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

Primary Purpose

Spontaneous Bacterial Peritonitis, Liver Cirrhosis

Status
Unknown status
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Probiotics and Placebo
Probiotics and Norfloxacin
Sponsored by
All India Institute of Medical Sciences, New Delhi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Spontaneous Bacterial Peritonitis focused on measuring probiotics, cirrhosis, prophylaxis, cirrhotic, patients, with, ascites, using

Eligibility Criteria

13 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • All India Institute of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

1, Primary prophylaxis

2, secondary prophylaxis

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Development of an episode of SBP, completion of one year, or death

Secondary Outcome Measures

development of encephalopathy, variceal bleeding and renal failure

Full Information

First Posted
May 13, 2008
Last Updated
May 14, 2008
Sponsor
All India Institute of Medical Sciences, New Delhi
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1. Study Identification

Unique Protocol Identification Number
NCT00678613
Brief Title
Role of Probiotics in the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Randomized Placebo Control Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2008
Overall Recruitment Status
Unknown status
Study Start Date
July 2007 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
All India Institute of Medical Sciences, New Delhi

4. Oversight

5. Study Description

Brief Summary
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.
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 : completion of one year. development of an episode of SBP. Death.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spontaneous Bacterial Peritonitis, Liver Cirrhosis
Keywords
probiotics, cirrhosis, prophylaxis, cirrhotic, patients, with, ascites, using

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Masking
Double
Allocation
Randomized
Enrollment
250 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
1, Primary prophylaxis
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
2, secondary prophylaxis
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Probiotics and Placebo
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Probiotics and Norfloxacin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Development of an episode of SBP, completion of one year, or death
Time Frame
till end points
Secondary Outcome Measure Information:
Title
development of encephalopathy, variceal bleeding and renal failure

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Subrat K Acharya, DM
Phone
91-11-2658-8500
Ext
4934
Email
subratacharya2004@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Subrat K Acharya, DM
Organizational Affiliation
All India Institute of Medical Sciences, New Delhi, India
Official's Role
Principal Investigator
Facility Information:
Facility Name
All India Institute of Medical Sciences
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110029
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Subrat K Acharya, DM
Phone
91-11-2658-8500
Ext
4934
Email
subratacharya2004@yahoo.com
First Name & Middle Initial & Last Name & Degree
Ramesh Kumar, MD
Phone
99-6840-7350
Email
drramesh1977@yahoo.com
First Name & Middle Initial & Last Name & Degree
Ramesh Kumar, MD
First Name & Middle Initial & Last Name & Degree
Geeta Satapathy, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
16979776
Citation
Riordan SM, Williams R. The intestinal flora and bacterial infection in cirrhosis. J Hepatol. 2006 Nov;45(5):744-57. doi: 10.1016/j.jhep.2006.08.001. Epub 2006 Sep 1. No abstract available.
Results Reference
background
PubMed Identifier
15723320
Citation
Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005 Mar;41(3):422-33. doi: 10.1002/hep.20632.
Results Reference
background
PubMed Identifier
12217598
Citation
Chiva M, Soriano G, Rochat I, Peralta C, Rochat F, Llovet T, Mirelis B, Schiffrin EJ, Guarner C, Balanzo J. Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis. J Hepatol. 2002 Oct;37(4):456-62. doi: 10.1016/s0168-8278(02)00142-3.
Results Reference
background
PubMed Identifier
15122774
Citation
Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004 May;39(5):1441-9. doi: 10.1002/hep.20194.
Results Reference
background
PubMed Identifier
12134110
Citation
Rayes N, Seehofer D, Hansen S, Boucsein K, Muller AR, Serke S, Bengmark S, Neuhaus P. Early enteral supply of lactobacillus and fiber versus selective bowel decontamination: a controlled trial in liver transplant recipients. Transplantation. 2002 Jul 15;74(1):123-7. doi: 10.1097/00007890-200207150-00021.
Results Reference
background

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

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