Overview

This trial is active, not recruiting.

Conditions clostridium difficile colonisation, impact of enteral probiotics on certain lab parameters
Treatments l. plantarum 299 and l. plantarum 299v (+maltodextrin), maltodextrin
Sponsor Region Skane
Collaborator Lund University
Start date June 2012
End date April 2017
Trial size 250 participants
Trial identifier NCT01687543, ProENT11

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose prevention
Arm
(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
l. plantarum 299 and l. plantarum 299v (+maltodextrin) Lactobacillus plantarum 299
A suspension of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v together with maltodextrin is distributed to the patients twice a day.
(Placebo Comparator)
Patients will be given only the dissolved maltodextrin in water through the nasogastric tube. Patients randomized 1:1 between groups
maltodextrin
A suspension of maltodextrin (as placebo control) is distributed to the patients twice a day.

Primary Outcomes

Measure
Differences in emerging cases of Clostridium difficile
time frame: Throughout the ICU stay, expected mean LOS 10 days

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Probiotics for Reduction of Colonisation With Clostridium Difficile in Antibiotic Treated Intensive Care Patients
Principal investigator Bengt Klarin, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Region Skane.