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Trial registered on ANZCTR


Registration number
ACTRN12616001031459
Ethics application status
Approved
Date submitted
2/08/2016
Date registered
4/08/2016
Date last updated
29/06/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
PROxIMO: Efficacy of proactive therapeutic drug monitoring and dose adjustment of infliximab based on point of care testing for inflammatory bowel disease
Scientific title
PROxIMO: Efficacy of proactive therapeutic drug monitoring and dose adjustment of infliximab based on point of care testing for inflammatory bowel disease
Secondary ID [1] 289828 0
nil
Universal Trial Number (UTN)
Trial acronym
PROxIMO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 299754 0
Crohn's Disease 299755 0
Condition category
Condition code
Oral and Gastrointestinal 299688 299688 0 0
Crohn's disease
Oral and Gastrointestinal 299689 299689 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will be prospective adjustments of infliximab dosing based on infliximab blood levels tested using a new point of care (POC) test, Quantum Blue Infliximab Assay, manufactured by Buhlmann Laboratories and approved for use in the European Union.
Patients currently receive infliximab therapy on a 6- or 8-weekly schedule; POC testing and dose adjustments will occur 6-8 weekly according to this schedule. The intervention period will be 12 months from the commencement of the intervention.
All eligible patients will have undergone infliximab induction, and will now be on maintenance infliximab therapy; starting dose of infliximab for this study will be the patient’s current prescribed dose.
All patients receiving infliximab infusions at this institution have established peripheral access lines, and it is routine practice for blood samples to be taken before each infusion to test biochemistry, FBE and infliximab levels via ELISA assay. Patients will have an additional 10ml of blood taken from this line, at the same time as other blood tests, by the clinic nurse, which will be applied to the POC test, which produces a result within 60 minutes.
No adherence monitoring strategies are in place.

The dosing algorithm used to prospectively adjust infliximab doses is as follows:

Infliximab trough concentration and dose adjustments:
If 0-0.9ug/ml then increase by 3mg/kg
If 1-1.9ug/ml then increase by 2mg/kg
If 2-2.9ug/ml then increase by 1mg/kg
If 3-7ug/ml - therapeutic range, no action
If 7.1-9ug/ml then decrease by 1mg/kg
If >9ug/ml then decrease by 2mg/kg
Intervention code [1] 295503 0
Treatment: Drugs
Intervention code [2] 295504 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 299150 0
The percentage of patients that obtain a therapeutic (3-7ug/mL) infliximab trough concentration using an individualised mg/kg weight based dose adjustment according to an algorithm directed by a novel POC infliximab trough assay
Timepoint [1] 299150 0
Infliximab trough levels will be assessed every 6-8 weeks based on the patient's infliximab dosing schedule, for 12 months post commencement of the intervention
Secondary outcome [1] 326328 0
Change in quality of life (QOL) measurement using the validated Inflammatory Bowel Disease Questionnaire (IBDQ)
Timepoint [1] 326328 0
Baseline, six, and 12-months post commencement of the intervention
Secondary outcome [2] 326329 0
Percentage of patients remaining in remission (ie no active disease), measured by fecal calprotectin testing
Timepoint [2] 326329 0
6 and 12 months post-commencement of the intervention
Secondary outcome [3] 326330 0
Routine care involves testing blood for infliximab levels using the ELISA assay method before every infusion (ie 6-8 weekly depending on patient's infliximab scheduling). Blood for POC testing will be taken at the same time as for the ELISA assay, before every infusion 6-8 weekly.
All POC test results will be compared against ELISA assay results, and concordance between the two assessed.
Timepoint [3] 326330 0
Every 6-8 weeks depending on patient's infliximab schedule, for 12-months post commencement of the intervention
Secondary outcome [4] 326331 0
The length of time patient's infliximab blood concentration levels remain within the therapeutic range of 3-7ug/ml, assessed by POC testing every 6-8 weeks for 6-months post commencement of the intervention
Timepoint [4] 326331 0
Every 6-8 weeks (depending on patient's infliximab schedule) for 12 months post commencement of the intervention

Eligibility
Key inclusion criteria
Adults over 18 years.
Diagnosis of moderate to severe Crohn's disease or Ulcerative Colitis
Currently receiving maintenance infliximab therapy (ie have commenced infliximab therapy at least 14 weeks prior to recruitment)
Receiving their infliximab therapy and disease monitoring through Alfred Health
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable or unwilling to provide informed consent
Patients with detectable anti-drug antibodies (ADAs) and undetectable trough levels
Pregnant or breastfeeding women

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)
No control group
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
No control group
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive analysis will be conducted and continuous variables will be evaluated using student’s t-test or Mann-Whitney U test, as appropriate. Categorical data will be analysed using chi-square test or fisher’s exact test for proportions, as appropriate. A multivariate analysis will be required to adjust for potential confounders and stratification analysed according to disease type (UC or CD).
There are currently 120 patients on maintenance infliximab therapy at this institution. We will aim to recruit 80 of these patients over a 18-month period and follow-up for up to 12 months following recruitment. As a pilot study, a power calculation is not required.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
12/07/2016
Date of last participant enrolment
Anticipated
Actual
22/11/2017
Date of last data collection
Anticipated
1/10/2018
Actual
Sample size
Target
80
Accrual to date
Final
55
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6353 0
The Alfred - Prahran
Recruitment postcode(s) [1] 13899 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 294208 0
Hospital
Name [1] 294208 0
Alfred Hospital Pharmacy Department
Country [1] 294208 0
Australia
Funding source category [2] 294219 0
Commercial sector/Industry
Name [2] 294219 0
Buhlmann Laboratories AG
Country [2] 294219 0
Switzerland
Primary sponsor type
Hospital
Name
Alfred Health Pharmacy Department
Address
55 Commercial Road
Melbourne Victoria 3004
Country
Australia
Secondary sponsor category [1] 293051 0
None
Name [1] 293051 0
Address [1] 293051 0
Country [1] 293051 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295617 0
Alfred Human Research Ethics Committee
Ethics committee address [1] 295617 0
55 Commercial Road
Melbourne Victoria 3004
Ethics committee country [1] 295617 0
Australia
Date submitted for ethics approval [1] 295617 0
03/02/2016
Approval date [1] 295617 0
16/03/2016
Ethics approval number [1] 295617 0
53/16

Summary
Brief summary
Patients with inflammatory bowel disease (IBD) are prescribed medications used to treat inflammation. Infliximab is an effective intravenous therapy that is used in the treatment of Crohn’s disease and ulcerative colitis.
Conventionally, infliximab is given as an infusion every 8 weeks. The dose of infliximab is calculated according to weight and may differ between patients. Despite initially responding to infliximab, some patients will lose response over time, such that the drug no longer continues to work as well as it once did. Studies have demonstrated that patients on a maintenance treatment are more likely to continue to show positive responses to infliximab therapy when the blood level of infliximab, measured just prior to the next scheduled infusion (referred to as a ‘trough level’), is within an optimal range (referred to as ‘therapeutic range’).
Infliximab levels are measured from a blood sample. In the past we measured infliximab levels only occasionally. This is partly because the results took time to be processed and were not available on the same day.
In this project a blood test will be taken to measure the infliximab level every time patients are due for your infliximab infusion. The test to be used is able to measure the drug level within an hour at the point of care. We will then be able to modify the infliximab dose immediately, in small increments, according to the infliximab level with the aim of ensuring that infliximab levels remain within the ideal therapeutic range.
The infliximab blood test and dose modification, if needed, will occur at each visit for the duration of the study (for 12 months, or 6-7 infusions). At each visit, 10mL (about 2 teaspoons) of blood will be taken from your peripheral access line to measure the level of infliximab in your blood along with other blood tests normally conducted when you have your infusion. The information from the blood tests will be used by the researchers to adjust the infliximab dose and to validate the dosing guide.
Participants will be asked to provide faecal samples to measure faecal calprotectin, a protein that is secreted in the intestine of patients with inflammation of the gastrointestinal tract (this is a test we currently perform periodically; during this study we will do this test at the second visit and at the end of the study). Participants will be asked to complete a brief survey that assesses quality of life at the beginning and the end of the study, and to answer some short questions about their Crohn’s disease or ulcerative colitis
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67962 0
Prof Michael Dooley
Address 67962 0
Pharmacy Department
Alfred Hospital
55 Commercial Road
Melbourne 3004 Victoria
Country 67962 0
Australia
Phone 67962 0
+61390762061
Fax 67962 0
Email 67962 0
[email protected]
Contact person for public queries
Name 67963 0
Clarissa Rentsch
Address 67963 0
Pharmacy Department
Alfred Hospital
55 Commercial Road
Melbourne 3004 Victoria
Country 67963 0
Australia
Phone 67963 0
+61390762061
Fax 67963 0
Email 67963 0
[email protected]
Contact person for scientific queries
Name 67964 0
Clarissa Rentsch
Address 67964 0
Pharmacy Department
Alfred Hospital
55 Commercial Road
Melbourne 3004 Victoria
Country 67964 0
Australia
Phone 67964 0
+61390732061
Fax 67964 0
Email 67964 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
Current Study Results
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Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4027Plain language summaryNo The rapid test is accurate and its application in ... [More Details]
4621Conference abstractNo Rentsch C, Sparrow M, Ward M, Friedman A, Taylor K... [More Details]
4622Conference abstractNo Rentsch C, Sparrow M, Ward M, Friedman A, Taylor K... [More Details]

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