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Probiotics for Reduction of Infections With Clostridium Difficile in Critically Ill Patients (ProbiEnt)

This study is ongoing, but not recruiting participants.
Lund University
Information provided by (Responsible Party):
Region Skane Identifier:
First received: August 28, 2012
Last updated: April 11, 2017
Last verified: April 2017

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.

Condition Intervention
Clostridium Difficile Colonisation
Impact of Enteral Probiotics on Certain Lab Parameters
Dietary Supplement: L. plantarum 299 and L. plantarum 299v (+maltodextrin)
Other: Maltodextrin

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Prevention
Official Title: Probiotics for Reduction of Colonisation With Clostridium Difficile in Antibiotic Treated Intensive Care Patients

Further study details as provided by Region Skane:

Primary Outcome Measures:
  • 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

Secondary Outcome Measures:
  • White blood cells [ Time Frame: Throughout the ICU , expected mean LOS 10 days ]
    Samples taken at admission or inclusion and then daily

  • C Reactive Protein [ Time Frame: Throughout the ICU , expected mean LOS 10 days ]
    Samples taken at admission or inclusion and then daily

  • Creatinine [ Time Frame: Throughout the ICU , expected mean LOS 10 days ]
    Samples taken at admission or inclusion and then daily

  • Urea [ Time Frame: Throughout the ICU , expected mean LOS 10 days ]
    Samples taken at admission or inclusion and then daily

  • Lactate [ Time Frame: Throughout the ICU , expected mean LOS 10 days ]
    Samples taken at admission or inclusion and then daily

  • Ventilator days [ Time Frame: Throughout the ICU stay, expected mean LOS 10 days ]
    Records are held for how long the patients require mechanical ventilation

  • Length of stay ICU [ Time Frame: Length of ICU stay, about 10 days in accordance with a prior similar study ]
    Length of stay is recorded for the ICU as well as for the Hospital stay

  • Length of Hospital stay [ Time Frame: Within six months from date of ICU admission ]
    Length of stay is recorded for the Hospital as well as for the ICU stay

  • Survival [ Time Frame: Six months ]
    For participating patients the status of survival or non survival at days 28 and 180 (six months) will be recorded

  • Diarrhea and obstipation [ Time Frame: Throughout the ICU stay, expected mean LOS 10 days ]

    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

Estimated Enrollment: 250
Study Start Date: June 2012
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Probiotics
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
Dietary Supplement: L. plantarum 299 and L. plantarum 299v (+maltodextrin)
A suspension of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v together with maltodextrin is distributed to the patients twice a day.
Other Names:
  • Lactobacillus plantarum 299
  • Lactobacillus plantarum 299v
  • Maltodextrin
Placebo Comparator: Control
Patients will be given only the dissolved maltodextrin in water through the nasogastric tube. Patients randomized 1:1 between groups
Other: Maltodextrin
A suspension of maltodextrin (as placebo control) is distributed to the patients twice a day.

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01687543

Intensive Care Unit, Helsingborg Hospital
Helsingborg, Sweden, SE 251 87
Intensive Care Unit, Kristianstad Central hospital
Kristianstad, Sweden, SE 291 85
Lund University Hospital
Lund, Sweden, SE 22185
Dept of Anesthesia & Intensive Care, University Hospital of Norrland
Umeå, Sweden, SE-901 85
Sponsors and Collaborators
Region Skane
Lund University
Principal Investigator: Bengt Klarin, MD, PhD Lund University, Lund, Sweden
  More Information

Additional Information:
Responsible Party: Region Skane Identifier: NCT01687543     History of Changes
Other Study ID Numbers: ProENT11
Study First Received: August 28, 2012
Last Updated: April 11, 2017

Keywords provided by Region Skane:
Clostridium difficile
Creatinine processed this record on May 25, 2017