Condition category
Not Applicable
Date applied
07/03/2005
Date assigned
29/06/2005
Last edited
04/08/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof WER Ollier

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PHGX09A

Study information

Scientific title

Acronym

TARGET (TPMT: Azathioprine Response to Genotyping and Enzyme Testing)

Study hypothesis

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

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

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 names

Azathioprine

Primary outcome measures

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 trial start date

01/10/2005

Overall trial end date

31/12/2007

Reason abandoned

Eligibility

Participant 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).

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1000

Participant exclusion criteria

Not provided at time of registration

Recruitment start date

01/10/2005

Recruitment end date

31/12/2007

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Centre for Integrated Genomic Medical Research (CIGMR)
Manchester
M13 9PL
United Kingdom

Sponsor information

Organisation

Laboratory of the Government Chemist (LGC) on behalf of the UK Department of Health

Sponsor details

LGC
Queen's Road
Teddington
TW11 0LY
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

Department of Health, Pharmacogenetics Research Programme PHGX09A, UK

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21692613

Publication citations

  1. Results

    Newman WG, Payne K, Tricker K, Roberts SA, Fargher E, Pushpakom S, Alder JE, Sidgwick GP, Payne D, Elliott RA, Heise M, Elles R, Ramsden SC, Andrews J, Houston JB, Qasim F, Shaffer J, Griffiths CE, Ray DW, Bruce I, Ollier WE, , A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study., Pharmacogenomics, 2011, 12, 6, 815-826, doi: 10.2217/pgs.11.32.

Additional files

Editorial Notes