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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Region Skane
Sponsor:
Collaborator:
Lund University
Information provided by (Responsible Party):
Region Skane
ClinicalTrials.gov Identifier:
NCT01687543
First received: August 28, 2012
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

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.

WBC´s, 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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Probiotics for Reduction of Colonisation With Clostridium Difficile in Antibiotic Treated Intensive Care Patients

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Samples taken at admission or inclusion and then daily

  • C Reactive Protein [ Time Frame: Throughout the ICU , expected mean LOS 10 days ] [ Designated as safety issue: No ]
    Samples taken at admission or inclusion and then daily

  • Creatinine [ Time Frame: Throughout the ICU , expected mean LOS 10 days ] [ Designated as safety issue: No ]
    Samples taken at admission or inclusion and then daily

  • Urea [ Time Frame: Throughout the ICU , expected mean LOS 10 days ] [ Designated as safety issue: No ]
    Samples taken at admission or inclusion and then daily

  • Lactate [ Time Frame: Throughout the ICU , expected mean LOS 10 days ] [ Designated as safety issue: No ]
    Samples taken at admission or inclusion and then daily

  • Ventilator days [ Time Frame: Throughout the ICU stay, expected mean LOS 10 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Length of stay is recorded for the Hospital as well as for the ICU stay

  • Survival [ Time Frame: Six months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 2014
Estimated Primary Completion Date: March 2014 (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.
Other Name: Maltodextrin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01687543

Contacts
Contact: Bengt Klarin, MD, PhD +4646171941 Bengt.Klarin@med.lu.se
Contact: Anne Adolfsson, RN +4646173805 anne.adolfsson@skane.se

Locations
Sweden
Intensive Care Unit, Helsingborg Hospital Recruiting
Helsingborg, Sweden, SE 251 87
Contact: Karin Olofsson, MD    +46424062146    Karin.Olofsson@skane.se   
Contact: Therese Celander, RN    +46424062954    therese.celander@skane.se   
Principal Investigator: Karin Olofsson, MD         
Sub-Investigator: Therese Celander, RN         
Sub-Investigator: Magnus Paglert, RN         
Intensive Care Unit, Kristianstad Central hospital Recruiting
Kristianstad, Sweden, SE 291 85
Contact: Jonas Prellner, MD    +46 44 3031179    Jonas.Prellner@skane.se   
Contact: Marika Hall, RN    +46 443091149    Marika.Hall@skane.se   
Principal Investigator: Keld Brodersen, MD         
Lund University Hospital Recruiting
Lund, Sweden, SE 22185
Contact: Bengt Klarin, MD, PhD    +4646171941    Bengt.Klarin@med.lu.se   
Contact: Anne Adolfsson, RN    +4646173805    anne.adolfsson@skane.se   
Principal Investigator: Bengt Klarin, MD, PhD         
Dept of Anesthesia & Intensive Care, University Hospital of Norrland Recruiting
Umeå, Sweden, SE-901 85
Contact: Ola Winsö, MD, PhD; Professor/Consultant    +46907852466    ola.winso@anestesi.umu.se   
Contact: Mariann Haapalahti, RN    +46907853000    mariann.haapalahti@vll.se   
Sponsors and Collaborators
Region Skane
Lund University
Investigators
Principal Investigator: Bengt Klarin, MD, PhD Lund University, Lund, Sweden
  More Information

Additional Information:
Publications:
Responsible Party: Region Skane
ClinicalTrials.gov Identifier: NCT01687543     History of Changes
Other Study ID Numbers: ProENT11
Study First Received: August 28, 2012
Last Updated: August 5, 2013
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by Region Skane:
Clostridium difficile
WBC
CRP
Lactate
Urea
Creatinine

ClinicalTrials.gov processed this record on October 01, 2014