Can Lactobacillus plantarum 299v in fermented oat meal gruel prevent overgrowth of Clostridium difficile in the Gastrointestinal (GI) tract in antibiotic treated critically ill patients? [Kan Lactobacillus Plantarum 299v i fermenterad havrevälling motverka överväxt av Clostridium Difficile i magtarmkanalen hos antibiotikabehandlade kritiskt sjuka patienter?]

ISRCTN	ISRCTN85655545
DOI	https://doi.org/10.1186/ISRCTN85655545
Protocol serial number	PROMAX 2
Sponsor	Probi AB (Sweden)
Funders	Probi AB (Sweden), Region Skane (Sweden), The Scandinavian Society for Antimicrobial Chemotherapy Foundation

Submission date: 12/09/2007
Registration date: 17/09/2007
Last edited: 02/09/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Bengt Klarin
Scientific

Department of Anaesthesiology and Intensive Care
Lund University Hospital
Lund
SE-221 85
Sweden

Phone	+46 (0)46 17 19 49
Email	Bengt.Klarin@med.lu.se

Study information

Primary study design	Interventional
Study design	Randomised, double blind placebo controlled multi-centre study
Secondary study design	Randomised controlled trial
Scientific title	Can Lactobacillus plantarum 299v in fermented oat meal gruel prevent overgrowth of Clostridium difficile in the Gastrointestinal (GI) tract in antibiotic treated critically ill patients? [Kan Lactobacillus Plantarum 299v i fermenterad havrevälling motverka överväxt av Clostridium Difficile i magtarmkanalen hos antibiotikabehandlade kritiskt sjuka patienter?]
Study objectives	By giving a probiotic bacterium with known ability to establish in the GI tract also in antibiotic-treated critically ill there will be a reduction of the incidence of Clostridium difficile in Intensive Care Unit (ICU) patients on antibiotics.
Ethics approval(s)	Final ethical approval received on the 8th October 2001 from: 1. The Human Ethics Committee at Lund University (ref: LU 676-00) 2. The Human Ethics Committee at the University of Gothemburg (ref: Gbg M 123-01)
Health condition(s) or problem(s) studied	Overgrowth of C. difficile in GI tract of antibiotic-treated ICU patients
Intervention	1. Active group receives a fermented oatmeal formula containing 8 x 10^8 colony forming units (cfu)/ml of Lactobacillus plantarum 299v 2. Control product contains no bacteria. Lactic acid has been added to reach the same pH as the active product The patients are given six 100 ml doses of the study product at twelve hours intervals and then 50 ml twice a day as long as they are in the ICU.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Lactobacillus plantarum 299v
Primary outcome measure(s)	To study the impact of L plantarum 299v on emerging cases of C. difficile in ICU patients compared to those receiving a placebo product. The primary outcome is validated over the whole period in the Intensive Care Unit and cultures from faeces are taken twice a week. Overgrowth or colonisation with C difficile can appear in the range from a few days to several weeks of antibiotic treatment and even after the medication has ended.
Key secondary outcome measure(s)	1. Study gut barrier function 2. Recovery rates of L plantarum 299v, and other effects on the gut microbiota 3. Systemic infections 4. Immune response, as White Blood Cell count (WBC), C-Reactive Protein (CRP) and cytokines (Tumour Necrotising Factor [TNF], Interleukin-1 [IL-1], Interleukin-6 [IL-6] and Interleukin-10 [IL-10]) 5. Influence on metabolic parameters Gut permeability is tested at inclusion day (day 1) and on day 4 so outcome is measured on study day 4. Faecal samples are taken at enrolment and then twice a week. Recovery of added bacteria are validated for the whole Length of Stay (LOS). Due to impaired function of the bowel in critically ill patients passage time through the gut varies so much that the whole LOS will be used to evaluate colonisation with L plantarum 299v. Microbiological cultures (as tests for systemic infections) are taken on clinical grounds or at least once a week and results are summarised for the whole LOS. Infectious, inflammatory and metabolic parameters are followed by daily blood tests throughout the stay in the ICU. Daily comparisons will be performed for the active treatment and placebo groups.
Completion date	15/09/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	100
Total final enrolment	44
Key inclusion criteria	1. 18 years or older 2. Critically ill, defined by a presumed need of intensive care for three days or more 3. Not have any known positive test for C. difficile within the week before enrolment 4. Be anticipated to tolerate enteral feeding 5. Starting within 24 hours from ICU admission
Key exclusion criteria	1. Not be allergic to any of the components in the study product 2. If entereral feeding (including study product) is not started within 24 hours 3. Not be moribund
Date of first enrolment	01/12/2001
Date of final enrolment	15/09/2007

Locations

Countries of recruitment

Sweden

Study participating centre

Department of Anaesthesiology and Intensive Care

Lund
SE-221 85
Sweden

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		01/09/2008	02/09/2021	Yes	No

Editorial Notes

02/09/2021: Publication reference and total final enrolment added.