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Trial registered on ANZCTR


Registration number
ACTRN12624000034538
Ethics application status
Approved
Date submitted
13/12/2023
Date registered
16/01/2024
Date last updated
16/01/2024
Date data sharing statement initially provided
16/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Restoration of gut microbiota in Persistent Critical illness using Faecal Microbiota Transplantation (The ROCIT-FMT Trial): a pilot phase I/II trial
Scientific title
Restoration of gut microbiota in Persistent Critical illness patients using Faecal Microbiota Transplantation (The ROCIT-FMT Trial): a pilot phase I/II trial
Secondary ID [1] 310323 0
Nil
Universal Trial Number (UTN)
Trial acronym
ROCIT-FMT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent Critical Illness 332346 0
Condition category
Condition code
Infection 329056 329056 0 0
Other infectious diseases
Inflammatory and Immune System 329123 329123 0 0
Other inflammatory or immune system disorders
Respiratory 329124 329124 0 0
Other respiratory disorders / diseases
Renal and Urogenital 329125 329125 0 0
Other renal and urogenital disorders
Cardiovascular 329126 329126 0 0
Other cardiovascular diseases
Oral and Gastrointestinal 329127 329127 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Escalating doses of Australian Red Cross Lifeblood faecal microbiota transplant (FMT) product will be administered via nasogastric tube at pre-determined escalation infusion rates to participants who meet the eligibility criteria and provide informed consent. Initial dose will be 50g of FMT at a rate of 25ml/hr to initial 3 participants. The dose will then be escalated to 100g at 25ml/hr to the next 3 participants pending tolerability of the initial dose. The infusion rate will subsequently be escalated to 37.5ml/hr for the subsequent 3 participants. The final 3 participants in stage 1 will received 150g of FMT at a rate of 37.5ml/hr. Premedication with a proton pump inhibitor will be initiated at least 36 hours prior to FMT administration (i.e. 3 doses 12 hours apart to be received prior to FMT) and an anti-emetic agent will be initiated a minimum of 12 hours prior to intervention. Rectal swabs will be collected pre FMT administration (within 6 hours prior to planned administration) and at pre-determined timepoints (day 1, 5 and 7 post) after intervention by the registered bedside nursing staff.
Intervention code [1] 327615 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336861 0
i) Safety of FMT via NG administration in ICU patients with evidence of PerCI, as assessed by the incidence of grade 3-5 FMT-related adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. FMT will be considered unsafe in critically ill patients when there are definitely FMT-related SAE in >1 participant.
- data will be collected from electronic medical records
Timepoint [1] 336861 0
Baseline, Day 5, Day 7, Day 30 post FMT administration.
Secondary outcome [1] 429906 0
i) Proportion of all FMT recipients with successful engraftment, as defined by either a proportional increase of > 30% strain sharing between donor and recipient samples post FMT as compared to donor and recipient pre FMT OR an absolute strain sharing rate of > 50%.
- data will be generated from whole genome sequencing of the rectal swabs of each participants pre FMT and at the specified timepoints post FMT administration and comparison of strain sharing percentages will be made between pre and post intervention swab results.
Timepoint [1] 429906 0
Day 5 and day 7 post FMT administration.
Secondary outcome [2] 429907 0
Any change in alpha diversity (Shannon Index) between baseline samples and day 7 post FMT samples using metagenomic sequencing.
Timepoint [2] 429907 0
Day 7 post FMT administration.
Secondary outcome [3] 429908 0
Differential abundance of microbial taxa in recipients, comparing Day 0 and day 7 post FMT
Timepoint [3] 429908 0
Day 7 post FMT administration.
Secondary outcome [4] 429909 0
Change in absolute bacterial load in recipient on day 7 post FMT via metagenomic sequencing.
Timepoint [4] 429909 0
day 7 post FMT administration.
Secondary outcome [5] 429910 0
Beta diversity between recipients post-FMT and donor samples compared to recipients pre FMT and donor samples using Bray Curtis dissimilarity +/- Jaccard index
Timepoint [5] 429910 0
day 7 post FMT administration.
Secondary outcome [6] 429911 0
Identification of specific microbiota patterns associated with success of engraftment via metagenomic sequencing.
Timepoint [6] 429911 0
Day 7 post FMT administration.
Secondary outcome [7] 429912 0
Organ support free days – defined as number of days alive without vasoactive therapy, mechanical ventilation (including NIV) and RRT. Data will be assessed via electronic medical records
Timepoint [7] 429912 0
Day 30 post FMT administration.
Secondary outcome [8] 429913 0
Incidence of newly acquired transmissible infectious diseases with onset > 12 hours post FMT. Data will be assessed via electronic medical records.
Timepoint [8] 429913 0
Day 2, 5, 7, 30 post FMT administration.
Secondary outcome [9] 429914 0
Number of participants who obtain eradication of MDRO colonisation post FMT via metagenomic sequencing.
Timepoint [9] 429914 0
Day 5, 7 post FMT administration.
Secondary outcome [10] 429915 0
ICU length of stay. Data will be assessed via electronic medical records.
Timepoint [10] 429915 0
Day 30 post FMT administration.
Secondary outcome [11] 429916 0
Change in faecal calprotectin pre and on day 7 post FMT via stool testing.
Timepoint [11] 429916 0
day 7 post FMT administration.
Secondary outcome [12] 429917 0
Change in serum CRP (blood test) pre and on day 7 post FMT.
Timepoint [12] 429917 0
Day 7 post FMT administration.

Eligibility
Key inclusion criteria
i) Age 18 years or older.
ii) Inpatient in ICU for minimum of 96 hours who have an ongoing requirement for ICU at the time of enrolment
iii) Received a minimum of 24 hours of broad-spectrum antimicrobials in the week preceding enrolment and not anticipated to require ongoing broad-spectrum antibiotics within 24 hours prior to FMT
iv) Evidence of persistent organ dysfunction as defined by at least one of i) ongoing ventilatory support [high flow nasal prong oxygen, non-invasive ventilation, mechanical ventilation], ii) persistent renal dysfunction as defined by KDIGO guidelines (need for RRT or persistent Cr greater than x1.5 premorbid baseline or persistent UO less than 0.5ml/kg/hr, iii) persistent vasoactive requirement
v) Established on and tolerating enteral feeds of at least 30ml/h via nasogastric tube for a minimum of 24hours with 4 hourly residual aspirates consistently less than 300ml in the last 24 hours.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

i)Patients with established concurrent indications for FMT including C. difficile infection and inflammatory bowel disease (IBD).
ii)Subjects with compromised immune system, including:
(a) Absolute neutrophil count (ANC) of less than 0.5 x 109 cells / L within 7 days of enrolment or sustained AN less than 1 x 109 cell / L.,
(b) Subjects on active chemotherapy or monoclonal therapy targeting B or T cells, glucocorticoids > 10mg prednisolone daily or equivalent for greater than or equal to 2 weeks (with the exception of inhaled or topical glucocorticoids which are permitted), recent bone marrow transplant [within 8 weeks], uncontrolled HIV [CD4 count less than 240 cells/mm3], anti-TNF therapy.
iii) Subjects who are pregnant or lactating.
iv) Previous FMT or microbiome-based therapeutics (exception: the use of over-the-counter probiotics).
v) Subjects with severe, life-threatening food allergies
vi) Subjects with established contra-indication to PPI administration.
vii) Subjects with contraindication to both metoclopramide and domperidone use.
viii) Inability to maintain head of participants bed at greater than 30-degree angle for 4 hours post NG administration of FMT product.
ix) The treating clinical believes that trial participation is not in the best interest of the patient
x) The treating clinician believes death is inevitable AND the clinician, next-of-kin or patient are not committed to ongoing active treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This trial is a phase I/II pilot trial based primarily on assessing safety, feasibility and preliminary efficacy of FMT in this context. The goal of this study is to establish the safety and tolerability of FMT administration via NGT in a critically ill patient population and is not powered to detect any secondary endpoints with any degree of power. The small sample size may not allow for the achievement of statistical significance but the establishment of a safe and practical method of administration in this population will allow for further research into the use of FMT and related microbiome modulating therapies going forward.

The concept of engraftment will be defined as the strain sharing rates and will be anchored to the microbiome of the donor. Each individual will have a dichotomous outcome of successful engraftment defined as a change in strain sharing of >30% or an absolute strain sharing rate of >50% at day 7. In efficacy trials of FMT for CDI, a high proportion of patients were cured and demonstrated engraftment. A target of 75% engraftment has been chosen as reasonable target. Under these conditions, a total sample size of 33 participants be able to detect a proportion of successful engraftment of 75% with a margin of error of 15% with 95% confidence. Based on this as well as feasibility and resource constraints, a maximum of 40 participants will be recruited.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2024
Actual
Date of last participant enrolment
Anticipated
31/01/2025
Actual
Date of last data collection
Anticipated
2/03/2025
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 25944 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 41777 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 314529 0
Charities/Societies/Foundations
Name [1] 314529 0
Australian Red Cross Lifebood (ARCL)
Country [1] 314529 0
Australia
Primary sponsor type
Hospital
Name
South Metropolitan Health Service - Fiona Stanley Hospital
Address
11 Robin Warren Drive, Murdoch, WA 6150.
Country
Australia
Secondary sponsor category [1] 316479 0
None
Name [1] 316479 0
Address [1] 316479 0
Country [1] 316479 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313571 0
South Metropolitan Health Service HREC
Ethics committee address [1] 313571 0
Ethics committee country [1] 313571 0
Australia
Date submitted for ethics approval [1] 313571 0
31/07/2023
Approval date [1] 313571 0
30/08/2023
Ethics approval number [1] 313571 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128590 0
A/Prof Laurens Manning
Address 128590 0
Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch, Wa 6150
Country 128590 0
Australia
Phone 128590 0
+61 8 6152 2222
Fax 128590 0
Email 128590 0
laurens.manning@uwa.edu.au
Contact person for public queries
Name 128591 0
Fionnuala Murray
Address 128591 0
Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch, Wa 6150
Country 128591 0
Australia
Phone 128591 0
+61861511146
Fax 128591 0
Email 128591 0
fionnuala.murray@health.wa.gov.au
Contact person for scientific queries
Name 128592 0
Fionnuala Murray
Address 128592 0
Fiona Stanley Hospital, 11 Robin Warren Drive, Murdoch, Wa 6150
Country 128592 0
Australia
Phone 128592 0
+61861511146
Fax 128592 0
Email 128592 0
fionnuala.murray@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As yet undecided


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21187Study protocol  fionnuala.murray@health.wa.gov.au
21188Statistical analysis plan  fionnuala.murray@health.wa.gov.au
21189Clinical study report  fionnuala.murray@health.wa.gov.au
21190Ethical approval  fionnuala.murray@health.wa.gov.au


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.