The objective of this project is to find out if TPMT genotyping prior to thiopurine use is cost-effective in patients with inflammatory bowel disease (IBD) in need of immune suppression.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Outcome measures are occurrence of ADRs, clinical outcome after 5 months of
treatment, quality of life and treatment costs.
Secondary outcome
In a second phase, after inclusion of all patients and completion of the
cost-effectiveness study the DNA and phenotype data will be used for
exploratory analyses of other genes influencing treatment response.
Background summary
Pharmacogenetics aims at providing optimized drug treatment to patients by
maximizingefficacy and minimizing adverse drug reactions (ADRs) based on
genetic testing. The best-established example of a pharmacogenetic test is
genotyping of thiopurine S-methyltransferase (TPMT) in the treatment of
patients with immunosuppressive thiopurines. The frequency of ADRs (15-50%)
including life-threatening myelosuppression necessitates regular monitoring of
organ function and blood counts in thiopurine users. Genetic variants of TPMT
explain part of the bone marrow suppressions.
Study objective
The objective of this project is to find out if TPMT genotyping prior to
thiopurine use is cost-effective in patients with inflammatory bowel disease
(IBD) in need of immune suppression.
Study design
We propose to carry out a prospective randomized controlled trial (RCT)
investigating 1000 patients treated with thiopurines.The project will be
carried out in 3 years, 29 months are planned for patient inclusion, data
analysis and reporting of results will take place from month 25 to 36.
Intervention
Following randomization, 500 patients will be genotyped prior to treatment with
the clinician receiving advice on thiopurine dosing; an equal number will
receive standard treatment.
Study burden and risks
The patients will undergo an extra venapuncture, carried out by experienced
personnel, which is generally a low risk procedure. They will have to use a
diary for disease outcome evaluation for 1 week, keep track of their
expenditures with regard to disease treatment and fill out a number of
questionnaires. Furthermore, an effect on treatment outcome is possible in the
intervention group, that can be started on a lower dose of thiopurine according
to genotype.
A possible benefit of participation will be observed in the intervention group,
in which patients can be started on a lower dose of thiopurine according to
genotype, preventing myelotoxicity.
If the study shows cost-effectiveness of the pharmacogenetic test without
effect on treatment outcome, the genetic test will become available for all
future patients starting thiopurine treatment and will help prevent part of the
myelotoxicity.
Laan van Oost Indie 334
2593 CE Den Haag
Nederland
Laan van Oost Indie 334
2593 CE Den Haag
Nederland
Listed location countries
Age
Inclusion criteria
· Age 18 or older
· Diagnosis of a form of IBD
· Patient is started on azathioprine treatment
· Patient giving informed consent
Exclusion criteria
· Previous treatment with azathioprine
· Co-prescription of allopurinol (this treatment blocks xanthine oxidase, an enzyme
important for azathioprine metabolism)
· Baseline leukocyte count less then 3x10^9 per litre
· Reduced baseline liver function
· Reduced renal function at baseline
· Use of TPMT phenotype test to guide prescription
· Pregnancy or breastfeeding
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL13171.091.06 |