Rheumatoid ArthritisPhase 4TaSERNCT00920478
Targeting Synovitis in Early Rheumatoid Arthritis
A Phase 4 study testing Musculoskeletal Ultrasound and 28 Joint Disease Activity Score in people with Rheumatoid Arthritis and Polyarthritis, run by NHS Greater Glasgow and Clyde at 3 sites in United Kingdom.
Trial summary
Patients with rheumatoid arthritis are at risk of developing permanent joint damage and disability. This study hopes to identify the most effective way of using existing arthritis medication to minimise the chances of developing permanent disability. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis, Polyarthritis
- What is being tested?
- Musculoskeletal Ultrasound and 28 Joint Disease Activity Score
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Sep 2009to Sep 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients attending Early RA clinics with newly diagnosed RA or anti-CCP +ve Undifferentiated Arthritis (UA)
- Active disease (DAS28 > 3.2)
- DMARD naïve or DMARD monotherapy for less than 6 weeks
- Aged 18 or more
Who cannot join
- Significant liver disease and/or abnormality of liver function tests
- AST / ALT > x2 normal, Alkaline Phosphatase > x2.5 normal
- Renal impairment - serum creatinine > 200 μmol/l, eGFR < 30
- Cytopenias - white cell count < 4.0, haemoglobin < 10, platelet < 150
- Pregnancy or planned pregnancy
- Contraindication to MRI
- Other co-morbid condition that in the opinion of the investigator would preclude the use of sequential or combination DMARD therapy
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
Department of Rheumatology, Gartnavel General Hospital
Glasgow, G12 0YN
Duncan Porter, MBChB, +44 141 211 3000, duncan.porter@ggc.scot.nhs.uk
Duncan Porter, MBChB, MRCP
- Recruiting
Department of Rheumatology, Stobhill Hospital
Glasgow, G21 3UW
Hilary Wilson, MD, MRCP, +44 141 211 3307, hilary.wilson@ggc.scot.nhs.uk
Hilary Wilson, MD, MRCP
- Recruiting
Centre for Rheumatic Diseases, Glasgow Royal Infirmary
Glasgow, G4 0SF
David McCarey, MBChB, FRCP, +44 141 2114965, david.mccarey@ggc.scot.nhs.uk
David McCarey, MD, FRCP
About this study
Official title: Targeting Synovitis in Early Rheumatoid Arthritis (TaSER). Intensive Management of Early Rheumatoid Arthritis Using Either Clinical or Musculoskeletal Ultrasound Assessment of Synovitis - a Randomised Study With Blinded Outcome Assessments
Patients with rheumatoid arthritis are at risk of developing permanent joint damage and disability. This study hopes to identify the most effective way of using existing arthritis medication to minimise the chances of developing permanent disability. Patients will have their arthritis activity assessed using an ultrasound machine. If there is still evidence of active arthritis the participant's arthritis medication will be increased until the arthritis is in remission. The effectiveness of this approach will be compared to the traditional method of assessing arthritis using clinical examination.
Furthermore, it is extremely important to identify those patients most at risk of aggressive disease. The investigators hope to produce a more accurate measurement of disease prognosis by examining the relationship between a series of blood tests and how well controlled rheumatoid arthritis appears after 18 months of therapy. Some patients will also be asked to donate samples of joint fluid and joint lining for additional analysis.
Read the detailed description
PURPOSE 1 - to determine whether it is possible to achieve better control of inflammatory joint disease activity in early rheumatoid arthritis by using musculoskeletal ultrasound, instead of clinical examination, to identify the presence, or absence, of synovitis
NULL HYPOTHESIS 1 - using musculoskeletal ultrasound to confirm / refute the presence of ongoing synovitis will NOT allow better control of early rheumatoid arthritis nor prevent progression of destructive joint disease despite patients receiving more intensive disease modifying therapy regimens
PURPOSE 2 - to determine whether baseline measures of certain biochemical and pathological factors, associated with the development of inflammatory synovitis, are predictive of response to therapy in early rheumatoid arthritis and short term outcome measures of inflammatory joint disease activity, functional ability and quality of life
NULL HYPOTHESIS 2 - serial measures of biochemical and pathological factors, associated with the development of inflammatory synovitis, will NOT correlate with short term outcome measures of disease activity and therefore cannot be used to predict a patient's prognosis nor identify those at risk of progressive, destructive joint disease
TRIAL DESIGN - randomised, prospective single blinded trial of treatment strategy with a nested study correlating baseline measures and 18 month outcomes
Investigators will not be blinded to treatment group. Treatment decisions and escalation of therapy will be dictated by a standardised protocol. The sequence of therapy escalation will be identical for both groups. The groups will differ on the threshold needed to progress to the next treatment step
Assessors of disease activity, radiological and pathological outcomes will be blinded to treatment group and their findings will form the basis of each groups final outcome measures
TREATMENT PROTOCOL - the sequence of therapy escalation will be the same for each group. The groups differ by the 'trigger' required to progress to the next treatment step. Therapy will escalated in each group if the measured disease activity exceeds that groups threshold trigger. Changes in DMARD therapy doses and/or combinations take three months to reach maximum effect; therefore, at least a three month gap will be left between each treatment escalation
PRIMARY OUTCOME MEASURE
- Magnetic Resonance Imaging of Dominant Wrist - baseline and 18 months. Images will be scored using the OMERACT RAMRIS(Rheumatoid Arthritis Magnetic Resonance Imaging Score) atlas. The change in each patient's synovitis and erosion scores will be pooled and compared for each intervention group
- 44 joint Disease Activity Score - Mean change of DAS44 with time will represent the rate of response to treatment. Mean area under curve DAS44 will represent overall level of disease activity throughout the study period
SECONDARY OUTCOME MEASURES
- European League Against Rheumatism Response Rates - A EULAR Good response is defined as a greater than 1.2 change in DAS44 and a final DAS44 less than 2.4. Disease remission is defined as DAS44 less than 1.6
- Functional Measures - Health Assessment Questionnaire and EuroQoL-5D questionnaires at enrollment and then every 3 months.
- Plain Xrays - plain xrays of hands, wrists and feet at baseline and 18 months. Change in Sharp score between baseline and 18 month films will be reported
- Biomarker analysis - analyses will include specific genetic factors(genomic DNA), gene expression (RNA analysis), novel autoantibody assays, cytokine / emerging inflammatory protein profiling, lipid / lipoprotein based markers, metabolic assays and assessment of bone and cartilage turnover markers.
Samples will be collected at baseline, 3 months and 12 months (if not commenced on etanercept), immediately before commencing etanercept, 3 months and 6 months after commencing etanercept and 3 months after cessation. Final disease outcome measures for each patient will be correlated with baseline biomarker values to determine if any predictive relationships exist.
All values will be entered into a logistical regression analysis to try and create a statistical predictive model. Serial biomarker analyses will demonstrate how the different components of the pathogenetic process respond to the different stages of DMARD therapy.
- Conditions
- Rheumatoid Arthritis, Polyarthritis
- Being tested
- Musculoskeletal Ultrasound, 28 Joint Disease Activity Score
- Keywords
- Rheumatoid arthritis, Musculoskeletal Ultrasound, Synovitis, DMARD, Etanercept, Biomarkers, Undifferentiated Inflammatory Polyarthritis
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis, Synovitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Musculoskeletal UltrasoundOther
Gray scale and power doppler - to identify the presence of synovitis
28 Joint Disease Activity ScoreOther
Clinical assessment of synovitis - composite score incorporating 28 tender joint count, 28 swollen joint count, erythrocyte sedimentation rate and patient global VAS
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Active comparator | Inflammatory disease activity assessed using DAS28 Receives: Other: 28 Joint Disease Activity Score |
| Ultrasound Group | Experimental | Inflammatory disease activity assessed using musculoskeletal ultrasound (gray scale and power doppler) Receives: Other: Musculoskeletal Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
MRI RAMRIS Erosion Score
Measured: Baseline and 18 months
44 Joint Disease Activity Score
Measured: Baseline, 3, 6, 9, 12, 15 and 18 months
Secondary outcomes (6)
Plain Xray - Hands and Feet - modified Sharp score
Measured: Baseline and 18 months
Health Assessment Questionnaire
Measured: Baseline, 3, 6, 9, 12, 15 and 18 months
Euro-Qol 5D
Measured: Baseline, 3, 6, 9, 12, 15 and 18 months
EULAR response and remission rates
Measured: Baseline and 18 months
Biomarker analysis - correlation between baseline values and 18 month radiological outcomes
Measured: Baseline
Adverse event rates
Measured: Throughout period of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2009 (estimated)
- Study startSep 2009
- Primary completionSep 2012 (estimated)
- Study completionSep 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NHS Greater Glasgow and Clyde
- Sponsor type
- University, hospital or other
- Collaborators
- University of Glasgow, Chief Scientist Office of the Scottish Government, Wyeth is now a wholly owned subsidiary of Pfizer, Translational Medicine Research Collaboration
- Investigators
- Duncan R Porter, MBChB, MRCP, Study chair, Gartnavel General Hospital, GlasgowJames E Dale, MBChB, MRCP, Principal investigator, University of GlasgowIain B McInnes, PhD, FRCP, Study chair, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00920478
- Sponsor's protocol ID
- GN09RH196
- Other IDs
- CSO - CAF / 08 / 03
- Acronym
- TaSER
- Status last verified
- Sep 2009
- First submitted
- 11 Jun 2009
- Last updated
- 10 Sep 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Dale J, Stirling A, Zhang R, Purves D, Foley J, Sambrook M, Conaghan PG, van der Heijde D, McConnachie A, McInnes IB, Porter D. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Ann Rheum Dis. 2016 Jun;75(6):1043-50. doi: 10.1136/annrheumdis-2015-208941. Epub 2016 Mar 29.
PubMed 27026689Dale J, Purves D, McConnachie A, McInnes I, Porter D. Tightening up? Impact of musculoskeletal ultrasound disease activity assessment on early rheumatoid arthritis patients treated using a treat to target strategy. Arthritis Care Res (Hoboken). 2014 Jan;66(1):19-26. doi: 10.1002/acr.22218.
PubMed 24376248
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Synovitis in Early Rheumatoid Arthritis (TaSER). Intensive Management of Early Rheumatoid Arthritis Using Either Clinical or Musculoskeletal Ultrasound Assessment of Synovitis - a Randomised Study With Blinded Outcome Assessments
- ClinicalTrials.gov ID
- NCT00920478
- Acronym / sponsor ID
- TaSER / GN09RH196
- Conditions
- Rheumatoid Arthritis, Polyarthritis
- Keywords
- Rheumatoid arthritis, Musculoskeletal Ultrasound, Synovitis, DMARD, Etanercept, Biomarkers, Undifferentiated Inflammatory Polyarthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- NHS Greater Glasgow and ClydeUniversity, hospital or other
- Collaborators
- University of Glasgow, Chief Scientist Office of the Scottish Government, Wyeth is now a wholly owned subsidiary of Pfizer, Translational Medicine Research Collaboration
- Study start
- Sep 2009
- Primary completion
- Sep 2012 (estimated)
- Study completion
- Sep 2012 (estimated)
- First posted
- 15 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with rheumatoid arthritis are at risk of developing permanent joint damage and disability. This study hopes to identify the most effective way of using existing arthritis medication to minimise the chances of developing permanent disability. Patients will have their arthritis activity assessed using an ultrasound machine. If there is still evidence of active arthritis the participant's arthritis medication will be increased until the arthritis is in remission. The effectiveness of this approach will be compared to the traditional method of assessing arthritis using clinical examination.
Furthermore, it is extremely important to identify those patients most at risk of aggressive disease. The investigators hope to produce a more accurate measurement of disease prognosis by examining the relationship between a series of blood tests and how well controlled rheumatoid arthritis appears after 18 months of therapy. Some patients will also be asked to donate samples of joint fluid and joint lining for additional analysis.
Detailed description
PURPOSE 1 - to determine whether it is possible to achieve better control of inflammatory joint disease activity in early rheumatoid arthritis by using musculoskeletal ultrasound, instead of clinical examination, to identify the presence, or absence, of synovitis
NULL HYPOTHESIS 1 - using musculoskeletal ultrasound to confirm / refute the presence of ongoing synovitis will NOT allow better control of early rheumatoid arthritis nor prevent progression of destructive joint disease despite patients receiving more intensive disease modifying therapy regimens
PURPOSE 2 - to determine whether baseline measures of certain biochemical and pathological factors, associated with the development of inflammatory synovitis, are predictive of response to therapy in early rheumatoid arthritis and short term outcome measures of inflammatory joint disease activity, functional ability and quality of life
NULL HYPOTHESIS 2 - serial measures of biochemical and pathological factors, associated with the development of inflammatory synovitis, will NOT correlate with short term outcome measures of disease activity and therefore cannot be used to predict a patient's prognosis nor identify those at risk of progressive, destructive joint disease
TRIAL DESIGN - randomised, prospective single blinded trial of treatment strategy with a nested study correlating baseline measures and 18 month outcomes
Investigators will not be blinded to treatment group. Treatment decisions and escalation of therapy will be dictated by a standardised protocol. The sequence of therapy escalation will be identical for both groups. The groups will differ on the threshold needed to progress to the next treatment step
Assessors of disease activity, radiological and pathological outcomes will be blinded to treatment group and their findings will form the basis of each groups final outcome measures
TREATMENT PROTOCOL - the sequence of therapy escalation will be the same for each group. The groups differ by the 'trigger' required to progress to the next treatment step. Therapy will escalated in each group if the measured disease activity exceeds that groups threshold trigger. Changes in DMARD therapy doses and/or combinations take three months to reach maximum effect; therefore, at least a three month gap will be left between each treatment escalation
PRIMARY OUTCOME MEASURE
- Magnetic Resonance Imaging of Dominant Wrist - baseline and 18 months. Images will be scored using the OMERACT RAMRIS(Rheumatoid Arthritis Magnetic Resonance Imaging Score) atlas. The change in each patient's synovitis and erosion scores will be pooled and compared for each intervention group
- 44 joint Disease Activity Score - Mean change of DAS44 with time will represent the rate of response to treatment. Mean area under curve DAS44 will represent overall level of disease activity throughout the study period
SECONDARY OUTCOME MEASURES
- European League Against Rheumatism Response Rates - A EULAR Good response is defined as a greater than 1.2 change in DAS44 and a final DAS44 less than 2.4. Disease remission is defined as DAS44 less than 1.6
- Functional Measures - Health Assessment Questionnaire and EuroQoL-5D questionnaires at enrollment and then every 3 months.
- Plain Xrays - plain xrays of hands, wrists and feet at baseline and 18 months. Change in Sharp score between baseline and 18 month films will be reported
- Biomarker analysis - analyses will include specific genetic factors(genomic DNA), gene expression (RNA analysis), novel autoantibody assays, cytokine / emerging inflammatory protein profiling, lipid / lipoprotein based markers, metabolic assays and assessment of bone and cartilage turnover markers.
Samples will be collected at baseline, 3 months and 12 months (if not commenced on etanercept), immediately before commencing etanercept, 3 months and 6 months after commencing etanercept and 3 months after cessation. Final disease outcome measures for each patient will be correlated with baseline biomarker values to determine if any predictive relationships exist.
All values will be entered into a logistical regression analysis to try and create a statistical predictive model. Serial biomarker analyses will demonstrate how the different components of the pathogenetic process respond to the different stages of DMARD therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Active comparator | Other: 28 Joint Disease Activity ScoreInflammatory disease activity assessed using DAS28 |
| Ultrasound Group | Experimental | Other: Musculoskeletal UltrasoundInflammatory disease activity assessed using musculoskeletal ultrasound (gray scale and power doppler) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients attending Early RA clinics with newly diagnosed RA or anti-CCP +ve Undifferentiated Arthritis (UA)
- Active disease (DAS28 > 3.2)
- DMARD naïve or DMARD monotherapy for less than 6 weeks
- Aged 18 or more
Key exclusion criteria (7 listed)
- Significant liver disease and/or abnormality of liver function tests
- AST / ALT > x2 normal, Alkaline Phosphatase > x2.5 normal
- Renal impairment - serum creatinine > 200 μmol/l, eGFR < 30
- Cytopenias - white cell count < 4.0, haemoglobin < 10, platelet < 150
- Pregnancy or planned pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Musculoskeletal UltrasoundGray scale and power doppler - to identify the presence of synovitis | Other | Ultrasound Group |
| 28 Joint Disease Activity ScoreClinical assessment of synovitis - composite score incorporating 28 tender joint count, 28 swollen joint count, erythrocyte sedimentation rate and patient global VAS | Other | Control Group |
Primary outcome
MRI RAMRIS Erosion Score
Time frame: Baseline and 18 months
44 Joint Disease Activity Score
Time frame: Baseline, 3, 6, 9, 12, 15 and 18 months
6 secondary outcomes
Plain Xray - Hands and Feet - modified Sharp score
Time frame: Baseline and 18 months
Health Assessment Questionnaire
Time frame: Baseline, 3, 6, 9, 12, 15 and 18 months
Euro-Qol 5D
Time frame: Baseline, 3, 6, 9, 12, 15 and 18 months
EULAR response and remission rates
Time frame: Baseline and 18 months
Biomarker analysis - correlation between baseline values and 18 month radiological outcomes
Time frame: Baseline
Adverse event rates
Time frame: Throughout period of study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2009.
- Derived from this study: PubMed 27026689Dale J, Stirling A, Zhang R, Purves D, Foley J, Sambrook M, Conaghan PG, van der Heijde D, McConnachie A, McInnes IB, Porter D. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Ann Rheum Dis. 2016 Jun;75(6):1043-50. doi: 10.1136/annrheumdis-2015-208941. Epub 2016 Mar 29.
- Derived from this study: PubMed 24376248Dale J, Purves D, McConnachie A, McInnes I, Porter D. Tightening up? Impact of musculoskeletal ultrasound disease activity assessment on early rheumatoid arthritis patients treated using a treat to target strategy. Arthritis Care Res (Hoboken). 2014 Jan;66(1):19-26. doi: 10.1002/acr.22218.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Duncan R Porter, MBChB, MRCP study chair
Gartnavel General Hospital, Glasgow
James E Dale, MBChB, MRCP principal investigator
University of Glasgow
Iain B McInnes, PhD, FRCP study chair
University of Glasgow
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Musculoskeletal Ultrasound and 28 Joint Disease Activity Score in people with Rheumatoid Arthritis and Polyarthritis, run by NHS Greater Glasgow and Clyde at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James Dale, MBChB, MRCP (+44 141 211 3000 ext. 3008, james.dale@ggc.scot.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MRI RAMRIS Erosion Score (time frame: Baseline and 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00920478, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2009.