Clostridium Difficile ColonisationProbiEntNCT01687543
Probiotics for Reduction of Infections With Clostridium Difficile in Critically Ill Patients
A study testing L. plantarum 299 and L. plantarum 299v (+maltodextrin) and Maltodextrin in people with Clostridium Difficile Colonisation and Impact of Enteral Probiotics on Certain Lab Parameters, run by Region Skane at 4 sites in Sweden.
Trial summary
Symptoms of Clostridium difficile infection is almost always induced as a complication to the use of antibiotics. Most ICU patients are given antibiotics. Probiotics has the ability to improve conditions in the gut and it has been shown in some smaller studies that overgrowth of C. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Colonisation, Impact of Enteral Probiotics on Certain Lab Parameters
- What is being tested?
- L. plantarum 299 and L. plantarum 299v (+maltodextrin) and Maltodextrin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 4 sitesSweden
- Study dates
- Jun 2012to 1 Oct 2017
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Anticipated need for intensive care 3 days or longer
- Patients condition allowing enteral nutrition to be started within 24 h from ICU admission
- Antibiotics on-going or planned
Who cannot join
- Known positive test for Clostridium difficile within the last week
- Known ulcers in the mouth, oropharynx, esophagus and stomach
- Known immune deficiencies
- Enteral nutrition contra indicated
- Pancreatitis as admission diagnosis at the hospital or at the ICU
- ICU admission earlier during this period of illness Patient being moribund
Trial locations and contacts
4 sites in 1 country.
Sweden4 sites
Intensive Care Unit, Helsingborg Hospital
Helsingborg, SE 251 87
Intensive Care Unit, Kristianstad Central hospital
Kristianstad, SE 291 85
Lund University Hospital
Lund, SE 22185
Dept of Anesthesia & Intensive Care, University Hospital of Norrland
Umeå, SE-901 85
About this study
Official title: Probiotics for Reduction of Colonisation With Clostridium Difficile in Antibiotic Treated Intensive Care Patients
Symptoms of Clostridium difficile infection is almost always induced as a complication to the use of antibiotics. Most ICU patients are given antibiotics.
Probiotics has the ability to improve conditions in the gut and it has been shown in some smaller studies that overgrowth of C. difficile can be reduced or prevented.
Read more
In this study the intention is to show with sufficient statistical power that a mixture of two otherwise well studied probiotic strains reduces or prevents the incidence of emerging colonisation with C. difficile in critical ill patients on antibiotics.
Half of the patients will be given a mixture of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v twice daily and the rest a placebo mixture.
Rectal swabs or faeces will be analysed for C.difficile and its toxins and the incidence of new cases will be compared for the two groups.
White blood cells (WBC´s), C reactive protein (CRP), lactate, urea, and creatinine will be followed daily as well as antibiotics, corticosteroids and all acid reducing medication.
Nutrition, enteral and total, and bowel habits will be recorded.
Read the detailed description
Infections with Clostridium difficile is considered to be the most frequent health care associated bacterial infection. Almost all cases are connected to the use of antibiotics.
The spectra of symptoms of infection reaches from loose stools to sepsis and death. It is estimated that about 5% of the population are carriers without symptoms.
Elderly people are more likely to be diagnosed with C. difficile infections and as about 50 % of ICU admissions (at least in Sweden) are patients aged 64 years or older C. difficile is also an ICU issue.
Probiotic bacteria given to antibiotic treated patients results in fever cases of infection with C. difficile as we and others have shown in some small studies. Due to a low statistical power in our former study this multicentre study is calculated to be large enough to fulfil statistical requirements.
Adult patients with an expected length of stay in intensive care for three days or more can be included.
Primary objective is to find emerging cases of colonisation with C. difficile and consequent symptoms of infection such as diarrhoea.
Cultures and toxin analyses will be taken at inclusion and every second day till day 13 and then every third or fourth day depending on length of ICU stay. Positive cases will be given antibiotics according to normal routines.
No other cultures are collected per protocol but all cultures will be recorded and results will be analysed in order to find any connection between treatment and reduction of secondary infections.
In our earlier small study we found an improved and normalised gut barrier function for those patients that were given probiotic bacteria compared to a worsened, scattered pattern for the placebo group. This is probably why we found that inflammatory parameters improved for the probiotics group while those parameters remained elevated for the control patients. The same goes for creatinine, urea and lactate. This is why we will record those parameters together with blood gas analyses in this expanded study.
Antibiotics and medication with corticosteroids, proton pump inhibitors or other acid reducing preparations, All nutritive prescriptions (enteral formulas and IV solutions as well as medical preparations containing glucose or fat) will be recorded and compared to actually given nutrients.
Bowel movements frequency and consistency will be recorded and compared between groups.
- Conditions
- Clostridium Difficile Colonisation, Impact of Enteral Probiotics on Certain Lab Parameters
- Being tested
- L. plantarum 299 and L. plantarum 299v (+maltodextrin), Maltodextrin
- Keywords
- Clostridium difficile, WBC, CRP, Lactate, Urea, Creatinine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L. plantarum 299 and L. plantarum 299v (+maltodextrin)Dietary supplement
Also called Lactobacillus plantarum 299, Lactobacillus plantarum 299v, Maltodextrin
A suspension of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v together with maltodextrin is distributed to the patients twice a day.
MaltodextrinOther
A suspension of maltodextrin (as placebo control) is distributed to the patients twice a day.
| Study group | Role | What they receive |
|---|---|---|
| Probiotics | Experimental | Patients will be given a mixture of maltodextrin ( a starch product often used i alimentary products) and two strains of probiotic bacteria ( L. plantarum 299 and L. plantarum 299v ) dissolved in water through a nasogastric tube. Patients randomized 1:1 between groups Receives: Dietary Supplement: L. plantarum 299 and L. plantarum 299v (+maltodextrin) |
| Control | Placebo comparator | Patients will be given only the dissolved maltodextrin in water through the nasogastric tube. Patients randomized 1:1 between groups Receives: Other: Maltodextrin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in emerging cases of Clostridium difficile
Emerging cases of Clostridium difficile, identified as positive cultures and/or toxin tests
Measured: Throughout the ICU stay, expected mean LOS 10 days
Secondary outcomes (10)
White blood cells
Samples taken at admission or inclusion and then daily
Measured: Throughout the ICU , expected mean LOS 10 days
C Reactive Protein
Samples taken at admission or inclusion and then daily
Measured: Throughout the ICU , expected mean LOS 10 days
Creatinine
Samples taken at admission or inclusion and then daily
Measured: Throughout the ICU , expected mean LOS 10 days
Urea
Samples taken at admission or inclusion and then daily
Measured: Throughout the ICU , expected mean LOS 10 days
Lactate
Samples taken at admission or inclusion and then daily
Measured: Throughout the ICU , expected mean LOS 10 days
Ventilator days
Records are held for how long the patients require mechanical ventilation
Measured: Throughout the ICU stay, expected mean LOS 10 days
Length of stay ICU
Length of stay is recorded for the ICU as well as for the Hospital stay
Measured: Length of ICU stay, about 10 days in accordance with a prior similar study
Length of Hospital stay
Length of stay is recorded for the Hospital as well as for the ICU stay
Measured: Within six months from date of ICU admission
Survival
For participating patients the status of survival or non survival at days 28 and 180 (six months) will be recorded
Measured: Six months
Diarrhea and obstipation
As ICU patients tend to display diarrhea as well as obstipation the frequency and consistency of stools will be recorded.
Probiotics are anticipated to stabilise bowel function
Measured: Throughout the ICU stay, expected mean LOS 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2012 (estimated)
- Study startJun 2012
- Primary completionJun 2017
- Study completion1 Oct 2017
Why it stopped: Too low inclusion rate and several sites did not comply
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile ColonisationStudies of the same condition, open and under way.
- More trials run by Region SkaneThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University
- Responsible party
- Sponsor
- Investigators
- Bengt Klarin, MD, PhD, Principal investigator, Lund University, Lund, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01687543
- Sponsor's protocol ID
- ProENT11
- Acronym
- ProbiEnt
- Status last verified
- Oct 2017
- First submitted
- 28 Aug 2012
- Last updated
- 5 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Klarin B, Wullt M, Palmquist I, Molin G, Larsson A, Jeppsson B. Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics. Acta Anaesthesiol Scand. 2008 Sep;52(8):1096-102. doi: 10.1111/j.1399-6576.2008.01748.x.
PubMed 18840110
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Probiotics for Reduction of Colonisation With Clostridium Difficile in Antibiotic Treated Intensive Care Patients
- ClinicalTrials.gov ID
- NCT01687543
- Acronym / sponsor ID
- ProbiEnt / ProENT11
- Conditions
- Clostridium Difficile Colonisation, Impact of Enteral Probiotics on Certain Lab Parameters
- Keywords
- Clostridium difficile, WBC, CRP, Lactate, Urea, Creatinine
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Too low inclusion rate and several sites did not comply
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Collaborators
- Lund University
- Study start
- Jun 2012
- Primary completion
- Jun 2017 (actual)
- Study completion
- 1 Oct 2017 (actual)
- First posted
- 19 Sep 2012 (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.
Symptoms of Clostridium difficile infection is almost always induced as a complication to the use of antibiotics. Most ICU patients are given antibiotics.
Probiotics has the ability to improve conditions in the gut and it has been shown in some smaller studies that overgrowth of C. difficile can be reduced or prevented.
In this study the intention is to show with sufficient statistical power that a mixture of two otherwise well studied probiotic strains reduces or prevents the incidence of emerging colonisation with C. difficile in critical ill patients on antibiotics.
Half of the patients will be given a mixture of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v twice daily and the rest a placebo mixture.
Rectal swabs or faeces will be analysed for C.difficile and its toxins and the incidence of new cases will be compared for the two groups.
White blood cells (WBC´s), C reactive protein (CRP), lactate, urea, and creatinine will be followed daily as well as antibiotics, corticosteroids and all acid reducing medication.
Nutrition, enteral and total, and bowel habits will be recorded.
Detailed description
Infections with Clostridium difficile is considered to be the most frequent health care associated bacterial infection. Almost all cases are connected to the use of antibiotics.
The spectra of symptoms of infection reaches from loose stools to sepsis and death. It is estimated that about 5% of the population are carriers without symptoms.
Elderly people are more likely to be diagnosed with C. difficile infections and as about 50 % of ICU admissions (at least in Sweden) are patients aged 64 years or older C. difficile is also an ICU issue.
Probiotic bacteria given to antibiotic treated patients results in fever cases of infection with C. difficile as we and others have shown in some small studies. Due to a low statistical power in our former study this multicentre study is calculated to be large enough to fulfil statistical requirements.
Adult patients with an expected length of stay in intensive care for three days or more can be included.
Primary objective is to find emerging cases of colonisation with C. difficile and consequent symptoms of infection such as diarrhoea.
Cultures and toxin analyses will be taken at inclusion and every second day till day 13 and then every third or fourth day depending on length of ICU stay. Positive cases will be given antibiotics according to normal routines.
No other cultures are collected per protocol but all cultures will be recorded and results will be analysed in order to find any connection between treatment and reduction of secondary infections.
In our earlier small study we found an improved and normalised gut barrier function for those patients that were given probiotic bacteria compared to a worsened, scattered pattern for the placebo group. This is probably why we found that inflammatory parameters improved for the probiotics group while those parameters remained elevated for the control patients. The same goes for creatinine, urea and lactate. This is why we will record those parameters together with blood gas analyses in this expanded study.
Antibiotics and medication with corticosteroids, proton pump inhibitors or other acid reducing preparations, All nutritive prescriptions (enteral formulas and IV solutions as well as medical preparations containing glucose or fat) will be recorded and compared to actually given nutrients.
Bowel movements frequency and consistency will be recorded and compared between groups.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotics | Experimental | Dietary Supplement: L. plantarum 299 and L. plantarum 299v (+maltodextrin)Patients will be given a mixture of maltodextrin ( a starch product often used i alimentary products) and two strains of probiotic bacteria ( L. plantarum 299 and L. plantarum 299v ) dissolved in water through a nasogastric tube. Patients randomized 1:1 between groups |
| Control | Placebo comparator | Other: MaltodextrinPatients will be given only the dissolved maltodextrin in water through the nasogastric tube. Patients randomized 1:1 between groups |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Anticipated need for intensive care 3 days or longer
- Patients condition allowing enteral nutrition to be started within 24 h from ICU admission
- Antibiotics on-going or planned
Key exclusion criteria (6 listed)
- Known positive test for Clostridium difficile within the last week
- Known ulcers in the mouth, oropharynx, esophagus and stomach
- Known immune deficiencies
- Enteral nutrition contra indicated
- Pancreatitis as admission diagnosis at the hospital or at the ICU
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 |
|---|---|---|
| L. plantarum 299 and L. plantarum 299v (+maltodextrin)Also: Lactobacillus plantarum 299, Lactobacillus plantarum 299v, MaltodextrinA suspension of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v together with maltodextrin is distributed to the patients twice a day. | Dietary supplement | Probiotics |
| MaltodextrinA suspension of maltodextrin (as placebo control) is distributed to the patients twice a day. | Other | Control |
Primary outcome
Differences in emerging cases of Clostridium difficile
Time frame: Throughout the ICU stay, expected mean LOS 10 days
Emerging cases of Clostridium difficile, identified as positive cultures and/or toxin tests
10 secondary outcomes
White blood cells
Time frame: Throughout the ICU , expected mean LOS 10 days
C Reactive Protein
Time frame: Throughout the ICU , expected mean LOS 10 days
Creatinine
Time frame: Throughout the ICU , expected mean LOS 10 days
Urea
Time frame: Throughout the ICU , expected mean LOS 10 days
Lactate
Time frame: Throughout the ICU , expected mean LOS 10 days
Ventilator days
Time frame: Throughout the ICU stay, expected mean LOS 10 days
Length of stay ICU
Time frame: Length of ICU stay, about 10 days in accordance with a prior similar study
Length of Hospital stay
Time frame: Within six months from date of ICU admission
Survival
Time frame: Six months
Diarrhea and obstipation
Time frame: Throughout the ICU stay, expected mean LOS 10 days
Results and safety
The study was stopped early (reason given: Too low inclusion rate and several sites did not comply). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Background: PubMed 18840110Klarin B, Wullt M, Palmquist I, Molin G, Larsson A, Jeppsson B. Lactobacillus plantarum 299v reduces colonisation of Clostridium difficile in critically ill patients treated with antibiotics. Acta Anaesthesiol Scand. 2008 Sep;52(8):1096-102. doi: 10.1111/j.1399-6576.2008.01748.x.
- Producers of the study productsLink provided by the sponsor.
Related trials for Clostridium Difficile Colonisation
Not yet recruiting
Study of Factors Influencing the Dynamics of Colonisation and Decolonisation of the Digestive Tract by Clostridioides Difficile in Infants
Bacteria Infection Mechanism
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.
Bengt Klarin, MD, PhD principal investigator
Lund University, Lund, Sweden
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L. plantarum 299 and L. plantarum 299v (+maltodextrin) and Maltodextrin in people with Clostridium Difficile Colonisation and Impact of Enteral Probiotics on Certain Lab Parameters, run by Region Skane at 4 sites in Sweden.
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 3 inclusion and 6 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: stopped early, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Sweden. 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.
Are results available for this study?
The study was stopped early (reason given: Too low inclusion rate and several sites did not comply). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in emerging cases of Clostridium difficile (time frame: Throughout the ICU stay, expected mean LOS 10 days). 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 NCT01687543, which also lists 1 linked publication.
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 5 Oct 2017.