Spontaneous Bacterial PeritonitisPhase 2/3NCT00678613
Role of Probiotics in the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Randomized Placebo Control Trial
A Phase 2/3 study testing Probiotics and Norfloxacin in people with Spontaneous Bacterial Peritonitis and Liver Cirrhosis, run by All India Institute of Medical Sciences at 1 site in India.
Trial 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… Read more about this study
- Who is it for?
- Ages 13 to 65 years
- Conditions the study is for
- Spontaneous Bacterial Peritonitis, Liver Cirrhosis
- What is being tested?
- Probiotics and Norfloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 1 siteIndia
- Study dates
- Jul 2007to not given
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029
Subrat K Acharya, DM, 91-11-2658-8500 ext. 4934, subratacharya2004@yahoo.com
Ramesh Kumar, MD, 99-6840-7350, drramesh1977@yahoo.com
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Spontaneous Bacterial Peritonitis, Liver Cirrhosis
- Being tested
- Probiotics and Placebo, Probiotics and Norfloxacin
- Keywords
- probiotics, cirrhosis, prophylaxis, cirrhotic, patients, with, ascites, using
- Medical subject headings
- Liver Cirrhosis, Fibrosis, Ascites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotics and PlaceboDrug
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.
Probiotics and NorfloxacinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1, Primary prophylaxis | Placebo comparator | 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. Receives: Drug: Probiotics and Placebo |
| 2, secondary prophylaxis | Active comparator | 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. Receives: Drug: Probiotics and Norfloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Development of an episode of SBP, completion of one year, or death
Measured: till end points
Secondary outcomes (1)
development of encephalopathy, variceal bleeding and renal failure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2008 (estimated)
- Study startJul 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Spontaneous Bacterial PeritonitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- All India Institute of Medical Sciences
- Sponsor type
- University, hospital or other
- Investigators
- Subrat K Acharya, DM, Principal investigator, All India Institute of Medical Sciences, New Delhi, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00678613
- Sponsor's protocol ID
- SBP-Probiotics rct
- Status last verified
- May 2008
- First submitted
- 13 May 2008
- Last updated
- 15 May 2008
- Results posted
- No
Publications
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.
PubMed 16979776Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005 Mar;41(3):422-33. doi: 10.1002/hep.20632.
PubMed 15723320Chiva 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.
PubMed 12217598Liu 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.
PubMed 15122774Rayes 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.
PubMed 12134110
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Probiotics in the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Randomized Placebo Control Trial
- ClinicalTrials.gov ID
- NCT00678613
- Acronym / sponsor ID
- SBP-Probiotics rct
- Conditions
- Spontaneous Bacterial Peritonitis, Liver Cirrhosis
- Keywords
- probiotics, cirrhosis, prophylaxis, cirrhotic, patients, with, ascites, using
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- All India Institute of Medical SciencesUniversity, hospital or other
- Study start
- Jul 2007
- First posted
- 15 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1, Primary prophylaxis | Placebo comparator | Drug: Probiotics and PlaceboPatients 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. |
| 2, secondary prophylaxis | Active comparator | Drug: Probiotics and NorfloxacinPatients with liver cirrhosis with ascites having history of prior SBP will be included in this arm. They will be randomized between probiotics and norfloxacin. |
Who may qualify
- Ages
- 13 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotics and PlaceboThe 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. | Drug | 1, Primary prophylaxis |
| Probiotics and NorfloxacinThe 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. | Drug | 2, secondary prophylaxis |
Primary outcome
Development of an episode of SBP, completion of one year, or death
Time frame: till end points
1 secondary outcome
development of encephalopathy, variceal bleeding and renal failure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2008.
- Background: PubMed 16979776Riordan 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.
- Background: PubMed 15723320Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005 Mar;41(3):422-33. doi: 10.1002/hep.20632.
- Background: PubMed 12217598Chiva 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.
- Background: PubMed 15122774Liu 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.
- Background: PubMed 12134110Rayes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Subrat K Acharya, DM principal investigator
All India Institute of Medical Sciences, New Delhi, India
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Probiotics and Norfloxacin in people with Spontaneous Bacterial Peritonitis and Liver Cirrhosis, run by All India Institute of Medical Sciences at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 May 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Subrat K Acharya, DM (91-11-2658-8500 ext. 4934, subratacharya2004@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Development of an episode of SBP, completion of one year, or death (time frame: till end points). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00678613, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2008.