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

NCT ID: NCT01687543

Last Updated: 2017-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2017-10-01

Brief Summary

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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

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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.

Conditions

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Clostridium Difficile Colonisation Impact of Enteral Probiotics on Certain Lab Parameters

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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

Group Type EXPERIMENTAL

L. plantarum 299 and L. plantarum 299v (+maltodextrin)

Intervention Type DIETARY_SUPPLEMENT

A suspension of Lactobacillus plantarum 299 and Lactobacillus plantarum 299v together with maltodextrin is distributed to the patients twice a day.

Control

Patients will be given only the dissolved maltodextrin in water through the nasogastric tube. Patients randomized 1:1 between groups

Group Type PLACEBO_COMPARATOR

Maltodextrin

Intervention Type OTHER

A suspension of maltodextrin (as placebo control) is distributed to the patients twice a day.

Interventions

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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.

Intervention Type DIETARY_SUPPLEMENT

Maltodextrin

A suspension of maltodextrin (as placebo control) is distributed to the patients twice a day.

Intervention Type OTHER

Other Intervention Names

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Lactobacillus plantarum 299 Lactobacillus plantarum 299v Maltodextrin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lund University

OTHER

Sponsor Role collaborator

Region Skane

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bengt Klarin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University, Lund, Sweden

Locations

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Intensive Care Unit, Helsingborg Hospital

Helsingborg, , Sweden

Site Status

Intensive Care Unit, Kristianstad Central hospital

Kristianstad, , Sweden

Site Status

Lund University Hospital

Lund, , Sweden

Site Status

Dept of Anesthesia & Intensive Care, University Hospital of Norrland

Umeå, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type BACKGROUND
PMID: 18840110 (View on PubMed)

Related Links

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http://www.probi.se

Producers of the study products

Other Identifiers

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ProENT11

Identifier Type: -

Identifier Source: org_study_id