Condition category
Infections and Infestations
Date applied
07/08/2019
Date assigned
30/08/2019
Last edited
30/08/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Antibiotic resistance of Gram-negative bacteria, particularly the Enterobacteriaceae, is a major global concern. Manchester is known to have a higher spread of carbapenem-resistant Klebsiella pneumoniae which combines virulence, high transmissibility and transmissible resistance to almost all antibiotics. Traditional approaches, such as antimicrobial stewardship and infection control, are unlikely to reverse the spread of carbapenem-resistant Enterobacteriaceae. The probiotic species Lactobacillus reuteri inhibits Enterobacteriaceae and its administration reduces their counts in the infant gut. It is now used in paediatric practice to treat carriage of resistant strains of Enterobacteriaceae, including Klebsiella pneumoniae. This is a study in Manchester of immuno-competent adults known to be colonised with multi-resistant K pneumoniae. The aim is to investigate whether any falls in faecal counts of multi-resistant K pneumoniae seen after the administration of a probiotic are greater than any falls seen in the control group. The study will also investigate whether a lower proportion of the final faecal samples from probiotic-receiving than from control participants yield multi-resistant K pneumoniae on culture.

Who can participate?
Patients aged 18 or older who are immuno-competent and colonised with multi-resistant K pneumoniae

What does the study involve?
Participants are randomly allocated to be discharged from hospital with a prescription of 1 chewable probiotic tablet to take each day for 21 days, or no additional tablets at all. All participants, regardless of having been asked to take the probiotic tablet or not, need to return a faecal sample to the hospital 21 days after they have returned home from their stay. Participants are given a kit to post this sample and instructions on how to do this. The kits are pre-paid for so it does not cost participants anything to post the sample. A Research Nurse from the hospital calls participants to remind them to send the sample and also ask questions about how the participant is feeling and to check that they have taken all probiotic tablets (if allocated to this group)

What are the possible benefits and risks of participating?
There will be no direct benefit to taking part in this study. However, it is hoped that the information from this study will show the impact probiotics have on the gut count of multiresistance bacteria in the gut for future investigations. It is not expected that the participants will experience any serious adverse events related to the probiotic. These products are considered to be food and are safe for consuming. There are a number of studies with children and adults supporting this. No other risks are identified.

Where is the study run from?
1. Manchester Royal Infirmary (UK)
2. Wythenshawe Hospital (UK)

When is the study starting and how long is it expected to run for?
November 2018 to December 2019

Who is funding the study?
Healthcare Infection Society (UK)

Who is the main contact?
Dr Beatriz Duran Jimenez
beatriz.duran@mft.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Beatriz Duran Jimenez

ORCID ID

Contact details

Pharmacy
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom
+44 (0)161 291 4193
beatriz.duran@mft.nhs.uk

Type

Public

Additional contact

Mr Bradley Tallon

ORCID ID

Contact details

Clinical Trials Manager – Burns
Plastics & Critical Care
Research & Innovation
1st Floor - NIHR Building
Wythenshawe Hospital
Manchester University NHS Foundation Trust
Southmoor Road
Manchester
M23 9QZ
United Kingdom
+44 (0)161 291 5757
Bradley.tallon@mft.nhs.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

B00261

Study information

Scientific title

Randomised open-label controlled feasibility trial of probiotic in the elimination of faecal carriage carbapenemase-bearing Klebsiella pneumoniae

Acronym

PITFALL

Study hypothesis

1. To investigate whether any falls in faecal counts of a carbapenemase-bearing Klebsiella pneumoniae seen after 21 days of probiotic (Lactobacillus reuteri) administration to adults are greater than any falls seen in control adults
2. To determine whether a lower proportion of the final faecal samples from probiotic-receiving than from control subjects yields carbapenemase-bearing K pneumoniae on culture

Ethics approval

Approved 26/03/2019, North West - Greater Manchester Central Research Ethics Committee (3rd Floor, Barlow House, 4 Minshull Street, Manchester, M1 3DZ, UK; Tel: +44 (0)207 104 8007; Email: nrescommittee.northwest-gmcentral@nhs.net), REC ref: 18/NW/0863

Study design

Randomised open-label feasibility study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Patients with colonised carbapenemase-bearing Klebsiella pneumoniae

Intervention

The intervention arm will involve patients taking the probiotic (as below). The control arm involves no intervention; there is no placebo so patients will be discharged without a supplement/probiotic.

The probiotic preparation to be used will be BioGaia Gastrus tablets (BioGaia AB, Stockholm, Sweden). BioGaia Gastrus chewable tablets is a dietary supplement containing a combination of the probiotic strain Lactobacillus reuteri 17938 (Lactobacillus reuteri Protectis) and Lactobacillus reuteri ATCC PTA 6475.

Dose: 1 chewable tablet per day for 21 days.

One tablet consists of a minimum of 200 million live Lactobacillus reuteri Gastrus. Ingredients: Bulking agent (isomalt), L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475, fully hydrogenated vegetable oil (palm), flavour enhancer (ascorbic acid), mandarin flavouring and mint flavouring. One tablet consists of a minimum of 200 million live L. reuteri Gastrus. Net weight per tablet: 700 mg.

There is no physical follow-up visit at hospital. At 21 days patients will post a faecal sample to the hospital in a pre-paid sampling/postal kit. This will mark the end of trial involvement.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

1. The feasibility of initiating studies in the secondary care setting, by identifying potential participants but study interventions carried out in the community
2. The feasibility of conducting a randomised controlled trial in immuno-competent adults known to be colonised with multi-resistant K pneumoniae and an assessment of recruitment and retention rates over a 12 month period

Secondary outcome measures

1. Faecal counts of multi-resistant Klebsiella pneumoniae measured using faecal sampling and culture at day 0 and day 21±2
2. Faecal counts of carbapenemase-bearing Klebsiella pneumoniae measured using faecal sampling and culture at day 0 and day 21±2

Overall trial start date

27/11/2018

Overall trial end date

17/12/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Written informed consent
2. Male or female; aged 18 years or older
3. Immunocompetent as per medical history
4. TCD-KP detected on rectal screening in the last 2 months
5. Not currently hospital inpatient (when planning starting probiotic supplementation)

All individuals will be considered for inclusion in this study regardless of age, disability, gender reassignment, marriage and civil partnership, pregnancy and maternity, race, religion and belief, sex, and sexual orientation except where the study inclusion and exclusion criteria EXPLICITLY state otherwise.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

1. Any active infection at the time of enrolment
2. Presence of or likely to develop mucositis on examination, as per medical history
3. History of Presence cardiac prostheses
4. Consumption of any marketed probiotic product in the 30 day period prior to enrolment and during the duration of the trial
5. Consumption of Over the Counter (OTC) medication or herbal remedies labelled as to improve your immunity system or “for daily immunity”
6. In receipt of systemic or intestinal antibiotic within 14 days before baseline samples to be taken
7. Receiving or intended to receive antibiotic within 30 days of 1st baseline sample
8. Current and past history of pancreatitis
9. Concurrent melaena
10. Abdominal surgery within the 3 months prior to study enrolment
11. Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy
12. Any medical condition, which in the opinion of the Investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
13. Past medical history of Severe renal dysfunction at Visit 0, defined as e GFR <30 mL/min, or end-stage renal disease requiring dialysis.
14. History of severe hepatic impairment or liver dysfunction at Visit 0, defined as total bilirubin above the ULN (excluding patients with Gilbert’s syndrome), AST or ALT >3 times the ULN or alkaline phosphatase >2.5 times the ULN
15. Known hypersensitivity to any of the components of the probiotic.
16. Pregnancy, lactation or planning pregnancy. A pregnancy test will not be required before study enrolment, however, if a woman determines that she is pregnant during the study period, she must stop the probiotic

Recruitment start date

02/09/2019

Recruitment end date

26/11/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Manchester Royal Infirmary
Manchester University NHS Foundation Trust Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Wythenshawe Hospital
Manchester University NHS Foundation Trust Southmoor Road
Manchester
M23 9LT
United Kingdom

Sponsor information

Organisation

Manchester University NHS Foundation Trust

Sponsor details

Trust Headquarters
Cobbett House
Oxford Road
Manchester
M13 9WL
United Kingdom
+44 (0)161 276 4125
lynne.webster@mft.nhs.uk

Sponsor type

Hospital/treatment centre

Website

https://mft.nhs.uk/research/

Funders

Funder type

Other

Funder name

Healthcare Infection Society

Alternative name(s)

HIS

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

1. Peer-reviewed scientific journals
2. Conference presentation
3. The researchers do not wish to make the protocol available at this point, but will likely do so at the conclusion of the study when they publish

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date

Intention to publish date

01/06/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes