A prospective randomised controlled trial of thiopurine methyltransferase (TPMT) genotyping in the management of patients, prior to commencement of azathioprine
| ISRCTN | ISRCTN30748308 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN30748308 |
| Secondary identifying numbers | PHGX09A |
- Submission date
- 07/03/2005
- Registration date
- 29/06/2005
- Last edited
- 04/08/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof WER Ollier
Scientific
Scientific
Centre for Integrated Genomic Medical Research (CIGMR)
Stopford Building
Oxford Road
The University of Manchester
Manchester
M13 9PL
United Kingdom
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study acronym | TARGET (TPMT: Azathioprine Response to Genotyping and Enzyme Testing) |
| Study objectives | This study uses a prospective randomised controlled trial (PRCT) design, to assess the clinical utility and relative cost effectiveness of a pharmacogenetic test (PGx) (TPMT: Thiopurine Methyltransferase) for use in patients treated with azathioprine (AZA) for inflammatory conditions. The objectives are to: a. Assess the relative clinical outcomes of using a PGx test in patients eligible for treatment with AZA as part of their routine care compared with standard care b. Assess the relative impact on health-related quality of life of using a PGx test in patients eligible for treatment with AZA as part of their routine care compared with standard care c. Identify the relative amounts of resource use and associated costs incurred by the NHS during the clinical consultation, associated laboratory tests and subsequent treatments in patients eligible for treatment with AZA as part of their routine care compared with standard care d. Use clinical, cost and quality of life data collected in this study to assess the relative cost effectiveness (value for money) of a PGx test compared to standard care in treatment with AZA e. Value service providers and users preferences for the outcome and process components of a PGx test The project comprises a number of discrete studies that will each be used to address the stated research questions: 1. A national survey of prescribing practice in AZA 2. A PRCT of the clinical and relative cost effectiveness of a PGx test compared to standard care for a patient population who are eligible for treatment with AZA 3. A preference study to identify service users and providers views about introducing a PGx test 4. A phenotyping study investigating genotype-phenotype interactions and the potential role of other genes in the disease/treatment pathways 5. A study that examines the influences of various genetic variants on response to other immunosuppressive drugs including steroids and the new biologic agents |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Inflammatory bowel disease, arthritides and atopic dermatitis |
| Intervention | Intervention: Genotyping for TPMT + standard care Control: Standard care with no TMPT genotyping |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Azathioprine |
| Primary outcome measure | Neutropaenia (defined as a neutrophil count falling below 1 x 10^9/l) in the first four months of maintenance AZA treatment. |
| Secondary outcome measures | 1. Reduction of AZA dose or stopping AZA because of intolerance in the first four months of maintenance AZA treatment. 2. Moderate neutropaenia (defined as a neutrophil count falling below 1.5 x 10^9/l) in the first four months of maintenance AZA treatment. 3. No reduction in drug efficacy in each of the three conditions (IBD, arthritides and atopic dermatitis) under study because of changes in the dose prescribed. This will be measured using standard tools to value improvement in clinical status for each condition, which will be collected on day 0 and month 4. 4. Patients who stop AZA therapy because of non-haematological toxicity within 4 months (e.g. nausea, hepatotoxicity, pancreatitis). This will be measured by recording all side effects attributed to AZA throughout the study period. 5. Health related quality of life status. A standardised generic health status measurement tool, the EQ-5D (EuroQoL), will be used to assess the impact on health related quality of life. The EQ-5D (EuroQoL) will be completed by all study participants on two occasions (day 0 and month 4). |
| Overall study start date | 01/10/2005 |
| Completion date | 31/12/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 1000 |
| Key inclusion criteria | Adult patients assessed as eligible for treatment with oral azathioprine in the management of selected conditions in gastroenterology, rheumatology or dermatology. Selected conditions in gastroenterology (ulcerative colitis, Crohn's disease, indeterminate colitis, autoimmune hepatitis), rheumatology (rheumatoid arthritis, systemic lupus erythematosus, vasculitis, Wegener's granulomatosis, dermatomyositis) or dermatology (atopic dermatitis, contact dermatitis, chronic actinic dermatitis). |
| Key exclusion criteria | Not provided at time of registration |
| Date of first enrolment | 01/10/2005 |
| Date of final enrolment | 31/12/2007 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Centre for Integrated Genomic Medical Research (CIGMR)
Manchester
M13 9PL
United Kingdom
M13 9PL
United Kingdom
Sponsor information
Laboratory of the Government Chemist (LGC) on behalf of the UK Department of Health
Government
Government
LGC
Queen's Road
Teddington
TW11 0LY
United Kingdom
"ROR" |
https://ror.org/03sbpja79 |
|---|
Funders
Funder type
Government
Department of Health, Pharmacogenetics Research Programme PHGX09A, UK
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/06/2011 | Yes | No |
