Temporal Artery Biopsy vs ULtrasound in Diagnosis of GCA (TABUL)
|First Received Date ICMJE||September 9, 2009|
|Last Updated Date||January 27, 2014|
|Start Date ICMJE||June 2010|
|Primary Completion Date||December 2013 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
||To evaluate the diagnostic accuracy (sensitivity and specificity) and cost effectiveness of ultrasound as an alternative to temporal artery biopsy for the diagnosis of GCA in patients referred for biopsy with suspected GCA. [ Time Frame: Six months ] [ Designated as safety issue: No ]|
|Change History||Complete list of historical versions of study NCT00974883 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Temporal Artery Biopsy vs ULtrasound in Diagnosis of GCA (TABUL)|
|Official Title ICMJE||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.
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.
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.
Outpatient and inpatient rheumatology and ophthalmology departments in 25 NHS trusts in the 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 EQ-5D, and adverse events. Baseline assessment will include retrospective assessment of symptoms and 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% (NICE guidance) and uncertainty (including modelling assumptions) subjected to probabilistic sensitivity analysis and scenario analysis.
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.
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.
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 Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Cohort
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Biospecimen||Retention: Samples With DNA
Temporal artery biopsy samples Serum Plasma White cells Video images of temporal and axillary arteries
|Sampling Method||Non-Probability Sample|
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
|Condition ICMJE||Giant Cell Arteritis|
|Study Group/Cohort (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||700|
|Estimated Completion Date||December 2014|
|Primary Completion Date||December 2013 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Inclusion Criteria: for the cohort study
For the training cases
Exclusion criteria: for the cohort study
For the training cases
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||Germany, Ireland, Norway, Portugal, United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT00974883|
|Other Study ID Numbers ICMJE||08/64/01, ISRCTN46280267|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Dr Raashid Luqmani Consultant Rheumatologist, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford|
|Study Sponsor ICMJE||University of Oxford|
|Information Provided By||University of Oxford|
|Verification Date||November 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP