiotic (norfloxacin) is very effective in preventing SBP caused by gram negative bacteria.But the problem with the long-term antibiotic prophylaxis is the potential for the development of infection with antibiotic-resistant bacteria.Further, quinolones have no effect on gram positive bacteria which is becoming one of the important cause of SBP.

Such experiences necessitate the need for strategies, other than antibiotic, to prevent intestinal bacterial overgrowth, bacterial translocation and SBP in patients with cirrhosis.Probiotics have been used successfully to alter the gut flora in many clinical conditions where growth and localization of non pathogenic bacteria replaces the pathogenic bacteria in the intestine.The probiotic bacteria, among which the most common are the lactose fermenting Lactobacilli, inhibit the growth of pathogenic bacteria by acidifying the gut lumen, competing for nutrients, and by producing antimicrobial substances. They adhere to the gut mucosa and by that are thought to prevent bacterial translocation from the gut.

The purpose of this study is to determine the effectiveness of probiotics in the prevention of spontaneous bacterial peritonitis in patients with cirrhosis with low protein ascites and those already have developed an episode SBP.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

AIMS :

To study the effect of a Probiotics administration in reducing the incidence of first episode of SBP among cirrhotics who have low protein(<1 gm/dl) ascites.

To study the effect of a Probiotics administration in reducing the incidence of second episode of SBP among cirrhotic who have already developed at least one episode of SBP.

Study design : Prospective randomized placebo control efficacy study.

Inclusion criteria: All patients with liver cirrhosis with ascites having either history of prior SBP or ascitic fluid protein <1 gm/dl will be included in the study irrespective of etiology.

Exclusion criteria :

  • Patients chronically treated with antibiotics or lactulose during past 30 days.
  • Patients having risk factor of small intestinal bacterial overgrowth other than cirrhosis - diabetes mellitus, history of abdominal surgery, immunomodulator drugs. Alcoholic cirrhotics who continue to take alcohol.
  • Patients with active or recent G.I. bleed (within prior 7 days).
  • Patients with advanced HCC, renal failure and portal vein thrombosis

Patients in primary prophylaxis group will be randomly allocated to receive either a Probiotics or placebo. While patients in secondary prophylaxis group will be randomized between Probiotics and norfloxacin.

The Probiotics used in this study will be VSL#3. The control will be given similar looking capsules containing galactose powder.It will be used in the form of capsules. A total dose of 450 billions CFU will be used. Norfloxacin will also be used as similar looking capsules. The drugs and placebo will be given for one year or till the end points of the study as mentioned below.

Monitoring Each patients will be tested for SBP( Ascitic fluid cell count as well as culture) at the interval of every 6 weeks till the end point of the study.The effect of Probiotics on gut flora will be assessed objectively by jejunal fluid culture analysis baseline at 6 months and 1 year of the start of the treatment. This will be done on some of the representative sample from both the groups. Development of an episode of SBP, hepatic encephalopathy and variceal bleeding will be noted.All patients will be prospectively followed up from the date of enrollment to see the primary outcome that is development of SBP. The secondary outcome of the study will be the development of encephalopathy, variceal bleeding ,renal failure and death of the patients.

End Points :

  1. completion of one year.
  2. development of an episode of SBP.
  3. Death.

Study Type

Interventional

Enrollment (Anticipated)

250

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Delhi
      • New Delhi, Delhi, India, 110029
        • Recruiting
        • All India Institute of Medical Sciences
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Ramesh Kumar, MD
        • Sub-Investigator:
          • Geeta Satapathy, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All patients with liver cirrhosis with ascites having either history of prior SBP or ascitic fluid protein <1 gm/dl will be included in the study irrespective of etiology.

Exclusion Criteria:

  • Patients chronically treated with antibiotics(that disturb/alter normal gut flora) or lactulose during past 30 days.
  • Patients having risk factor of small intestinal bacterial overgrowth other than cirrhosis - diabetes mellitus, history of abdominal surgery, immunomodulator drugs. Alcoholic cirrhotics who continue to take alcohol.
  • Patients with active or recent G.I. bleed (within prior 7 days).
  • Patients with advanced HCC, renal failure and portal vein thrombosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1, Primary prophylaxis

Patients with liver cirrhosis with ascites having ascitic fluid protein <1 gm/dl will be included in this arm.

They will be randomized between probiotics and placebo.
Drug: Probiotics and Placebo
The Probiotics used in this study will be VSL#3. The control will be given similar looking capsules containing galactose powder. It will be used in the form of capsules. A total dose of 450 billions CFU will be used. Norfloxacin, 400 mg /day, will also be used as similar looking capsules. The drugs and placebo will be given for one year or till the end points of the study.
Active Comparator: 2, secondary prophylaxis

Patients with liver cirrhosis with ascites having history of prior SBP will be included in this arm.

They will be randomized between probiotics and norfloxacin.
Drug: Probiotics and Norfloxacin
The Probiotics used in this study will be VSL#3. The control will be given similar looking capsules containing galactose powder.It will be used in the form of capsules. A total dose of 450 billions CFU will be used. Norfloxacin, 400 mg /day, will also be used as similar looking capsules. The drugs will be given for one year or till the end points of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Development of an episode of SBP, completion of one year, or death
Time Frame: till end points
till end points

Secondary Outcome Measures

Outcome Measure
development of encephalopathy, variceal bleeding and renal failure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, New Delhi

Investigators

  • Principal Investigator: Subrat K Acharya, DM, All India Institute of Medical Sciences, New Delhi, India

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Study Registration Dates

First Submitted

May 13, 2008

First Submitted That Met QC Criteria

May 14, 2008

First Posted (Estimate)

May 15, 2008

Study Record Updates

Last Update Posted (Estimate)

May 15, 2008

Last Update Submitted That Met QC Criteria

May 14, 2008

Last Verified

May 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SBP-Probiotics rct

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