Giant Cell ArteritisTABULNCT00974883
Temporal Artery Biopsy vs ULtrasound in Diagnosis of GCA (TABUL)
An observational study of Giant Cell Arteritis, run by University of Oxford at 27 sites in 5 countries.
Trial summary
Giant Cell Arteritis (GCA) causes inflammation and narrowing of blood vessels and can cause blindness in one third of patients. It is important that a prompt, accurate diagnosis of GCA is made and treatment given as steroids for two or more years. Currently there is no 100% accurate test for GCA. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Giant Cell Arteritis
- What is being tested?
- Ultrasound of temporal and axillary arteries and Temporal artery biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 880 participants
- Where
- 27 sitesin 5 countries
- Study dates
- Jun 2010to Dec 2014
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study cohort: Patients with suspected new giant cell arteritis Training cohort; patients or healthy volunteers willing to have temporal artery and axillary artery ultrasound examination
Who may be able to join
- A clinical suspicion of new diagnosis of GCA e.g. patients with a new onset of headache, scalp tenderness, with or without elevated CRP or ESR, jaw or tongue claudication with or without visual loss.
- The clinician decides that the patient requires an urgent temporal artery biopsy to determine whether or not the diagnosis is GCA.
- The patient agrees and provides NHS consent to undergo a temporal artery biopsy as part of standard care.
- Patients have been started on high dose glucocorticoids or will be started on high dose glucocorticoids.
- Patients must be willing to attend for an ultrasound scan of their temporal and axillary arteries.
- Participants must be willing to give informed written consent or willing to give permission for a nominated friend or relative to provide written informed assent if they are unable to do so because of physical disabilities e.g. sudden onset of blindness/vision loss which can be caused by GCA (this will be made clear in the ethics approval application).
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- Must be 18 years of age or over.
- For the training cases
- Patients attending hospital outpatient or in patient departments for assessment for any condition (apart from giant cell arteritis or polymyalgia rheumatica) or healthy staff volunteers.
- Above the age of 50 years.
- Willing to attend for an ultrasound scan of their temporal and axillary arteries.
- Willing and able to give written informed consent.
Who cannot join
- Previous diagnosis of GCA.
- Use of high dose glucocorticoid (>20mg prednisolone/day) for management of current suspected GCA for more than 7 days prior to the dates of the ultrasound and biopsy.
- Long term (>1 month) high dose (>20mg per day at any time) steroids for conditions other than PMR, within three months prior to study entry.
- Inability to give informed consent (either written consent or verbal assent from a relative or carer)
- Inability to undergo an ultrasound scans of the temporal and axillary arteries.
- Patients with a known cause of headache (not due to GCA), or any condition which would preclude the need for a temporal artery biopsy.
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- Patients who are unable to undergo an ultrasound scan and a temporal artery biopsy within 7 days of starting glucocorticoids.
- For the training cases
- Diagnosis of suspected GCA or a previous history of diagnosed or suspected GCA.
- Inability to give written informed consent.
- Inability to undergo an ultrasound scans of the temporal and axillary arteries
Trial locations and contacts
27 sites in 5 countries.
27 sites in 5 countries
United Kingdom23 sites
Stoke Mandeville Hospital
Aylesbury, HP21 8AL
Musgrave Park Hospital
Belfast, BT0 7JB
City Hospital Birmingham
Birmingham, B18 7QH
West Suffolk NHS Foundation Trust
Bury St Edmunds, IP33 2QZ
Derbyshire Royal Infirmary
Derby, DE1 2QY
Dudley Group of Hospitals
Dudley, DY1 2HY
Gateshead Health NHS Foundation Trust
Gateshead, NE9 6SX
James Paget University Hospitals NHS Foundation Trust
Great Yarmouth, NR31 6LA
Princess Alexandra Hospital
Harlow, Essex, CM20 1QX
Leeds University NHS Trust
Leeds, LS7 4SA
James Cook University Hospital,
Middlesbrough
Northampton Hospital
Northampton
Norfolk and Norwich Hospiital
Norwich, NR4 7UY
Queens Medical Centre
Nottingham, NG7 2UH
Nuffield Orthopaedic Centre NHS Trust
Oxford, Oxfordshire, OX3 7LD
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
University of Oxford
Oxford, OX1 3RE
The Pennine Acute Hospitals NHS Trust
Pennine Rheumatology Centre, Rochdale Infirmary, OL12 0NB
Queen Alexandra Hospital
Portsmouth, PO6 3LY
Royal Berkshire
Reading, RG1 5AN
Queens Hospiital
Romford, RM7 0BE
Southend University Hospital
Southend, SSO 0EF
Sunderland Royal Hospital
Sunderland
About this study
Official title: The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (GCA).
Giant Cell Arteritis (GCA) causes inflammation and narrowing of blood vessels and can cause blindness in one third of patients. It is important that a prompt, accurate diagnosis of GCA is made and treatment given as steroids for two or more years. Currently there is no 100% accurate test for GCA. Patients usually have new headache and scalp tenderness, typically with an abnormal blood test. However, it can be difficult to distinguish non-serious forms of headache from GCA; infection produces similar abnormal blood results. If there is a suspicion of GCA, treatment with steroids is started straight away. To confirm a diagnosis, the patient will need a biopsy of a temporal artery (a minor procedure performed under local anaesthetic to remove a sample of one of the scalp arteries). However, up to 44% of patients will have a normal biopsy. Therefore it is difficult to know if a patient with a normal biopsy does or does not have GCA. Withdrawing steroid treatment may increase the risk of blindness. Continuing treatment in a patient without GCA increases the risk of side effects (e.g., weight gain, infection risk, osteoporosis and fracture risk, high blood pressure, diabetes, cataracts). It is important to improve diagnostic tests for GCA. Another test to help in diagnosing GCA is an ultrasound scan of the arteries in the side of the head and under the arms. Ultrasound does not involve surgery; it is a simple test which can be performed as an out patient. Gel is applied to both sides of the head and under each arm. A sound probe is placed over the artery at each site to produce the scan.
The investigators' study will examine the role of ultrasound in diagnosis of 402 patients with suspected GCA. All patients will have an ultrasound examination in addition to biopsy within a week of starting steroids. Patients will be treated according to usual practice. After six months, the investigators will reassess the diagnosis. The investigators will look at the accuracy of ultrasound compared with or combined with biopsy. The investigators will look at how a doctor's knowledge of ultrasound results or biopsy results alone would affect the diagnosis and recommendation to continue or stop steroid treatment. The investigators will assess whether knowledge of both results together would alter the diagnosis and treatment. The investigators will collect information to estimate the costs of different ways of diagnosing GCA in relation to the impact on quality of life.
Read the detailed description
OVERALL DESIGN: The overall design consists of a cohort study of 402 participants with suspected GCA who will be followed up for 6 months; a cost-effectiveness study comparing ultrasound with temporal artery biopsy; a study of observer agreement in evaluating ultrasound and temporal artery biopsies; and an expert panel assessing the appropriateness of alternative strategies for diagnosing and treating patients with suspected GCA.
PRIMARY OBJECTIVES:
- To evaluate the diagnostic accuracy (sensitivity and specificity) of ultrasound as an alternative to temporal artery biopsy for the diagnosis of GCA in patients referred for biopsy with suspected GCA.
- To evaluate the cost-effectiveness (incremental cost per QALY) of ultrasound instead of biopsy in the diagnosis of GCA. SECONDARY OBJECTIVES:
- To evaluate inter-observer agreement in the assessment of ultrasound and temporal artery biopsy.
- To elicit expert views on the appropriateness of performing a biopsy following ultrasound using clinical vignettes.
- To evaluate the diagnostic accuracy (sensitivity and specificity) of the sequential diagnostic strategy from 4 as an alternative to temporal artery biopsy alone in the diagnosis of GCA.
- To evaluate the cost-effectiveness (incremental cost per QALY) of the diagnostic strategy from 4 instead of biopsy alone in the diagnosis of GCA.
DESIGN:
A prospective cohort study to evaluate the impact of ultrasound or biopsy of temporal arteries on diagnosis of GCA and treatment decisions . The cohort study will use a paired design, i.e. all participants will have both US and biopsy, with diagnostic performance assessed against a composite reference standard diagnosis following final (6 months) assessment. To evaluate the impact of US/biopsy results on clinical practice and longer term outcomes, we will derive clinical vignettes based on cases recruited to the study, and present them to the treating clinician, along with either the ultrasound, or biopsy or both results, so that they can indicate diagnosis and proposed treatment. The main cost-effectiveness analyses will evaluate incremental cost per quality adjusted life year (QALY) on a long term (lifetime) horizon between diagnostic strategies.
SETTING:
Outpatient and inpatient rheumatology and ophthalmology departments in 25 National Health Service (NHS) trusts in the United Kingdom (UK) (also sites in Europe of required) with access to high resolution US.
TARGET POPULATION: Patients with suspected GCA who would normally require an urgent temporal artery biopsy, i.e. referrals from primary care and suspected GCA identified in secondary care. Recruitment of participants will be restricted to patients for whom US and biopsy can be performed within 7 days of starting high-dose steroids.
HEALTH TECHNOLOGIES BEING ASSESSED:
Halo, stenosis, or occlusion assessed by high resolution US; presence of giant cells or granulomatous inflammation on temporal artery biopsy.
MEASUREMENT OF COST AND OUTCOMES:
Data collection at baseline, 2 weeks and 6 months will include clinical and laboratory markers of disease activity, resource use, health-related quality of life (HRQoL) using the EuroQol-5D (EQ-5D), and adverse events. Baseline assessment will include retrospective assessment of symptoms and erythrocyte sedimentation rate/C-reactive protein (ESR/CRP) results before starting steroids. The reference standard diagnosis will be made using a composite of American College of Rheumatology classification criteria, GCA-related events, and alternative diagnoses using data collected at all assessments. Proposed treatment data will be collected from participating clinicians after each test result is released, and classified as treatment for GCA (e.g. initiate/continue steroids) or not GCA (e.g. withdraw/rapid taper of steroids) to compare changes in proposed treatment and evaluate agreement with the reference diagnosis. Unit costs of resources used will be obtained from nationally published sources where available. Modelling will estimate the impact of diagnostic strategies on clinical outcomes (e.g. GCA complications and steroid related adverse events), their costs and impact on HRQoL beyond study follow-up and within study follow-up. Probabilities of events, their cost and impact will be obtained from study data, a systematic literature review, or in the absence of relevant data, by formal elicitation of expert opinion. Costs and benefits will be discounted at 3.5% (National Institute for Health and Care Excellence [NICE] guidance) and uncertainty (including modelling assumptions) subjected to probabilistic sensitivity analysis and scenario analysis.
SAMPLE SIZE:
A sample size of 402 patients provides 90% power at a 5% type I error rate to test the joint hypothesis that (i) US has greater sensitivity than biopsy (to detect an increase in sensitivity from 76% for biopsy (assuming a 0.24 false negative fraction based on 9-44% biopsy-negative GCA) to 87% sensitivity for US; and (ii) to detect specificity of US of no less than 0.83 based on an expected specificity of 0.96. This sample size will allow estimation of a one-sided rectangular confidence region for US false and true positive fractions, assuming 80% prevalence of GCA in patients having a biopsy for suspected GCA, with the sample size inflated (gamma=0.1) due to uncertainty in the proportion of cases/controls in a cohort design. We will actually recruit 430 cases to allow for possible drop-outs from the study. In addition we will recruit 270 individuals for training purposes, to allow each centre to learn the technique of temporal artery and axillary artery scanning. Each centre will collect 10 such individuals (training cases), who will be of similar age and gender as the study cohort, but who will not have temporal arteritis. This is very important in order to ensure that observers are trained to recognise the appearances seen in normal (non GCA arteries) especially patients with atherosclerosis. Further ultrasound training including a video exam (to identify images of both normal and abnormal features of GCA) and a 'hot' case assessment (scanning a patient with GCA) will be designed into the ultrasound training programme. In addition, we will provide adequate training days (e.g. 2 separate training days) when all observers will be trained formally by Dr Schmidt and other ultrasound experts to ensure adequate observer agreement. The first training day will be held prior to starting the recruitment of patients, and will be repeated after the first year.
PROJECT TIMETABLE:
Total: 48 months (UPDATED TO 60 MONTHS SEE BELOW) Month 1-6 Study materials/protocols prepared; Ethics and research governance approval complete; Centres trained, approved and ready to recruit.
Month 7-12 Recruitment monitoring report; Quality control report. Month 13-18 Recruitment monitoring report; Quality control report; Additional centres (if required) trained, approved and ready to recruit; Month 19-24 Recruitment monitoring report; Quality control report. Month 25-30 Recruitment monitoring report; Quality control report; Web-based US and biopsy assessment developed.
Month 31-36 Recruitment completed; Clinical vignettes (web-based) developed. Month 37-42 Follow-up completed; Inter-rater assessment of US and biopsy images analysis competed; Expert panel review of vignettes completed.
Month 43-48 Database cleaned and locked; Analysis completed; statistical analysis and economic modelling, report drafting and preparation of papers. Final report completed.
PLEASE NOTE: 12 MONTH EXTENSION WAS GRANTED BY THE FUNDER (NIHR HTA) IN SEPTEMBER 2012 TO EXTEND THE RECRUITMENT PERIOD FROM THE END OF DECEMBER 2012 TO END OF DECEMBER 2013 (A FURTHER 12 MONTHS).
TH END OF STUDY WILL NOW BE DECEMBER 2014
The study will be overseen by a Trial Steering Committee (TSC) and an independent Data Monitoring Committee (DMC)at least 1 meeting per year.
BIOBANK:
We will develop a biobank of tissue, serum, DNA and ultrasound video imaging of blood vessels in GCA. An important benefit of the primary protocol is that we can use the accumulated material for a number of related projects.
- Conditions
- Giant Cell Arteritis
- Being tested
- Ultrasound of temporal and axillary arteries, Temporal artery biopsy
- Keywords
- ultrasound, GCA, temporal arteritis, biopsy
- Medical subject headings
- Giant Cell Arteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ultrasound of temporal and axillary arteriesProcedure or surgery
Also called Ultrasound scan
Standardised assessment of temporal arteries and axillary arteries using high resolution ultrasound to detect halo, stenosis or occlusion
Temporal artery biopsyProcedure or surgery
Also called Biopsy of temporal artery
Biopsy of temporal artery from symptomatic side
| Study group | Role | What they receive |
|---|---|---|
| Suspected GCA | Patients who present with new onset of headache and suspected diagnosis of GCA. They will all require a temporal artery biopsy to assist in the diagnosis Receives: Procedure: Ultrasound of temporal and axillary arteries; Procedure: Temporal artery biopsy | |
| Training cohort | Patients with any condition or healthy volunteers who are willing to consent ot have their temporal and axillary arteries examined using ultrasound, for training purposes Receives: Procedure: Ultrasound of temporal and axillary arteries |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the diagnostic accuracy of ultrasound vs temporal artery biopsy for diagnosis of suspected GCA and to evaluate the cost-effectiveness (incremental cost per QALY) of ultrasound instead of biopsy in the diagnosis of GCA.
Measured: Six months
Secondary outcomes (13)
To evaluate inter-observer agreement in the assessment of ultrasound and temporal artery biopsy
Measured: Six months
To elicit expert views on the appropriateness of performing a biopsy following ultrasound using clinical vignettes
Measured: 3 years
To evaluate the diagnostic accuracy (sensitivity and specificity) of the sequential diagnostic strategy as an alternative to temporal artery biopsy alone in the diagnosis of GCA
Measured: 3 years
To evaluate the cost-effectiveness (incremental cost per QALY) of the diagnostic strategy of combined ultrasound and biopsy instead of biopsy alone in the diagnosis of GCA.
Measured: 3 years
Specific adverse events measured at each assessment; daily and cumulative steroid dose; steroid side effects; and pain or dysaesthesia at the biopsy site.
Measured: Six months
Evolution of an alternative diagnosis
Measured: Six months
Negative predictive value of ultrasound in preventing the need for temporal artery biopsies.
Measured: Six months
Cost analysis of performing a screening ultrasound examination plus biopsy as part of the diagnostic workup of all patients with suspected GCA; or of performing a screening ultrasound examination instead of biopsy; or of performing a screening ultrasound
Measured: Six months
Cost analysis of performing a screening ultrasound examination instead of biopsy in cases with a very low probability of GCA as part of the diagnostic workup of all patients with suspected GCA.
Measured: 3 years
Prediction of potential harm done to patients by over diagnosis or under diagnosis of GCA as a result of ultrasound use, either alone or in combination with biopsy
Measured: 3 years
Value of axillary artery ultrasound scanning in contributing to the diagnosis of GCA.
Measured: Six months
Analysis of proportion of patients with a biopsy positive halo, stenosis, or occlusion assessed by high resolution ultrasound
Measured: 3 years
Presence of characteristic features of GCA on temporal artery biopsy in relation to clinical and ultrasound findings
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2009 (estimated)
- Study startJun 2010
- Primary completionDec 2013
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Giant Cell ArteritisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 880 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University of Sheffield, Mid and South Essex NHS Foundation Trust, Nuffield Orthopaedic Centre NHS Trust, Oxford University Hospitals NHS Trust, The Leeds Teaching Hospitals NHS Trust, University of Bristol, London School of Hygiene and Tropical Medicine, Medical Center for Rheumatology Berlin-Buch
- Responsible party
- Sponsor
- Investigators
- Raashid A Luqmani, DM FRCP, Study chair, University of OxfordAndrew Hutchings, Principal investigator, London School of Hygiene and Tropical MedicineMike Bradburn, Principal investigator, University of SheffieldBhaskar Dasgupta, Principal investigator, University Hospital SouthendAllan Wailoo, Principal investigator, University of SheffieldJohn Salmon, Principal investigator, John Radcliffe Hospital, OxfordEugene McNally, Principal investigator, Nuffield Orthopaedic Centre OxfordWilliam Hamilton, Principal investigator, University of Bristol
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00974883
- Sponsor's protocol ID
- 08/64/01
- Other IDs
- ISRCTN46280267
- Acronym
- TABUL
- Status last verified
- Jul 2015
- First submitted
- 9 Sep 2009
- Last updated
- 17 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990 Aug;33(8):1122-8. doi: 10.1002/art.1780330810.
PubMed 2202311Smeeth L, Cook C, Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Ann Rheum Dis. 2006 Aug;65(8):1093-8. doi: 10.1136/ard.2005.046912. Epub 2006 Jan 13.
PubMed 16414971Borg FA, Salter VL, Dasgupta B. Neuro-ophthalmic complications in giant cell arteritis. Curr Allergy Asthma Rep. 2008 Jul;8(4):323-30. doi: 10.1007/s11882-008-0052-4.
PubMed 18606086Maughan RT, Macdonald-Dunlop E, Haroon-Rashid L, Sorensen L, Chaddock N, Masters S, Porter A, Peverelli M, Pericleous C, Hutchings A, Robinson J, Youngstein T, Luqmani RA, Mason JC, Morgan AW, Peters JE. Proteomic Profiling of the Large-Vessel Vasculitis Spectrum Identifying Shared Signatures of Innate Immune Activation and Stromal Remodeling. Arthritis Rheumatol. 2025 Jul;77(7):884-900. doi: 10.1002/art.43110. Epub 2025 Feb 27.
PubMed 39817309Goodfellow N, Morlet J, Singh S, Sabokbar A, Hutchings A, Sharma V, Vaskova J, Masters S, Zarei A, Luqmani R. Is vascular endothelial growth factor a useful biomarker in giant cell arteritis? RMD Open. 2017 Mar 29;3(1):e000353. doi: 10.1136/rmdopen-2016-000353. eCollection 2017.
PubMed 28405470
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (GCA).
- ClinicalTrials.gov ID
- NCT00974883
- Acronym / sponsor ID
- TABUL / 08/64/01
- Conditions
- Giant Cell Arteritis
- Keywords
- ultrasound, GCA, temporal arteritis, biopsy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 880 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University of Sheffield, Mid and South Essex NHS Foundation Trust, Nuffield Orthopaedic Centre NHS Trust, Oxford University Hospitals NHS Trust, The Leeds Teaching Hospitals NHS Trust, University of Bristol, London School of Hygiene and Tropical Medicine, Medical Center for Rheumatology Berlin-Buch
- Study start
- Jun 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 Sep 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.
Giant Cell Arteritis (GCA) causes inflammation and narrowing of blood vessels and can cause blindness in one third of patients. It is important that a prompt, accurate diagnosis of GCA is made and treatment given as steroids for two or more years. Currently there is no 100% accurate test for GCA. Patients usually have new headache and scalp tenderness, typically with an abnormal blood test. However, it can be difficult to distinguish non-serious forms of headache from GCA; infection produces similar abnormal blood results. If there is a suspicion of GCA, treatment with steroids is started straight away. To confirm a diagnosis, the patient will need a biopsy of a temporal artery (a minor procedure performed under local anaesthetic to remove a sample of one of the scalp arteries). However, up to 44% of patients will have a normal biopsy. Therefore it is difficult to know if a patient with a normal biopsy does or does not have GCA. Withdrawing steroid treatment may increase the risk of blindness. Continuing treatment in a patient without GCA increases the risk of side effects (e.g., weight gain, infection risk, osteoporosis and fracture risk, high blood pressure, diabetes, cataracts). It is important to improve diagnostic tests for GCA. Another test to help in diagnosing GCA is an ultrasound scan of the arteries in the side of the head and under the arms. Ultrasound does not involve surgery; it is a simple test which can be performed as an out patient. Gel is applied to both sides of the head and under each arm. A sound probe is placed over the artery at each site to produce the scan.
The investigators' study will examine the role of ultrasound in diagnosis of 402 patients with suspected GCA. All patients will have an ultrasound examination in addition to biopsy within a week of starting steroids. Patients will be treated according to usual practice. After six months, the investigators will reassess the diagnosis. The investigators will look at the accuracy of ultrasound compared with or combined with biopsy. The investigators will look at how a doctor's knowledge of ultrasound results or biopsy results alone would affect the diagnosis and recommendation to continue or stop steroid treatment. The investigators will assess whether knowledge of both results together would alter the diagnosis and treatment. The investigators will collect information to estimate the costs of different ways of diagnosing GCA in relation to the impact on quality of life.
Detailed description
OVERALL DESIGN: The overall design consists of a cohort study of 402 participants with suspected GCA who will be followed up for 6 months; a cost-effectiveness study comparing ultrasound with temporal artery biopsy; a study of observer agreement in evaluating ultrasound and temporal artery biopsies; and an expert panel assessing the appropriateness of alternative strategies for diagnosing and treating patients with suspected GCA.
PRIMARY OBJECTIVES:
- To evaluate the diagnostic accuracy (sensitivity and specificity) of ultrasound as an alternative to temporal artery biopsy for the diagnosis of GCA in patients referred for biopsy with suspected GCA.
- To evaluate the cost-effectiveness (incremental cost per QALY) of ultrasound instead of biopsy in the diagnosis of GCA. SECONDARY OBJECTIVES:
- To evaluate inter-observer agreement in the assessment of ultrasound and temporal artery biopsy.
- To elicit expert views on the appropriateness of performing a biopsy following ultrasound using clinical vignettes.
- To evaluate the diagnostic accuracy (sensitivity and specificity) of the sequential diagnostic strategy from 4 as an alternative to temporal artery biopsy alone in the diagnosis of GCA.
- To evaluate the cost-effectiveness (incremental cost per QALY) of the diagnostic strategy from 4 instead of biopsy alone in the diagnosis of GCA.
DESIGN:
A prospective cohort study to evaluate the impact of ultrasound or biopsy of temporal arteries on diagnosis of GCA and treatment decisions . The cohort study will use a paired design, i.e. all participants will have both US and biopsy, with diagnostic performance assessed against a composite reference standard diagnosis following final (6 months) assessment. To evaluate the impact of US/biopsy results on clinical practice and longer term outcomes, we will derive clinical vignettes based on cases recruited to the study, and present them to the treating clinician, along with either the ultrasound, or biopsy or both results, so that they can indicate diagnosis and proposed treatment. The main cost-effectiveness analyses will evaluate incremental cost per quality adjusted life year (QALY) on a long term (lifetime) horizon between diagnostic strategies.
SETTING:
Outpatient and inpatient rheumatology and ophthalmology departments in 25 National Health Service (NHS) trusts in the United Kingdom (UK) (also sites in Europe of required) with access to high resolution US.
TARGET POPULATION: Patients with suspected GCA who would normally require an urgent temporal artery biopsy, i.e. referrals from primary care and suspected GCA identified in secondary care. Recruitment of participants will be restricted to patients for whom US and biopsy can be performed within 7 days of starting high-dose steroids.
HEALTH TECHNOLOGIES BEING ASSESSED:
Halo, stenosis, or occlusion assessed by high resolution US; presence of giant cells or granulomatous inflammation on temporal artery biopsy.
MEASUREMENT OF COST AND OUTCOMES:
Data collection at baseline, 2 weeks and 6 months will include clinical and laboratory markers of disease activity, resource use, health-related quality of life (HRQoL) using the EuroQol-5D (EQ-5D), and adverse events. Baseline assessment will include retrospective assessment of symptoms and erythrocyte sedimentation rate/C-reactive protein (ESR/CRP) results before starting steroids. The reference standard diagnosis will be made using a composite of American College of Rheumatology classification criteria, GCA-related events, and alternative diagnoses using data collected at all assessments. Proposed treatment data will be collected from participating clinicians after each test result is released, and classified as treatment for GCA (e.g. initiate/continue steroids) or not GCA (e.g. withdraw/rapid taper of steroids) to compare changes in proposed treatment and evaluate agreement with the reference diagnosis. Unit costs of resources used will be obtained from nationally published sources where available. Modelling will estimate the impact of diagnostic strategies on clinical outcomes (e.g. GCA complications and steroid related adverse events), their costs and impact on HRQoL beyond study follow-up and within study follow-up. Probabilities of events, their cost and impact will be obtained from study data, a systematic literature review, or in the absence of relevant data, by formal elicitation of expert opinion. Costs and benefits will be discounted at 3.5% (National Institute for Health and Care Excellence [NICE] guidance) and uncertainty (including modelling assumptions) subjected to probabilistic sensitivity analysis and scenario analysis.
SAMPLE SIZE:
A sample size of 402 patients provides 90% power at a 5% type I error rate to test the joint hypothesis that (i) US has greater sensitivity than biopsy (to detect an increase in sensitivity from 76% for biopsy (assuming a 0.24 false negative fraction based on 9-44% biopsy-negative GCA) to 87% sensitivity for US; and (ii) to detect specificity of US of no less than 0.83 based on an expected specificity of 0.96. This sample size will allow estimation of a one-sided rectangular confidence region for US false and true positive fractions, assuming 80% prevalence of GCA in patients having a biopsy for suspected GCA, with the sample size inflated (gamma=0.1) due to uncertainty in the proportion of cases/controls in a cohort design. We will actually recruit 430 cases to allow for possible drop-outs from the study. In addition we will recruit 270 individuals for training purposes, to allow each centre to learn the technique of temporal artery and axillary artery scanning. Each centre will collect 10 such individuals (training cases), who will be of similar age and gender as the study cohort, but who will not have temporal arteritis. This is very important in order to ensure that observers are trained to recognise the appearances seen in normal (non GCA arteries) especially patients with atherosclerosis. Further ultrasound training including a video exam (to identify images of both normal and abnormal features of GCA) and a 'hot' case assessment (scanning a patient with GCA) will be designed into the ultrasound training programme. In addition, we will provide adequate training days (e.g. 2 separate training days) when all observers will be trained formally by Dr Schmidt and other ultrasound experts to ensure adequate observer agreement. The first training day will be held prior to starting the recruitment of patients, and will be repeated after the first year.
PROJECT TIMETABLE:
Total: 48 months (UPDATED TO 60 MONTHS SEE BELOW) Month 1-6 Study materials/protocols prepared; Ethics and research governance approval complete; Centres trained, approved and ready to recruit.
Month 7-12 Recruitment monitoring report; Quality control report. Month 13-18 Recruitment monitoring report; Quality control report; Additional centres (if required) trained, approved and ready to recruit; Month 19-24 Recruitment monitoring report; Quality control report. Month 25-30 Recruitment monitoring report; Quality control report; Web-based US and biopsy assessment developed.
Month 31-36 Recruitment completed; Clinical vignettes (web-based) developed. Month 37-42 Follow-up completed; Inter-rater assessment of US and biopsy images analysis competed; Expert panel review of vignettes completed.
Month 43-48 Database cleaned and locked; Analysis completed; statistical analysis and economic modelling, report drafting and preparation of papers. Final report completed.
PLEASE NOTE: 12 MONTH EXTENSION WAS GRANTED BY THE FUNDER (NIHR HTA) IN SEPTEMBER 2012 TO EXTEND THE RECRUITMENT PERIOD FROM THE END OF DECEMBER 2012 TO END OF DECEMBER 2013 (A FURTHER 12 MONTHS).
TH END OF STUDY WILL NOW BE DECEMBER 2014
The study will be overseen by a Trial Steering Committee (TSC) and an independent Data Monitoring Committee (DMC)at least 1 meeting per year.
BIOBANK:
We will develop a biobank of tissue, serum, DNA and ultrasound video imaging of blood vessels in GCA. An important benefit of the primary protocol is that we can use the accumulated material for a number of related projects.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Suspected GCA | – | Procedure: Ultrasound of temporal and axillary arteries, Procedure: Temporal artery biopsyPatients who present with new onset of headache and suspected diagnosis of GCA. They will all require a temporal artery biopsy to assist in the diagnosis |
| Training cohort | – | Procedure: Ultrasound of temporal and axillary arteriesPatients with any condition or healthy volunteers who are willing to consent ot have their temporal and axillary arteries examined using ultrasound, for training purposes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Study cohort: Patients with suspected new giant cell arteritis Training cohort; patients or healthy volunteers willing to have temporal artery and axillary artery ultrasound examination
Key inclusion criteria (12 listed)
- A clinical suspicion of new diagnosis of GCA e.g. patients with a new onset of headache, scalp tenderness, with or without elevated CRP or ESR, jaw or tongue claudication with or without visual loss.
- The clinician decides that the patient requires an urgent temporal artery biopsy to determine whether or not the diagnosis is GCA.
- The patient agrees and provides NHS consent to undergo a temporal artery biopsy as part of standard care.
- Patients have been started on high dose glucocorticoids or will be started on high dose glucocorticoids.
- Patients must be willing to attend for an ultrasound scan of their temporal and axillary arteries.
Key exclusion criteria (11 listed)
- Previous diagnosis of GCA.
- Use of high dose glucocorticoid (>20mg prednisolone/day) for management of current suspected GCA for more than 7 days prior to the dates of the ultrasound and biopsy.
- Long term (>1 month) high dose (>20mg per day at any time) steroids for conditions other than PMR, within three months prior to study entry.
- Inability to give informed consent (either written consent or verbal assent from a relative or carer)
- Inability to undergo an ultrasound scans of the temporal and axillary arteries.
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 |
|---|---|---|
| Ultrasound of temporal and axillary arteriesAlso: Ultrasound scanStandardised assessment of temporal arteries and axillary arteries using high resolution ultrasound to detect halo, stenosis or occlusion | Procedure or surgery | Suspected GCA, Training cohort |
| Temporal artery biopsyAlso: Biopsy of temporal arteryBiopsy of temporal artery from symptomatic side | Procedure or surgery | Suspected GCA |
Primary outcome
To evaluate the diagnostic accuracy of ultrasound vs temporal artery biopsy for diagnosis of suspected GCA and to evaluate the cost-effectiveness (incremental cost per QALY) of ultrasound instead of biopsy in the diagnosis of GCA.
Time frame: Six months
13 secondary outcomes
To evaluate inter-observer agreement in the assessment of ultrasound and temporal artery biopsy
Time frame: Six months
To elicit expert views on the appropriateness of performing a biopsy following ultrasound using clinical vignettes
Time frame: 3 years
To evaluate the diagnostic accuracy (sensitivity and specificity) of the sequential diagnostic strategy as an alternative to temporal artery biopsy alone in the diagnosis of GCA
Time frame: 3 years
To evaluate the cost-effectiveness (incremental cost per QALY) of the diagnostic strategy of combined ultrasound and biopsy instead of biopsy alone in the diagnosis of GCA.
Time frame: 3 years
Specific adverse events measured at each assessment; daily and cumulative steroid dose; steroid side effects; and pain or dysaesthesia at the biopsy site.
Time frame: Six months
Evolution of an alternative diagnosis
Time frame: Six months
Negative predictive value of ultrasound in preventing the need for temporal artery biopsies.
Time frame: Six months
Cost analysis of performing a screening ultrasound examination plus biopsy as part of the diagnostic workup of all patients with suspected GCA; or of performing a screening ultrasound examination instead of biopsy; or of performing a screening ultrasound
Time frame: Six months
Cost analysis of performing a screening ultrasound examination instead of biopsy in cases with a very low probability of GCA as part of the diagnostic workup of all patients with suspected GCA.
Time frame: 3 years
Prediction of potential harm done to patients by over diagnosis or under diagnosis of GCA as a result of ultrasound use, either alone or in combination with biopsy
Time frame: 3 years
Value of axillary artery ultrasound scanning in contributing to the diagnosis of GCA.
Time frame: Six months
Analysis of proportion of patients with a biopsy positive halo, stenosis, or occlusion assessed by high resolution ultrasound
Time frame: 3 years
Presence of characteristic features of GCA on temporal artery biopsy in relation to clinical and ultrasound findings
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2015.
- Background: PubMed 2202311Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990 Aug;33(8):1122-8. doi: 10.1002/art.1780330810.
- Background: PubMed 16414971Smeeth L, Cook C, Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Ann Rheum Dis. 2006 Aug;65(8):1093-8. doi: 10.1136/ard.2005.046912. Epub 2006 Jan 13.
- Background: PubMed 18606086Borg FA, Salter VL, Dasgupta B. Neuro-ophthalmic complications in giant cell arteritis. Curr Allergy Asthma Rep. 2008 Jul;8(4):323-30. doi: 10.1007/s11882-008-0052-4.
- Derived from this study: PubMed 39817309Maughan RT, Macdonald-Dunlop E, Haroon-Rashid L, Sorensen L, Chaddock N, Masters S, Porter A, Peverelli M, Pericleous C, Hutchings A, Robinson J, Youngstein T, Luqmani RA, Mason JC, Morgan AW, Peters JE. Proteomic Profiling of the Large-Vessel Vasculitis Spectrum Identifying Shared Signatures of Innate Immune Activation and Stromal Remodeling. Arthritis Rheumatol. 2025 Jul;77(7):884-900. doi: 10.1002/art.43110. Epub 2025 Feb 27.
- Derived from this study: PubMed 28405470Goodfellow N, Morlet J, Singh S, Sabokbar A, Hutchings A, Sharma V, Vaskova J, Masters S, Zarei A, Luqmani R. Is vascular endothelial growth factor a useful biomarker in giant cell arteritis? RMD Open. 2017 Mar 29;3(1):e000353. doi: 10.1136/rmdopen-2016-000353. eCollection 2017.
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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.
Raashid A Luqmani, DM FRCP study chair
University of Oxford
Andrew Hutchings principal investigator
London School of Hygiene and Tropical Medicine
Mike Bradburn principal investigator
University of Sheffield
27 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Giant Cell Arteritis, run by University of Oxford at 27 sites in 5 countries.
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 12 inclusion and 11 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: finished, as of the sponsor's last update on 17 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United Kingdom, Germany, Ireland, Norway, Portugal. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the diagnostic accuracy of ultrasound vs temporal artery biopsy for diagnosis of suspected GCA and to evaluate the cost-effectiveness (incremental cost per QALY) of ultrasound instead of biopsy in the diagnosis of GCA. (time frame: Six months). 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 NCT00974883, which also lists 5 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 17 Jul 2015.