Clinical trial NCT01687543: Probiotics for Reduction of Infections With Clostridium Difficile in Critically Ill Patients
Official title: Probiotics for Reduction of Colonisation With Clostridium Difficile in Antibiotic Treated Intensive Care Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Clostridium Difficile Colonisation
Impact of Enteral Probiotics on Certain Lab Parameters
Keywords: Clostridium difficile
WBC
CRP
Lactate
Urea
Creatinine
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
First posted: 2012-09-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility 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

Primary outcomes:
measure: Differences in emerging cases of Clostridium difficile
timeFrame: Throughout the ICU stay, expected mean LOS 10 days
Secondary outcomes:
measure: White blood cells
timeFrame: Throughout the ICU , expected mean LOS 10 days
measure: C Reactive Protein
timeFrame: Throughout the ICU , expected mean LOS 10 days
measure: Creatinine
timeFrame: Throughout the ICU , expected mean LOS 10 days
measure: Urea
timeFrame: Throughout the ICU , expected mean LOS 10 days
measure: Lactate
timeFrame: Throughout the ICU , expected mean LOS 10 days
measure: Ventilator days
timeFrame: Throughout the ICU stay, expected mean LOS 10 days
measure: Length of stay ICU
timeFrame: Length of ICU stay, about 10 days in accordance with a prior similar study
measure: Length of Hospital stay
timeFrame: Within six months from date of ICU admission
measure: Survival
timeFrame: Six months
measure: Diarrhea and obstipation
timeFrame: Throughout the ICU stay, expected mean LOS 10 days
Other outcomes:
Locations:
city: Helsingborg
country: Sweden
facility: Intensive Care Unit, Helsingborg Hospital
city: Kristianstad
country: Sweden
facility: Intensive Care Unit, Kristianstad Central hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Umeå
country: Sweden
facility: Dept of Anesthesia & Intensive Care, University Hospital of Norrland
Study officials:
affiliation: Lund University, Lund, Sweden
name: Bengt Klarin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.