Temporal Artery Biopsy vs ULtrasound in Diagnosis of GCA (TABUL)

NCT00974883 | Completed DMC

• 2 other identifiers: 08/64/01ISRCTN46280267
• Study Type: observational
• Target: 880
• Locations: 5 countries
• Sites: 27

Brief 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. 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.

Conditions

Giant Cell Arteritis

Keywords

ultrasound; GCA; temporal arteritis; biopsy

Outcome Measures

Primary Outcomes (1)

• 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.

  Six months

Secondary Outcomes (13)

• To evaluate inter-observer agreement in the assessment of ultrasound and temporal artery biopsy

  Six months

• To elicit expert views on the appropriateness of performing a biopsy following ultrasound using clinical vignettes

  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

  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.

  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.

  Six months

Study Arms (2)

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

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

Procedure: Ultrasound of temporal and axillary arteries

Interventions

Ultrasound of temporal and axillary arteries PROCEDURE

Standardised assessment of temporal arteries and axillary arteries using high resolution ultrasound to detect halo, stenosis or occlusion

Also known as: Ultrasound scan

Suspected GCA; Training cohort

Temporal artery biopsy PROCEDURE

Biopsy of temporal artery from symptomatic side

Also known as: Biopsy of temporal artery

Suspected GCA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University of Oxford: lead
• University of Sheffield: collaborator
• Mid and South Essex NHS Foundation Trust: collaborator
• Nuffield Orthopaedic Centre NHS Trust: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• The Leeds Teaching Hospitals NHS Trust: collaborator
• University of Bristol: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Medical Center for Rheumatology Berlin-Buch: collaborator

Study Sites (27)

Universitätsklinikum Jena

Jena, 07743 Jena, Germany

Location

St Vincent's University Hospital

Dublin, Dublin 4, Ireland

Location

Hospital of Southern Norway

Kristiansand, Post box 416, 4605, Norway

Location

Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Nuffield Orthopaedic Centre NHS Trust

Oxford, Oxfordshire, OX3 7LD, United Kingdom

Location

John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Stoke Mandeville Hospital

Aylesbury, HP21 8AL, United Kingdom

Location

Musgrave Park Hospital

Belfast, BT0 7JB, United Kingdom

Location

City Hospital Birmingham

Birmingham, B18 7QH, United Kingdom

Location

West Suffolk NHS Foundation Trust

Bury St Edmunds, IP33 2QZ, United Kingdom

Location

Derbyshire Royal Infirmary

Derby, DE1 2QY, United Kingdom

Location

Dudley Group of Hospitals

Dudley, DY1 2HY, United Kingdom

Location

Gateshead Health NHS Foundation Trust

Gateshead, NE9 6SX, United Kingdom

Location

James Paget University Hospitals NHS Foundation Trust

Great Yarmouth, NR31 6LA, United Kingdom

Location

Princess Alexandra Hospital

Harlow, Essex, CM20 1QX, United Kingdom

Location

Leeds University NHS Trust

Leeds, LS7 4SA, United Kingdom

Location

James Cook University Hospital,

Middlesbrough, United Kingdom

Location

Northampton Hospital

Northampton, United Kingdom

Location

Norfolk and Norwich Hospiital

Norwich, NR4 7UY, United Kingdom

Location

Queens Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

University of Oxford

Oxford, OX1 3RE, United Kingdom

Location

The Pennine Acute Hospitals NHS Trust

Pennine Rheumatology Centre, Rochdale Infirmary, OL12 0NB, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, PO6 3LY, United Kingdom

Location

Royal Berkshire

Reading, RG1 5AN, United Kingdom

Location

Queens Hospiital

Romford, RM7 0BE, United Kingdom

Location

Southend University Hospital

Southend, SSO 0EF, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 2202311 BACKGROUND

• Smeeth 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.

  PMID: 16414971 BACKGROUND

• Borg 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.

  PMID: 18606086 BACKGROUND

• Goodfellow 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.

  PMID: 28405470 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Temporal artery biopsy samples Serum Plasma White cells Video images of temporal and axillary arteries

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

High-Energy Shock Waves

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Raashid A Luqmani, DM FRCP

  University of Oxford

  STUDY CHAIR

• Andrew Hutchings

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

• Mike Bradburn

  University of Sheffield

  PRINCIPAL INVESTIGATOR

• Bhaskar Dasgupta

  University Hospital Southend

  PRINCIPAL INVESTIGATOR

• Allan Wailoo

  University of Sheffield

  PRINCIPAL INVESTIGATOR

• John Salmon

  John Radcliffe Hospital, Oxford

  PRINCIPAL INVESTIGATOR

• Eugene McNally

  Nuffield Orthopaedic Centre Oxford

  PRINCIPAL INVESTIGATOR

• William Hamilton

  University of Bristol

  PRINCIPAL INVESTIGATOR

• Colin Pease

  Leeds General Infirmary

  PRINCIPAL INVESTIGATOR

• Brendan McDonald

  John Radcliffe Hospital, Oxford

  PRINCIPAL INVESTIGATOR

• Konrad Wolfe

  University Hospital Southend

  PRINCIPAL INVESTIGATOR

• Wolfgang Schmidt

  Medical Centre for Rheumatology Berlin-Buch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2009
• First Posted: September 10, 2009
• Study Start: June 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2014
• Last Updated: July 17, 2015

Record last verified: 2015-07

Locations

DE (1); NO (1); PT (1); IE (1); GB (23)