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Trial registered on ANZCTR


Registration number
ACTRN12622001310752
Ethics application status
Approved
Date submitted
19/09/2022
Date registered
11/10/2022
Date last updated
11/10/2022
Date data sharing statement initially provided
11/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
ISOMETRIC CD (Efficacy of subcutaneous infliximab maintenance therapy in perianal Crohn’s disease.
Scientific title
ISOMETRIC CD (Efficacy of subcutaneous infliximab maintenance therapy in perianal Crohn’s disease
Secondary ID [1] 307566 0
NIl Known
Universal Trial Number (UTN)
N/A
Trial acronym
ISOMETRIC CD
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
perianal Crohn’s disease 327014 0
Condition category
Condition code
Oral and Gastrointestinal 324192 324192 0 0
Crohn's disease
Oral and Gastrointestinal 324193 324193 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
SWITCH IV INFLIXIMAB TO SUB CUTANEOUS INFLIXIMAB.
Eligible patients for the study with be consented. Eligible patients are those with perianal fistulising Crohn’s disease who have been on a stable infliximab dose for three months. Patients will change to subcutaneous infliximab from intravenous infliximab. Standard subcutaneous dosing will be 120mg fortnightly. First dose will be administered 8 weeks after their last infliximab infusion. This would correspond as to when they would have received another infliximab infusion.
Patients will get infliximab serum trough drug levels at 3, 6 and 12 months to assess if levels are therapeutic (considered standard of care). (Serum drug levels are a blood test to measure how much Infliximab is in the blood.) Infliximab can be increased/decreased at the clinician’s discretion. Clinicians may adjust infliximab dosing based on clinical, radiological, biochemical assessments of disease or infliximab trough levels at their discretion.
Infusions will occur in house at the tertiary hospital. Sub cutaneious Infliximab can be self administered by the participants or by a health care professional. This will be a choice made by the participants.
administration of Infliximab will occur for as long as required as per local hospital guidelines

.
Patients who cease subcutaneous infliximab due to treatment failure of the subcutaneous infliximab will continue care with their usual gastroenterologist. They will be assessed for clinical response, fistula healing and closure, and have blood tests, faecal calprotectin and a pelvic MRI completed. Their clinical progress and medication history will be followed-up until they reach 12 months and data on any major adverse outcomes such as Crohn's disease-related surgery, hospitalisation, and persistence of infliximab use will be collated.
Intervention code [1] 324575 0
Treatment: Drugs
Comparator / control treatment
INTRAVENEOUS INFUSION INFLIXIMAB
Control group
Active

Outcomes
Primary outcome [1] 332005 0
measure the rate of treatment persistence at 52 weeks follow up in patients with Perianal Fistulising Crohn's Disease (pfCD) who are switched from maintenance intranvenous infliximab to subcutaneous infliximab.
1) yes
2) see above
3) data will be collected in RedCAP at study visits. Responses to Questionaires will be collected in Redcap
Timepoint [1] 332005 0
52 WEEKS from commencement of Infliximab
Secondary outcome [1] 411882 0
1) To determine patient-reported outcomes of the patients with cpfCD at baseline, 6 and 12 months with the Crohn’s Anal Fistula Quality of Life Scale26 and compare over time
Timepoint [1] 411882 0
AT 6 AND 12 MONTHS
Baseline not relevant

Eligibility
Key inclusion criteria
Adult patients, male or female aged 18 years to 75 years old
Patients with pfCD who have or have had single or multiple externally draining perianal fistulas who are eligible for maintenance therapy infliximab as per Pharmaceutical Benefits Scheme criteria. This incorporates patients with confirmed pfCD treated by a gastroenterologist or a consultant physician in either internal or general medicine specialising in gastroenterology; with Crohn's disease confirmed by standard clinical, endoscopic or radiological assessment; and who have/had an externally draining perianal fistula.
Patients on a stable dose of infliximab for 3 months (between 5mg/kg and 10mg/kg every 8 weeks (as maximum dosing)).
Patients with pfCD and concurrent luminal disease or patients with isolated perianal fistulising Crohn's disease without luminal disease. Isolated pfCD will be defined as perianal fistulas with typical histological features of Crohn's disease
Patients with or without a seton in situ
Patients with concurrent or previous therapies for Crohn's disease including 5-aminosalicylic acids, thiopurines, methotrexate and corticosteroids
Patients who have previously trialled non-anti-TNF biologic or small molecule agents
Patients without presence of an abscess or perianal fistula on physical exam
Patients with rectovaginal, rectovesical, and/or enteroenteric fistulas with at least one separate perianal (anorectal) fistula with active external draining or that was previously draining/present
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who have commenced infliximab within the last 3 months
Patients who have undergone escalation of infliximab within the last 3 months
Patients on more than 20mg of prednisolone
Patients planned to undergo faecal stream diversion surgery in the next 3 months
Uncontrolled perianal sepsis, as determined by colorectal surgeon review
Usual Pharmaceutical Benefits Scheme exclusions to infliximab therapy including active systemic infections, untreated latent tuberculosis, malignancy in the last 5 years with the exception of non-melanoma skin cancer, untreated Clostridium difficile infection, moderate to severe heart failure, known systemic lupus erythematosus or connective tissue disorder, and autoimmune demyelinating conditions

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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
Descriptive statistics will be used to analyse demographic, disease and treatment characteristics. Categorical variables will be summarized as frequency (%) and continuous variables as mean and standard deviation (SD) for normally distributed data or median and range or inter-quartile range (IQR) for non-normally distributed data. Mann-Whitney U test will be used to compare differences across medians for non-normally distributed data. Kaplan Meier survival analysis will be used to generate treatment persistence. We will use repeated measures analysis of variance (ANOVA) to analyse trends in disease activity indices and to assess changes in Faecal calprotectin, CRP and serum infliximab levels with Bonferroni correction for multiple analyses and Scheffe test for post-hoc analyses. Only patients with complete data at each time point will be included for repeated measures ANOVA. A Wilcoxon signed rank test will be used to assess change in disease activity indices and biomarkers from baseline to last follow-up. Descriptive methods will be used to analyse reasons for treatment discontinuation and surgery. We aim to perform a logistic regression to assess variables associated with treatment persistence and a linear regression analysis to assess variables associated with serum infliximab levels after switching. We will use the mean serum infliximab levels of measurements obtained at 3, 6 and 12 months. The patient preference questionnaire will be analysed with an intention-to-treat level. Variables were chosen on the basis of clinical relevance and previously published factors associated with serum infliximab levels.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/10/2022
Actual
Date of last participant enrolment
Anticipated
31/10/2023
Actual
Date of last data collection
Anticipated
29/02/2024
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 22819 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment postcode(s) [1] 38108 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 311840 0
Other Collaborative groups
Name [1] 311840 0
Inflammatory Bowel Disease Unit. Gastroenterology Department Royal Melbourne Hospital
Country [1] 311840 0
Australia
Primary sponsor type
Hospital
Name
Royal Melbourne Hospital
Address
300 GRATTAN STREET PARKVILLE 3052 VIC AUSTRALIA
Country
Australia
Secondary sponsor category [1] 313316 0
Name [1] 313316 0
N/A
Address [1] 313316 0
N/A
Country [1] 313316 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311282 0
ROYAL MELBOURNE HOSPITAL Human Research Ethics Committee
Ethics committee address [1] 311282 0
Ethics committee country [1] 311282 0
Australia
Date submitted for ethics approval [1] 311282 0
29/06/2022
Approval date [1] 311282 0
14/09/2022
Ethics approval number [1] 311282 0
n/a

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

Contacts
Principal investigator
Name 120562 0
A/Prof Britt Christensen
Address 120562 0
Gastroenterology Department
Royal Melbourne Hospital
300 Grattan Street Parkville 3052 VIC
Country 120562 0
Australia
Phone 120562 0
+61 3 93427172
Fax 120562 0
Email 120562 0
[email protected]
Contact person for public queries
Name 120563 0
ALEX ELFORD
Address 120563 0
Gastroenterology Department, Royal Melbourne Hospital, 300 Grattan St Parkville 3052 VIC
Country 120563 0
Australia
Phone 120563 0
+61 3 9342 7000
Fax 120563 0
Email 120563 0
[email protected]
Contact person for scientific queries
Name 120564 0
ALEX ELFORD
Address 120564 0
Gastroenterology Department, Royal Melbourne Hospital, 300 Grattan St Parkville 3052 VIC
Country 120564 0
Australia
Phone 120564 0
+61 3 9342 7000
Fax 120564 0
Email 120564 0
[email protected]

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


What supporting documents are/will be available?

No Supporting Document Provided



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.