Probiotic Approach to Combat multi-resistent Enterocci: a cross-over clinical trial on the effect of probiotics on nosocomial spread of CC17 Enterococcus faecium

ISRCTN ISRCTN58761709
DOI https://doi.org/10.1186/ISRCTN58761709
Secondary identifying numbers 06-274
Submission date
30/05/2007
Registration date
30/05/2007
Last edited
04/07/2019
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

Ms M.J.A. de Regt
Scientific

University Medical Centre Utrecht (UMCU)
Department of Medical Microbiology
P.O. Box 85500
Utrecht
3508 GA
Netherlands

Phone +31 (0)30 2505006
Email m.deregt@umcutrecht.nl

Study information

Study designProspective cohort study existing of two periods (period A with no intervention and period B with probiotics as intervention) executed in two wards in a cross-over design.
Primary study designObservational
Secondary study designCohort study
Study setting(s)Hospital
Study typeTreatment
Scientific titleProbiotic Approach to Combat multi-resistent Enterocci: a cross-over clinical trial on the effect of probiotics on nosocomial spread of CC17 Enterococcus faecium
Study acronymPACE
Study objectivesProbiotics, defined as microbial food supplements that improve intestinal colonisation resistance, will decrease incidence and prevalence of gut colonisation with CC17 ampicillin-resistant enterococcus faecium (ARE) in hospitalised patients.
Ethics approval(s)The trial was approved by the Medical Ethical Commission (METC) of the University Medical Center Utrecht on the 6th March 2007 (ref: 06-274).
Health condition(s) or problem(s) studiedAmpicillin-resistant Enterococcus faecium (ARE) infection
InterventionThe name of the probiotic product that is used in this trial is Ecologic® AAD, a multi-species probiotic powder, containing ten species (Bifidobacterium bifidum, Bifidobacterium lactis (2x), Enterococcus faecium, Lactobacillus acidophilus (2x), Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus salivarius) at 10^9 cfu/gr, which will be added to the diet of all admissions in study period B, the intervention period. Winclove Bio Industries BV has been producing multi-species probiotic powders for almost fifteen years. The lactic acid bacteria used are all commercially available in other products. All components are legally admitted as food additives or food components. The product that will be used in this study, Ecologic® AAD, is notified as dietary medical food for special medical purposes.

Probiotics are considered to be safe for the host. In the European workshop on the safety aspects of lactic acid bacteria used as probiotics in 1999, it was concluded that the available evidence does not indicate any health risk posed by ingestion of lactic acid bacteria. The long history of consumption, the available epidemiological data, clinical trials and acute toxicity studies all suggest that lactic acid bacteria, commonly occurring in fermented and dairy foods (green olives, sauer-kraut, yoghurt, cheese, etc.) and used in current probiotics (lactobacilli and bifidobacteria added to yoghurt, etc.), are safe. In addition antibiotic susceptibility testing ensures that the used lactic acid bacteria are unlikely to influence undesirable antibiotic gene transfer cascades in vivo and are not expected to cause any risk for human health with regard to antibiotic resistance. In contrast, we hypothesise that probiotics can reduce the spread of multi-resistant nosocomial pathogens like CC17 E. faecium by preventing intestinal colonisation and thereby will contribute to reducing occurrence of nosocomial infections and possibilities for horizontal transfer of resistance genes.

In the intervention period twice a day a sachet containing 5 gram of the probiotic powder has to be consumed, preferably on an empty stomach in de morning and before going to sleep. When oral antibiotics are used, probiotics should be given at least two hours before or after antibiotics. The nursing staff will dissolve the probiotic powder in lucid water and will sign a special form when the patient has taken the product. In the case of gastric and duodenal tubes the dissolved product can be given via the tube. The product will be given as soon as oral consent is given after admission to one of the study wards until discharge of the ward.

During the admission patients are screened for ARE colonisation by a perianal swab on admission, before discharge and twice weekly during admission. When a patient discharged from the ward, no further follow-up will take place.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Probiotics
Primary outcome measureThe difference in acquisition rate of rectal ARE-colonisation between periods A and B. Acquisition of ARE-colonisation is defined as a patient that is not colonised on admission that acquires colonisation during admission. This is measured by a perianal swab within 48 hours after admission and within 72 hours before discharge. At the end of the study, the total acquisition rate of period A is compared with the total acquisition rate of period B to investigate if there is a difference. This analysis is performed for both separate wards.
Secondary outcome measuresThe difference in prevalence of rectal ARE-colonisation between periods A and B. Twice weekly all patients are screened for ARE-colonisation. On these days the prevalence of ARE-colonisation can be determined. Because of natural fluctuations, these prevalences will differ per day. Therefore, at the end of the study the mean prevalence and the distribution of ARE-colonisation in period A will be compared with period B to investigate if there is a difference that can be explained by the use of the investigational product. This analysis is performed for both separate wards.
Overall study start date01/05/2007
Completion date01/02/2008

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexNot Specified
Target number of participants640
Total final enrolment661
Key inclusion criteriaAll admissions on two wards (gastroenterology/nephrology and geriatrics) of the University Medical Centre Utrecht, where ARE colonisation is endemic.
Key exclusion criteriaDoes not comply with the above inclusion criteria
Date of first enrolment01/05/2007
Date of final enrolment01/02/2008

Locations

Countries of recruitment

  • Netherlands

Study participating centre

University Medical Centre Utrecht (UMCU)
Utrecht
3508 GA
Netherlands

Sponsor information

University Medical Centre Utrecht (UMCU) (The Netherlands)
Hospital/treatment centre

Department of Medical Microbiology
P.O. Box 85500
Utrecht
3508 GA
Netherlands

Website http://www.umcutrecht.nl/zorg/
ROR logo "ROR" https://ror.org/04pp8hn57

Funders

Funder type

Government

European Union (Belgium)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/07/2010 04/07/2019 Yes No

Editorial Notes

04/07/2019: Publication reference and total final enrolment added.