Probiotics for Reduction of Infections With Clostridium Difficile in Critically Ill Patients (ProbiEnt)
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.
Clostridium Difficile Colonisation
Impact of Enteral Probiotics on Certain Lab Parameters
Dietary Supplement: L. plantarum 299 and L. plantarum 299v (+maltodextrin)
|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|
- 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
- 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
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
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.
Placebo Comparator: Control
Patients will be given only the dissolved maltodextrin in water through the nasogastric tube. Patients randomized 1:1 between groups
A suspension of maltodextrin (as placebo control) is distributed to the patients twice a day.
Other Name: Maltodextrin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01687543
|Contact: Bengt Klarin, MD, PhD||+4646171941||Bengt.Klarin@med.lu.se|
|Contact: Anne Adolfsson, RNfirstname.lastname@example.org|
|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 email@example.com|
|Principal Investigator: Karin Olofsson, MD|
|Sub-Investigator: Therese Celander, RN|
|Sub-Investigator: Magnus Paglert, RN|
|Intensive Care Unit, Kristianstad Central hospital||Suspended|
|Kristianstad, Sweden, SE 291 85|
|Lund University Hospital||Recruiting|
|Lund, Sweden, SE 22185|
|Contact: Bengt Klarin, MD, PhD +4646171941 Bengt.Klarin@med.lu.se|
|Contact: Anne Adolfsson, RN +4646173805 firstname.lastname@example.org|
|Principal Investigator: Bengt Klarin, MD, PhD|
|Dept of Anesthesia & Intensive Care, University Hospital of Norrland||Active, not recruiting|
|Umeå, Sweden, SE-901 85|
|Principal Investigator:||Bengt Klarin, MD, PhD||Lund University, Lund, Sweden|