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
Protocol serial number	PHGX09A
Sponsor	Laboratory of the Government Chemist (LGC) on behalf of the UK Department of Health
Funder	Department of Health, Pharmacogenetics Research Programme PHGX09A, UK

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

Centre for Integrated Genomic Medical Research (CIGMR)
Stopford Building
Oxford Road
The University of Manchester
Manchester
M13 9PL
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
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
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Azathioprine
Primary outcome measure(s)	Neutropaenia (defined as a neutrophil count falling below 1 x 10^9/l) in the first four months of maintenance AZA treatment.
Key secondary outcome measure(s)	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).
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	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

United Kingdom
England

Study participating centre

Centre for Integrated Genomic Medical Research (CIGMR)

Manchester
M13 9PL
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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