ANZCTR - Registration

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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]

nil

Universal Trial Number (UTN)

Trial acronym

PROxIMO

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Ulcerative Colitis

Crohn's Disease

Condition category

Condition code

Oral and Gastrointestinal

Crohn's disease

Oral and Gastrointestinal

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]

Treatment: Drugs

Intervention code [2]

Treatment: Devices

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

Change in quality of life (QOL) measurement using the validated Inflammatory Bowel Disease Questionnaire (IBDQ)

Timepoint [1]

Baseline, six, and 12-months post commencement of the intervention

Secondary outcome [2]

Percentage of patients remaining in remission (ie no active disease), measured by fecal calprotectin testing

Timepoint [2]

6 and 12 months post-commencement of the intervention

Secondary outcome [3]

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]

Every 6-8 weeks depending on patient's infliximab schedule, for 12-months post commencement of the intervention

Secondary outcome [4]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Alfred - Prahran

Recruitment postcode(s) [1]

3004 - Prahran

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Alfred Hospital Pharmacy Department

Address [1]

55 Commercial Road
Melbourne Victoria 3004

Country [1]

Australia

Funding source category [2]

Commercial sector/Industry

Name [2]

Buhlmann Laboratories AG

Address [2]

Baselstr. 55
CH-4124 Schonenbuch

Country [2]

Switzerland

Primary sponsor type

Hospital

Name

Alfred Health Pharmacy Department

Address

55 Commercial Road
Melbourne Victoria 3004

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Human Research Ethics Committee

Ethics committee address [1]

55 Commercial Road
Melbourne Victoria 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/02/2016

Approval date [1]

16/03/2016

Ethics approval number [1]

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

Prof Michael Dooley

Address

Pharmacy Department
Alfred Hospital
55 Commercial Road
Melbourne 3004 Victoria

Country

Australia

Phone

+61390762061

Fax

m.dooley@alfred.org.au

Contact person for public queries

Name

Clarissa Rentsch

Address

Pharmacy Department
Alfred Hospital
55 Commercial Road
Melbourne 3004 Victoria

Country

Australia

Phone

+61390762061

Fax

c.rentsch@alfred.org.au

Contact person for scientific queries

Name

Clarissa Rentsch

Address

Pharmacy Department
Alfred Hospital
55 Commercial Road
Melbourne 3004 Victoria

Country

Australia

Phone

+61390732061

Fax

c.rentsch@alfred.org.au

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

Type	Is Peer Reviewed?	Citations or Other Details
Plain language summary	No	The rapid test is accurate and its application in ... [More Details]
Conference abstract	No	Rentsch C, Sparrow M, Ward M, Friedman A, Taylor K... [More Details]
Conference abstract	No	Rentsch C, Sparrow M, Ward M, Friedman A, Taylor K... [More Details]

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