Condition category
Musculoskeletal Diseases
Date applied
25/09/2012
Date assigned
05/10/2012
Last edited
27/01/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Patients newly diagnosed with Rheumatoid Arthritis (autoimmune disease that causes inflammation in your joints) are treated conventionally according to National Institute for Health and Clinical Excellence (NICE) guidelines. There is no cure for Rheumatoid arthritis (RA), instead, the goal is to achieve low disease activity and ultimately disease remission. It is not currently possible to predict which drug (or drugs) will produce a favourable response in a particular patient and it is currently difficult to identify patients in clinical remission. This study aims to define predictors of clinical response and define what true remission is in patients with early RA. The plan is to use this information to develop an 'immunological toolkit' to help predict which patients will respond well to particular treatments so that patients can be treated with individualised drug combinations that are most likely to induce and sustain remission.

Who can participate?
The study will recruit 410 participants over the age of 18 within 4 weeks of diagnosis with Rheumatoid Arthritis. They will not have received disease-modifying antirheumatic drugs (DMARDs) or corticosteroid treatment for the current episode of inflammatory arthritis. In addition all subjects will be positive for Rheumatoid Factor and Anti-citrullinated protein antibody (ACPA).

What does the study involve?
Patients will receive standard treatment following national guidelines throughout the study period. The study duration will be 18 months. Patients will be assessed at months 0, 3, 6, 9, 12, 15 and 18 using standard validated questionnaires and blood tests as set out in current guidelines. Biological sampling (blood and urine) will be carried out at each assessment for the purpose of developing an 'immunological toolkit'. X-rays will be taken at 0, 12 and 18 months.

What are the possible benefits and risks of participating?
Although not of direct benefit to participants in the study, it is hoped that the information we get from this study will help improve the treatment of people with rheumatoid arthritis in the future.
As this is an observational study there are no additional risks relating to taking medication involved beyond those which you would experience in routine care. However, there is a modest risk of side effects including pain, bruising, light headedness, and, on rare occasions, infection that could arise as a consequence of having blood taken. To minimise this risk, blood will be taken by a clinical professional trained and experienced in taking blood from patients. In all we will need to take seven lots of blood samples from you, in total about 1.5 - 3 egg cups of blood on each occasion, during this study.

Where is the study run from?
The study is being managed by King's College London. Between 26 and 40 recruitment sites will be set up across England and Scotland.

When is the study starting and how long is it expected to run for?
It is anticipated that recruitment will start Sept/Oct 2012 with the study ending after four years.

Who is funding the study?
The study is funded as part of a programme grant from the Medical Research Council (MRC).

Who is the main contact?
Professor Andrew Cope
andrew.cope@kcl.ac.uk
Study Co-ordinator
kch-tr.tacera@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Prof Andrew Cope

ORCID ID

Contact details

King's College London
Academic Department of Rheumatology
School of Medicine
New Hunt's House
Guys Hospital Campus
Great Maze Pond
London
SE1 1UL
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

97747

Study information

Scientific title

The TACERA Study: a longitudinal observational study of patients with early rheumatoid arthritis

Acronym

TACERA

Study hypothesis

Our working hypothesis is that a suite of immunological assays (hereafter termed 'the immunological toolkit') can be used to accurately predict clinical responses to therapy at a molecular and cellular level. We also propose that immune-based assays can be adapted to define an immune signature associated with a state of sustained clinical remission in patients with early RA. This study protocol seeks to recruit a large cohort of patients with early RA. Biological samples will be acquired from study subjects and used to develop the immunological toolkit, through the identification of baseline biomarker signatures (prior to starting therapy), and by documenting the changes in the immune system in response to therapeutic intervention.

Several principles underpin this study:
1. RA is associated with detectable perturbations of the immune system at very early stages of disease.
2. Clinical remission is associated with a biological state that has similarities to a healthy immune system.
3. The healthy immune system is associated with a distinct immunological fingerprint defined by serum, cellular and/or molecular signatures in peripheral blood.
4. Restoration of this state of immune health may be induced with therapies that target these perturbations.

More details can be found at http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12364

Ethics approval

London - Central Research Ethics Committee, 02/05/2012, ref: 12/LO/0469
Acknowledgment of compliance with conditions received 07/06/2012

Study design

Longitudinal observational 18-month multicentre study

Primary study design

Observational

Secondary study design

Longitudinal study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not currently available in web format, please use the contact details below to request a patient information sheet

Condition

Rheumatoid arthritis

Intervention

The study is observational, meaning that we are just looking at how arthritis responds to standard therapy in patients, rather than testing the effects of new treatments. Patients who have been diagnosed with early RA, within 6 months of symptom onset, will receive treatment according to NICE guidelines. Patients will participate in the study for 18 months, attending assessments every 3 months. During these visits a detailed assessment of disease activity (including standard blood monitoring for DMARDs and TNF-inhibitors) will take place along with completion of a number of questionnaires and the provision of additional blood and urine samples for immunoanalysis.

At each study assessment the following will take place:

Patients will complete the following with the research nurse:
1. Disease Activity Score (DAS28 & extended swollen and tender joint counts 66/68, patient global assessment)
2. HAQ (Health assessment questionnaire measuring disability)
3. Lifestyle Factors Questionnaire

The following questionnaires will be completed at Baseline, 6, 12 and 18 months only:
1. SF36 (Quality of life questionnaire)
2. EQ5D (Health outcome questionnaire)
3. FACIT-F questionnaire (Functional assessment of Chronic Illness Therapy)
4. IPQ-R-RA (Illness Perception Questionnaire)
5. MAPLe-RA (Measuring Actual Patient-Led expectations)

The following will be reviewed:
1. Concomitant Diseases and medication
2. Current Medication
3. Adverse events

The following samples will be taken:
1. Blood samples for routine safety monitoring and ESR and CRP values
2. Blood and urine samples for the immunoanalysis.

X-rays of hands and feet will be taken at Baseline, 12 and 18 months.

HRUS (High Resolution Ultrasonography) will be undertaken at baseline, 6 and 12 months (an 18 month scan will be optional). This ultasound based imaging is optional and will be offered to patients at those recruiting centres that provide this service as part of routine clinical care.

Patients may also be telephoned by their Research Nurse in between study visits to check how well their disease is being controlled by their medication.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Current primary outcome measures as of 10/06/2015:
Disease remission at 6 months will be the primary outcome and this will be measured using either the long established DAS28 criterion (DAS28 score <2.6) or the Simplified Disease Activity Index (SDAI) ≤ 3.3, or the new ACR/EULAR 2010 remission criteria:
1. Swollen joint count ≤1
2. Tender joint count ≤ 1
3. CRP ≤ 1 (mg/dl)
4. Patient global ≤ 1 (on a 1 to 10 scale)

Previous primary outcome measures:
Disease remission at 6 months will be the primary outcome and this will be measured using both the long established DAS28 criterion (DAS28 score <2.6) and the new ACR/EULAR remission criteria:
1. Swollen joint count ≤1
2. Tender joint count ≤ 1
3. CRP ≤ 1 (mg/dl)
4. Patient global ≤ 1 (on a 1 to 10 scale)
5. Simplified Disease Activity Index (SDAI) ≤ 3.3

Secondary outcome measures

1. Extended (66/68) Joint Count DAS28
2. Simple Disease Activity Score (SDAI)
3. Clinical Disease Activity Score (CDAI)
4. Health Assessment Questionnaire (HAQ) scores
5. EQ5D scores
6. SF-36
7. Radiographic progression of hands and feet X-rays scored by Larsen’s or van der Heijde Sharpe Modified Scores
8. Disease remission (as defined in primary outcome measure) at 12 and 18 months
9. Immune signatures derived from the analysis of biological samples

Overall trial start date

30/09/2012

Overall trial end date

21/01/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients should fulfill either 1987 ACR or 2010 ACR/EULAR classification criteria for diagnosis of early RA
2. Positive for serum rheumatoid factor and anti-citrullinated protein autoantibodies (ACPA)
3. Within 6 months of symptom onset
4. Supervising rheumatologist considers that starting therapy with Disease-modifying antirheumatic drugs (DMARDs) is appropriate
5. At least 18 years of age
6. Able and willing to give informed consent to provide clinical data and blood samples at defined time points for the duration of the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

274 (final recruitment figure 275)

Participant exclusion criteria

1. Previous treatment with DMARDs or biologics
2. Corticosteroid treatment for the current episode of inflammatory arthritis within the last 6 months (patients with a previous episode of inflammatory arthritis treated with corticosteroids more than 6 months before screening will be permitted providing this episode was not ongoing)
3. Use of intramuscular steroid injections between the first clinic attendance (when the diagnosis of RA is made) and study entry
4. Significant co-morbidities (e.g. severe congestive heart failure, renal, hepatic, malignant disease), as judged by the supervising physician
5. Pregnant or wishing to conceive
6. Participating in trials of investigational medicinal products or devices, or other interventions (e.g. exercise) which may have an impact on the patient’s treatment, immune status or disease activity

Recruitment start date

05/02/2013

Recruitment end date

10/07/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Birmingham City Hospital
Dudley Road
Birmingham
B18 7QH
United Kingdom

Trial participating centre

Cannock Chase Hospital
Brunswick Road
Cannock
WS11 5XY
United Kingdom

Trial participating centre

Chapel Allerton
Chapeltown Road
Leeds
LS7 4SA
United Kingdom

Trial participating centre

University Hospital of North Durham
Durham North Road
Durham
DH1 5TW
United Kingdom

Trial participating centre

Darlington Memorial Hospital
Hollyhurst Rd
Darlington
DL3 6HX
United Kingdom

Trial participating centre

Croydon University Hospital
530 London Road
Croydon
CR7 7YE
United Kingdom

Trial participating centre

Doncaster Royal Infirmary
Armthorpe Rd
Doncaster
DN2 5LT
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Road
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

The Great Western Hospital
Marlborough Road
Swindon
SN3 6BB
United Kingdom

Trial participating centre

Gartnaval General Hospital
1053 Great Western Road
G12 0YN
United Kingdom

Trial participating centre

Glasgow Royal Infirmary
84 Castle Street
Glasgow
G4 0SF
United Kingdom

Trial participating centre

Guy’s Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom

Trial participating centre

Homerton University Hospital
Homerton Row
London
E9 6SR
United Kingdom

Trial participating centre

The James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Trial participating centre

University Hospital Lewisham
High Street Lewisham
London
SE13 6LH
United Kingdom

Trial participating centre

Manchester Royal Infirmary
Oxford Rd
Manchester
M13 9WL
United Kingdom

Trial participating centre

Mile-End Hospital
Bancroft Road
London
E1 4DG
United Kingdom

Trial participating centre

Nuffield Orthopedic Hospital
Windmill Rd
Oxford
OX3 7LD
United Kingdom

Trial participating centre

Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom

Trial participating centre

Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom

Trial participating centre

University Elizabeth Hospital
Queen Elizabeth Medical Centre
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Queen Elizabeth Hospital Gateshead
Queen Elizabeth Avenue
Gateshead
NE9 6SX
United Kingdom

Trial participating centre

Queen’s Hospital Burton
Belvedere Rd
Burton-on-Trent
DE13 0RB
United Kingdom

Trial participating centre

Queen’s Medical Centre
Derby Rd
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Royal Free Hospital
Pond Street
London
NW3 2QG
United Kingdom

Trial participating centre

Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom

Trial participating centre

Russells Hall Hospital
Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Trial participating centre

Queen Elizabeth Hospital, Woolwich
Stadium Rd
London
SE18 4QH
United Kingdom

Trial participating centre

University College London Hospital
235 Euston Rd Fitzrovia
London
NW1 2BU
United Kingdom

Trial participating centre

Wishaw General Hospital
50 Netherton St
Wishaw
ML2 0DP
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

c/o Mr Keith Brennan
Hodgkin Building
Guy's Campus
London
SE1 4UL
United Kingdom

Sponsor type

University/education

Website

http://www.kcl.ac.uk/

Organisation

Guy's & St Thomas' Foundation NHS Trust

Sponsor details

c/o Karen Ignatian
R&D Department
16th Floor
Tower Wing
Great Maze Pond
London
SE1 9RT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research council

Funder name

Medical Research Council [MRC] (UK) ref: 97747

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 27/01/2016 the overall trial end date was changed from 30/09/2016 to 21/01/2016. On 27/07/2015 the target number of participants was changed from 410 to 274 (final recruitment figure 275).