Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612001107819
Ethics application status
Approved
Date submitted
15/10/2012
Date registered
17/10/2012
Date last updated
17/10/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Febuxostat-thiopurine combination therapy in patients with moderately severe inflammatory bowel disease
Scientific title
Febuxostat-thiopurine combination therapy in patients with moderately severe inflammatory bowel disease (IBD): a pilot study of a novel drug combination that may influence thiopurine bioavailability
Secondary ID [1] 281397 0
Nil
Universal Trial Number (UTN)
U1111-1135-8358
Trial acronym
Febuxostat-thiopurine bioavailability trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
inflammatory bowel disease 287634 0
Condition category
Condition code
Oral and Gastrointestinal 287968 287968 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To use the combination of febuxostat and 6-mercaptopurine over 4 weeks. 40mg febuxostat will be taken orally once daily together with 6-mercaptopurine at a dose of 1/3 that based on thiopurine methyl transferase activity (TPMT) prediction. (The rule of thumb of 1/3 dosing is based on our published experience with the other xanthine oxidase inhibitor (allopurinol)-thiopurine combination
Intervention code [1] 285876 0
Treatment: Drugs
Comparator / control treatment
not applicable - will be monitoring drug levels with the combination treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288179 0
therapeutic drug monitoring of drug efficacy using concurrent monitoring of total 6-thioguanine (6TG) methyl 6-mercaptopurine (me6MMP) in red blood cells (method of Dervieux and Bouleau)
together with the ratio of mean red blood cell volume : white blood cell count in peripheral venous blood
Timepoint [1] 288179 0
1,2,4 weeks
Secondary outcome [1] 299554 0
drug combination efficacy by -

clinical measures of disease activity: Harvey Bradshaw for Crohn's or Simple severity of colitis index for ulcerative colitis as appropriate, together with C-reactive protein and requirement for and dose of steroid
Timepoint [1] 299554 0
1,2,4 weeks

Eligibility
Key inclusion criteria
i) moderately severe IBD
ii) patients who accumulate methylated thiopurine metabolites
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i) allergic reaction to 6-mercaptopurine
ii) not so severe as to fit PBS criteria for anti-TNFa treatments
iii) TPMT < 0.3

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)
Single site, pilot study

STUDY SETTING/LOCATION
Single site, Mater Adults Hospital, Gastroenterology department

STUDY DURATION
One year from patient recruitment to write up

STUDY POPULATION
Patients with moderately severe IBD
Recruitment Process
Patients will be recruited at their routine clinic visit.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
nil
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2012
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
6
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 286154 0
Self funded/Unfunded
Name [1] 286154 0
Country [1] 286154 0
Australia
Primary sponsor type
Individual
Name
Prof Tim Florin
Address
Dept Gastroenterology, Mater Health Services, Raymond Terrace, South Brisbane, QLD 4101
Country
Australia
Secondary sponsor category [1] 284962 0
None
Name [1] 284962 0
Address [1] 284962 0
Country [1] 284962 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288212 0
Mater Health Services HREC
Ethics committee address [1] 288212 0
Quarters Building, Raymond Terrace, South Brisbane, QLD 4101
Ethics committee country [1] 288212 0
Australia
Date submitted for ethics approval [1] 288212 0
Approval date [1] 288212 0
04/10/2012
Ethics approval number [1] 288212 0
1926A

Summary
Brief summary
1. BACKGROUND
Febuxostat is a novel xanthine oxidase inhibitor licensed in USA, Europe and Japan for treatment of gout and other hyperuricemic disorders. There has been no attempt to license it in Australia because the market is considered too small. In Australia, the only xanthine oxidase inhibitor on the market is allopurinol. Allopurinol is an analogue of xanthine, which competitively binds xanthine oxidase. Febuxostat is not a xanthine analogue and so works by a different mechanism to competitively inhibit xanthine oxidase.
The cornerstone of treatment of patients with moderately severe IBD is thiopurine therapy. Thiopurines are cytotoxic and immunosuppressive therapies originally designed for treatment of acute childhood leukemias and for organ transplantation. Patients have regular monitoring of treatment response as well as blood tests (FBC = full blood count) to ensure that there is no over-immunosuppression and that there is no excessive build-up of methylated metabolites which are hepatotoxic (therapeutic drug monitoring of thiopurine metabolites).
Prof Florin and others have pioneered the combination of allopurinol – thiopurine co-therapy in IBD. The advantages of this therapy are that there the thiopurine requires a considerably lower dose (about 1/3 normal dose) to achieve a beneficial treatment outcome and there are less of its toxic methylated metabolites. Currently, there is debate about why allopurinol can result in less methylated metabolites because allopurinol has no known action on methylating enzymes. Some people think that a metabolite of allopurinol inhibits the methylation enzyme but this has not been proven.
Allopurinol is generally well tolerated but there are known severe adverse drug reactions including hepatitis, fever, severe skin rash, eosinophilia and renal failure which occurs especially in Asian populations. Febuxostat is a good alternative therapy to allopurinol, but its therapeutic action when combined with thiopurines is unknown. We wish to investigate whether febuxostat – thiopurine co-therapy also works for IBD patients.

2. AIM(S) OF STUDY
A pilot experiment with highly motivated patients who accumulate increased methylated metabolites on thiopurine monotreatment.

3 HYPOTHESES
3.1 The combination of thiopurine – febuxostat will allow us to use less thiopurine to effect immunosuppressive and therapeutic success.
3.2 Febuxostat will cause a reduction in methylated metabolites of thiopurines.
Trial website
nil
Trial related presentations / publications
nil
Public notes

Contacts
Principal investigator
Name 34833 0
Address 34833 0
Country 34833 0
Phone 34833 0
Fax 34833 0
Email 34833 0
Contact person for public queries
Name 18080 0
Prof Tim Florin
Address 18080 0
Mater Health Services, Raymond Terrace, South Brisbane, QLD 4101
Country 18080 0
Australia
Phone 18080 0
+61412764379
Fax 18080 0
+61731631548
Email 18080 0
[email protected]
Contact person for scientific queries
Name 9008 0
Tim Florin
Address 9008 0
Mater Health Services
Qld 4101
Country 9008 0
Australia
Phone 9008 0
+61412764379
Fax 9008 0
+61412764379
Email 9008 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
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.