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Trial registered on ANZCTR


Registration number
ACTRN12617000561381
Ethics application status
Approved
Date submitted
10/04/2017
Date registered
21/04/2017
Date last updated
8/10/2019
Date data sharing statement initially provided
29/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Gastrointestinal eradication of multi-resistant gram negative bacteria by faecal microbiota transplantation (FMT)
Scientific title
Gastrointestinal eradication of multi-resistant gram negative bacteria by faecal microbiota transplantation (FMT)
Secondary ID [1] 290575 0
None
Universal Trial Number (UTN)
U1111-1190-0776
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
infection 301030 0
Condition category
Condition code
Infection 300823 300823 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the intervention group will receive faecal microbiota transplantation (FMT) via enema from donor stool. Participants will receive enemas weekly for three weeks in total.

Faecal transplants will contain stool from healthy donors who are rigorously screened for infection or co-morbid conditions prior to donation. The stool donations are processed by the principal investigator who is a physician (FRACP) and clinical microbiologist (FRCPA). The stool is transferred to an anaerobic biosafety chamber within 2 hours of passage to preserve the microbes and blended with sterile normal saline and pharmaceutical grade glycerol within the chamber. The final composition of the faecal transplant contians 25% stool, 65% saline and 10% glycerol. Individual transplants are frozen at -80C . The transplants from a minimum of 3 to a maximum of 10 donors will subsequently be pooled prior to the transplants being administered so that every participant in the trial receives the same FMT.

Each transplant consists of a 67mL enema. These will be administered by one of the study investigators all of whom are trained physicians. The procedure should take no more than 30 minutes.
Intervention code [1] 296441 0
Treatment: Other
Comparator / control treatment
Participants in the control group will be given their own stool in the enema, this will serve as a placebo stool transplant.
Control group
Placebo

Outcomes
Primary outcome [1] 300245 0
Relative abundance of Gram negative pathogenic organisms in the stool microbial community as assessed by next generation sequencing
Timepoint [1] 300245 0
1 year post FMT procedure
Secondary outcome [1] 329488 0
Number of episodes of infection, as assessed by positive culture of clinical specimen (not faeces) for resistant Gram negative organism with same resistance mechanism as detected prior to FMT, in addition to requirement for treatment of this infection with antibiotics.
Timepoint [1] 329488 0
1 year post FMT procedure
Secondary outcome [2] 333755 0
Carriage of resistance genes in gut microbiota, as assessed by high throughput DNA sequencing and meta-genomic analysis.
Timepoint [2] 333755 0
1 year post FMT procedure
Secondary outcome [3] 333756 0
Observation of changes to gut microbiota occurring post-FMT using high throughput DNA sequencing and meta-genomic analysis.
Timepoint [3] 333756 0
1 year post FMT procedure

Eligibility
Key inclusion criteria
1. Patients with refractory or recurrent infection–defined as at least 3 episodes of infection requiring at least 3 episodes of antibiotic therapy in preceding 24 months.
2. These infections were caused by a Gram negative bacterium which has acquired clinically important antibiotic resistance. This is defined as reported resistance to one or more of the following antibiotics: meropenem, ceftriaxone, cefepime, ceftazidime, cefalexin, amoxicillin-clavulanate, piperacillin-tazobactam, ciprofloxacin, gentamicin or trimethoprim.
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active gastrointestinal infection
Ie bacterial or viral infection causing symptoms of diarrhoea
(colonisation with MRGNB is not considered to be an infection)
2. Pregnancy
3. Current use of antibiotics*
4. Cognitive impairment
5. Perianal inflammation
6. Life expectancy < 1 year
7. Neutropaenia <0.5 X109/L
8. Severe IgE mediated food allergy : urticaria or anaphylaxis
9. At risk of peritonitis: including patients with ascities or peritoneal dialysis
*The use of trimethoprim-sulfamethoxazole is allowed when used for prophylaxis against Pneumocystis infection in immunosuppressed individuals.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size for the study was calculated using a binary outcome superiority trial power calculation. From animal study data, we expect at least an approximately 80% success in the intervention group and a 20% elimination rate in the placebo group. Significance level (alpha) was 0.05 with a power of 90%. This yielded a sample size required per group of 10 with a total sample size of 20.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 7740 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 7741 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [3] 7742 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 15670 0
5000 - Adelaide
Recruitment postcode(s) [2] 15671 0
5011 - Woodville
Recruitment postcode(s) [3] 15672 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 296057 0
Hospital
Name [1] 296057 0
Central Adelaide Local Health Network
Address [1] 296057 0
The Queen Elizabeth Hospital
11 Woodville Rd
Woodville SA 5011
Country [1] 296057 0
Australia
Funding source category [2] 296058 0
Other
Name [2] 296058 0
SA Health and Medical Research Institute
Address [2] 296058 0
North Terrace
Adelaide SA
5000
Country [2] 296058 0
Australia
Primary sponsor type
Hospital
Name
The Queen Elizabeth Hospital
Address
The Queen Elizabeth Hospital
11 Woodville Rd
South Woodville SA 5011
Country
Australia
Secondary sponsor category [1] 294947 0
None
Name [1] 294947 0
Address [1] 294947 0
Country [1] 294947 0
Other collaborator category [1] 279511 0
Other
Name [1] 279511 0
SA Health and Medical Research Institute
Address [1] 279511 0
North Terrace
Adelaide SA 5000
Country [1] 279511 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297405 0
Central Adelaide local Health Network Ethics Committee
Ethics committee address [1] 297405 0
The Queen Elizabeth Hospital
Basil Hetzel Institute DX465101
28 Woodville Road
Woodville South SA 5011
Ethics committee country [1] 297405 0
Australia
Date submitted for ethics approval [1] 297405 0
29/01/2016
Approval date [1] 297405 0
13/04/2016
Ethics approval number [1] 297405 0
HREC/16/TQEH/32

Summary
Brief summary
The emergence of bacteria or germs that have become resistant to most antibiotic treatments is an urgent public health problem. Often called “superbugs”, these germs have the ability to resist treatment with almost all antibiotics and can infect hospitalized as well as healthy people in the community. Superbugs transform previously easily treated minor infections into life-threatening conditions with very few treatment options. So far efforts to reduce superbug spread in our hospitals have failed to halt the global spread of these organisms. Nor are there new antibiotics in production to deal with this problem. New innovative approaches are needed to deal with this emerging threat.

The faecal microbiota transplant, also called FMT, is a procedure where stool is collected from healthy donors and delivered to the gut of the recipient. This is done with the goal of the healthy bacteria from the donor replacing the harmful bacteria in the recipient. The FMT procedure is already proven safe and effective in treating patients with another type of bacterial gut infection called Clostridium difficile. FMT has also been shown in animal studies and human cases to eliminate gut carriage of certain superbugs called multi-resistant gram negative bacteria. The elimination of gut carriage would both prevent superbug infections developing in the individual and also prevent the spread of these organisms to other persons.

In order to address this growing problem we have designed a study to test the effectiveness of FMT in people who have suffered from recurrent infections with a type of superbug. The goals of this study are to determine if FMT can result in clearance of superbug bacteria from the stool and to observe the effect of FMT on rates of recurrent infections in study participants. In collaboration with South Australian experts in this field the stool will be analysed to determine how FMT affects the range of germs in the gut and their ability to become resistant to antibiotics.

If successful this study will represent a major scientific advance in our ability to prevent superbug infection and spread. It will open up new treatment possibilities for patients who suffer from superbug infections and benefit the community at large by giving us a new tool to stop the spread of superbugs to others.
Trial website
NA
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69742 0
Dr Lito Papanicolas
Address 69742 0
The Queen Elizabeth Hospital
Woodville Road
Woodville SA 5011
Country 69742 0
Australia
Phone 69742 0
+61-88204-7616
Fax 69742 0
Email 69742 0
lito.papanicolas@sa.gov.au
Contact person for public queries
Name 69743 0
Dr Lito Papanicolas
Address 69743 0
The Queen Elizabeth Hospital
Woodville Road
Woodville SA 5011
Country 69743 0
Australia
Phone 69743 0
+61-88204-7616
Fax 69743 0
Email 69743 0
lito.papanicolas@sa.gov.au
Contact person for scientific queries
Name 69744 0
Dr Lito Papanicolas
Address 69744 0
The Queen Elizabeth Hospital
Woodville Road
Woodville SA 5011
Country 69744 0
Australia
Phone 69744 0
+61-88204-7616
Fax 69744 0
Email 69744 0
lito.papanicolas@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All data underlying published results after de-identification
When will data be available (start and end dates)?
From 3 months post-publication to 5 years post publication
Available to whom?
Researchers who submit a methodologically sound proposal
Available for what types of analyses?
To achieve the aims of proposal
How or where can data be obtained?
Proposals should be directed to lito.papanicolas@sa.gov.au
To gain access data requestors will need to sign a data sharing agreement to access data.
The link to the data is to be advised.
What supporting documents are/will be available?
Study protocol
Informed consent form
How or where can supporting documents be obtained?
Type [1] 2 0
Study protocol
Citation [1] 2 0
Link [1] 2 0
Email [1] 2 0
Other [1] 2 0
Type [2] 3 0
Informed consent form
Citation [2] 3 0
Link [2] 3 0
Email [2] 3 0
Other [2] 3 0
Summary results
No Results