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American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Diagnostic and Classification Criteria for Primary Systemic Vasculitis
Study Purpose
Vasculitis is group of diseases where inflammation of blood vessels is the common feature. Patients typically present with fever, fatigue, weakness and muscle and joint aches. These symptoms are very common among many different diseases, not just vasculitis. A clustering of other symptoms, physical examination findings, blood tests, radiology and biopsy help make the diagnosis. There are currently no criteria to help doctors make a diagnosis of vasculitis when a patient presents with these non specific symptoms and they are reliant on previous experience and disease definitions. One of the aims of this project is to develop diagnostic criteria for the primary systemic vasculitides (granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, Churg Strauss syndrome, polyarteritis nodosa, giant cell arteritis, Takayasu arteritis). We, the investigators, will do this by studying a large group of patients with vasculitis and comparing them to a large group of patients that present in a similar way, but do not have vasculitis. By comparing the 2 groups we will create a list of items to differentiate between vasculitis and 'vasculitis mimics'. We also aim to update the current classification criteria. Classification criteria are used to group patients into different types of vasculitis, once a diagnosis of vasculitis has been made, and are useful for studying patients in clinical trials with similar or identical diseases. The current classification criteria (American college of Rheumatology 1990 criteria) were developed 20 years ago, before the availability of some important diagnostic tests (e.g. antineutrophil cytoplasmic antibodies [ANCA]), and are now not consistent with some of the current disease definitions. Therefore to progress future research in vasculitis, it is important that the classification criteria are updated. We will recruit 260 patients with each of the 6 types of vasculitis and compare them with 1300 controls (patients with the 5 other types of vasculitis), in order to determine the optimal combination of symptoms, signs and investigations that classify each person into the appropriate group.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Observational |
Eligible Ages | 18 Years and Over |
Gender | All |
Inclusion Criteria for Classification criteria: 1. Adult patients aged >18 years. There is no upper age limit. 2. Ability to give informed consent. If the patient is unable to give informed consent as a result of death or physical incapacity, then informed assent from next of kin. 3. Presumed diagnosis of a primary systemic vasculitis. Exclusion criteria for classification criteria: 1. Patients < 18 years of age. 2. Inability to provide informed consent. 3. Hepatitis B or C 4. Co-morbidities that explain the clinical symptoms and signs on which the diagnosis of vasculitis is made. E.g. infection, tumour, other inflammatory condition, etc. Inclusion criteria for diagnostic criteria: 1. Adult patients aged >18 years. There is no upper age limit. 2. Ability to give informed consent. If the patient is unable to give informed consent as a result of death or physical incapacity, then informed assent from next of kin. 3. Suspected diagnosis of a primary systemic vasculitis Inclusion criteria for controls group for diagnostic criteria: 1. Adult patients aged >18 years. There is no upper age limit. 2. Ability to give informed consent. If the patient is unable to give informed consent as a result of death or physical incapacity, then informed assent from next of kin. 3. Patients presenting to secondary care with one of the following clinical presentations: I.Multi-system disease. Presentation of disease with at least 2 organs involved. II.Pulmonary-renal syndrome. Defined as haemoptysis / pulmonary haemorrhage with acute renal impairment. III.Acute renal failure IV.Acute respiratory distress. V.Chronic upper airways symptoms and signs. VI.Inflammatory polyarthritis. VII.Fever of unknown origin. VIII.Acute or chronic abdominal pain IX.Hypertension. X.Referred to secondary care with suspicion of vasculitis but confirmed not to have vasculitis. XII.New onset headache. XIII.Jaw or tongue pain. XIV.Sudden visual loss. XV.Limb claudication. XVI.Aortic aneurysm >5cm. Exclusion Criteria for diagnostic criteria: 1. Patients under the age of 18 2. Patient or next of kin unable or unwilling to provide informed consent or assent.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT01066208 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
|
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
University of Oxford |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Raashid A Luqmani, DM, FRCP(E)Peter Merkel, MD, MPHRichard Watts, DM, FRCP |
Principal Investigator Affiliation | University of Oxford, United KingdomUniversity of PennsylvaniaUniversity of East Anglia |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Other |
Overall Status | Recruiting |
Countries | Argentina, Australia, Austria, Belgium, Canada, China, Czech Republic, Denmark, Egypt, Finland, France, Germany, Hungary, India, Ireland, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Slovenia, Spain, Sri Lanka, Sweden, Switzerland, Turkey, United Kingdom, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Wegener's Granulomatosis, Microscopic Polyangiitis, Churg Strauss Syndrome, Polyarteritis Nodosa, Giant Cell Arteritis, Takayasu Arteritis |
Study Website: | View Trial Website |
The systemic vasculitides are a group of uncommon but important diseases whose prognosis has improved dramatically with the use of immunosuppressive therapy. However, long-term morbidity from recurrent disease flares, low-grade grumbling disease and/or accumulating damage from previous disease activity or drug therapy now characterise the long-term outlook for patients with vasculitis. There remains major controversy, and incompatibility between the ANCA-associated vasculitides: granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, and Churg Strauss Syndrome, as well as polyarteritis nodosa in the current classification criteria and disease definitions. Importantly, there are no diagnostic criteria for any of the primary systemic vasculitides. We propose to improve existing classification criteria for the primary systemic vasculitides. As a starting point will include the following diseases: granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), Churg Strauss syndrome (CSS), polyarteritis nodosa (PAN), giant cell arteritis (GCA) and Takayasu arteritis (TAK). We propose to develop and validate classification and diagnostic criteria for primary systemic vasculitis using the guidelines suggested by the Classification and Response Criteria Subcommittee of the American College of Rheumatology Committee on Quality Measures. For all patients, a detailed medical history, physical examination, laboratory tests (including ANCA), radiology (including angiography), biopsy results, treatment, Birmingham Vasculitis Activity Score (BVAS)version 3, Vasculitis Damage Index (VDI), will be collected. The exact list of items to be recorded will be determined by the expert panel at the start of the study. Classification criteria We will study a minimum of 100 patients (new and existing patients) prospectively within each currently defined disease category (GPA, CSS, MPA, PAN, GCA, TAK) for the development of the classification criteria. We anticipate the need to recruit 130 patients to account for misdiagnosis and dropout to achieve the target of 100 with the confirmed reference diagnosis. This will include patients that have vasculitis which are assumed to be related to ANCA but do not fulfil the current definitions of any of the diseases, and patients with large vessel vasculitis which do not fulfil current definition for GCA or TAK. Therefore new categories of disease may be created as part of this process and some of the current disease categories may be changed to include or exclude certain patients. The other diseases will be the controls. The same minimum number of patients will be used to validate the criteria. The 1st 100 patients with a formal reference diagnosis that are recruited for each disease will be used for development of the classification criteria; the next 100 consecutive patients recruited with a confirmed reference diagnosis for each disease will be used to validate the criteria. Again we anticipate the need to recruit 130 patients to account for misdiagnosis and dropout to achieve the 100 target. The majority of cases included will be the same as that used for the development of the diagnostic criteria. In the absence of an established gold standard, we propose to develop a reference standard. Clinical vignettes using clustering of clinical features and investigations will be constructed from actual cases by the steering group. An expert panel will then be asked to classify each vignette. Hypothetical changes will then be made to components of each clinical vignette and the expert panel will be asked to re classify the case. This process will be repeated multiple times in an attempt to determine what key clinical feature influence the expert panel to change the diagnosis. Using this data driven process, a construct of important clinical features for each disease will be determined by the expert panel. Using this new construct, patients will be classified by the expert panel. This will form the reference standard against which the new criteria will be tested. Diagnostic Criteria We propose to develop and validate diagnostic criteria for primary systemic vasculitis. Based on current disease categories we will include GPA, MPA, CSS, PAN, GCA and TAK (but this may change depending on whether new categories are created or existing categories merged as part of the classification criteria component). For the development of diagnostic criteria, we will study a minimum of 100 patients (will require approx 130 patients to allow for dropout and misdiagnosis) for each disease category. Assuming 6 disease categories, the majority of these 780 patients will have already been identified from the classification criteria component of the study and will be re used for the development and validation of diagnostic criteria. However, for the diagnostic criteria to be clinically relevant we will only include patients that are seen at the time of 1st presentation, therefore not all the 780 patients recruited for the classification criteria section of the study will be suitable, and we will need to recruit additional new patients for each of the types of vasculitis being studied. We will use a minimum of 400 context specific controls (patients that don't have vasculitis) for AAV and PAN that will cover the spectrum of different disease presentations and severity. In addition, we will recruit a minimum of 100 context specific controls for GCA and a similar number for TAK. Different control populations are needed for AAV, GCA and TAK as they have significantly different clinical presentations. In a similar manner to cases, we will recruit 30% more patients than the minimum required to account for misdiagnosis and drop out. The same minimum number of cases and controls will be needed to validate the criteria. The first half of the patients recruited would be used to develop the criteria, and the 2nd half to validate the criteria. We will allow inclusion of patients from previously studied prospective cohorts that meet all the appropriate inclusion / exclusion criteria and have had all the appropriate clinical information and mandatory investigation (to be defined later) recorded at time of their first presentation. This is to facilitate the recruitment of sufficient patients with PAN, CSS and TAK which are rare conditions. Statistical analysis We will follow the ACR recommended statistical methods for creating the classification criteria. Patients will have been classified into the different types of vasculitis according to the proposed EULAR/ACR schema by the expert panel or as a vasculitis mimic. The outcomes of interest are binary variables indicating whether or not a patient has been classified as having a particular type of vasculitis, such as GPA, MPA, etc. For each outcome, multivariable logistic regression modeling will be used to identify predictors of outcome based on the list of potential predictor variables described earlier. We will also explore the use of Classification And Regression Tree (CART) analysis. This is a tree-building technique ideally suited to the generation of clinical decision rules. Unlike conventional regression methods, patients are partitioned ("split") into different groups based on an exhaustive search of all possible predictor variables. The advantage of CART analysis over conventional methods is that it is non-parametric, so no assumptions are made about the underlying distribution of predictor variables. CART can handle many hundreds of possible predictor variables and can uncover complex interactions between predictors which may be difficult or impossible to uncover using traditional multivariate techniques that can suffer from model over fitting. In addition, clinicians generally do not think in terms of probability but rather in terms of categories, such as low versus high risk. Clinical decision rules generated using CART analysis are more likely to make clinical sense, and hence more likely to be followed in clinical practice. Once the best items are identified, the expert panel will decide on the best short list of items to be included in each criteria and also choose the most appropriate decision tree. This will provide the best content validity. The statistical methods to be used for diagnostic criteria will be very similar to that used for the classification criteria. The binary outcome for analysis is whether the person is a case or control (without vasculitis). We repeat the analyses for each of each type of vasculitis e.g. WG versus controls, then CSS versus controls etc
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Status
Recruiting
Address
Cedars-Sinai Medical Center, LA
Los Angeles, California, 90048
Status
Recruiting
Address
University of California, San Francisco
San Francisco, California, 94143-0500
Status
Recruiting
Address
University of Maryland
Baltimore, Maryland, 21201
Status
Recruiting
Address
Vasculitis Center, Boston University School of Medicine
Boston, Massachusetts, 02118
Status
Recruiting
Address
University of Michigan, Internal Medicine
Ann Arbor, Michigan, 48109
Status
Recruiting
Address
Mayo Clinic
Rochester, Minnesota, 55905
Status
Recruiting
Address
Dartmouth-Hitchcock Medical Centre, Lebanon, NH
Lebanon, New Hampshire, 03756
Status
Not yet recruiting
Address
New York University Langone Medical Centre
New York, New York, 10016
Status
Not yet recruiting
Address
University of North Carolina
Chapel Hill, North Carolina, 27599-7525
Status
Recruiting
Address
Cleveland Clinic
Cleveland, Ohio, 44195
Status
Recruiting
Address
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Status
Recruiting
Address
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
Status
Not yet recruiting
Address
University Medical Center
Salt Lake City, Utah, 84132-0002
International Sites
Status
Recruiting
Address
Hospital Interzonal San Juan Bautista
San Fernando del Valle de Catamarca, Catamarca,
Status
Recruiting
Address
Ramos Mejia Hospital, University of Buenos Aires
Buenos Aires, , C1221ADC
Status
Recruiting
Address
ANU Medical Centre
Canberra, Australian Capital Territory,
Status
Recruiting
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Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
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Recruiting
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Medical University Innsbruck
Innsbruck, ,
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Recruiting
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University Hospitals Leuven
Leuven, ,
Status
Recruiting
Address
University of Manitoba
Winnipeg, Manitoba, R3A 1M4
Status
Recruiting
Address
St Joseph's Healthcare
Hamilton, Ontario,
Status
Recruiting
Address
University of Ottawa
Ottawa, Ontario, K1N 6N5
Status
Recruiting
Address
Mount Sinai Hospital, Toronto
Toronto, Ontario, ON M5T 2S8
Status
Recruiting
Address
McGill University
Montreal, Quebec, H3A 0G4
Status
Recruiting
Address
Sherbrooke University Hospital Centre
Sherbrooke, Quebec, J1H 5N4
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Not yet recruiting
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University of Calgary
Calgary, ,
Status
Recruiting
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St Joseph's Healthcare London, Ontario
Ontario, ,
Status
Recruiting
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Peking Union Medical College Hospital, Beijing
Beijing, , 100032
Status
Recruiting
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General University Hospital, Prague
Prague, , 128 08
Status
Recruiting
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General University Hospital
Prague, ,
Status
Recruiting
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Rigshospitalet
Copenhagen, ,
Status
Recruiting
Address
Assiut University, Assiut University Hospitals
Assiut, , 71516
Status
Recruiting
Address
Cairo University, Kasr El Ainy Hospital
Cairo, ,
Status
Recruiting
Address
Helsinki University Central Hospital
Helsinki, ,
Status
Not yet recruiting
Address
Cochin Hospital, Université Paris-descartes
Paris, , 75679
Status
Recruiting
Address
Universitätsklinikum Jena
Jena, , 07743 Jena
Status
Recruiting
Address
University of Schleswig-Holstein
Luebeck, ,
Status
Recruiting
Address
Universitätsklinikum Münster
Münster, , 48149
Status
Recruiting
Address
Kreiskliniken Esslingen
Plochingen, , 73207
Status
Recruiting
Address
University Hospital Tübingen
Tübingen, , D-72076
Status
Recruiting
Address
University of Debrecen Medical and Health Science Center
Debrecen, , 4032
Status
Recruiting
Address
Chatrapathi Shahuji Maharaj Medical Center, Lucknow (IProcess)
Lucknow, Uttar Pradesh, 226003
Status
Recruiting
Address
Postgraduate Institute of Medical Education and Research, Chandigarh
Chandigarh, , Pin- 160 012
Status
Recruiting
Address
Nizam's Institute of Medical Sciences, Hyderabad
Hyderabad, , 500082
Status
Recruiting
Address
Medanta, Delhi
New Delhi, , 110024
Status
Recruiting
Address
Christian Medical College & Hospital, Vellore
Vellore, , 632 004
Status
Recruiting
Address
Cork University Hospital
Cork, ,
Status
Recruiting
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St. Vincent's University Hospital, Dublin
Dublin 4, ,
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Recruiting
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University of Parma
Parma, ,
Status
Recruiting
Address
Santa Maria Nuova Hospital, Reggio Emilia
Reggio Emilia, , 42123
Status
Recruiting
Address
Arcispedale Santa Maria Nuova
Reggio Emilia, ,
Status
Recruiting
Address
Kameda Medical Centre, Kamogawa
Kamogawa City, Chiba prefecture, 296-8602
Status
Recruiting
Address
Tsukuba University Hospital
Tsukuba, Ibaraki Prefecture, 305-8576
Status
Recruiting
Address
Miyazaki University Hospital
Miyazaki City, Miyazaki Prefecture, 889-1692
Status
Recruiting
Address
Saitama Medical University
Kawagoe, Saitama Prefecture, 350-8550
Status
Recruiting
Address
Kyorin University Hospital
Mitaka, Tokyo Prefecture, 181-8611
Status
Recruiting
Address
Chiba University
Chiba, , 260-8670
Status
Recruiting
Address
Kagawa University Hospital
Kagawa, , 761-0793
Status
Recruiting
Address
St. Marianna University Hospital
Kanagawa, , 216-8511
Status
Recruiting
Address
Kanazawa University Hospital
Kanazawa, , 920-8641
Status
Recruiting
Address
Okayama University Hospital
Okayama, , 700-8558
Status
Recruiting
Address
Juntendo University Koshigaya Hospital
Saitama, , 343-0032
Status
Recruiting
Address
Jichi Medical University Hospital
Tochigi-ken, , 3311-1 Yakushiji
Status
Recruiting
Address
University Tokyo Hospital
Tokyo, , 113-8655
Status
Recruiting
Address
Seoul National University Hospital
Seoul, , 110-744
Status
Recruiting
Address
Instituto Nacional de Enfermedades Respiratorias
Mexico City, , 14000
Status
Recruiting
Address
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, ,
Status
Not yet recruiting
Address
VU University Medical Center
Amsterdam, , 6Z 165
Status
Recruiting
Address
University Medical Center Groningen
Groningen, , 30.001
Status
Recruiting
Address
University of Otago, Christchurch
Christchurch, Canterbury, 8011
Status
Recruiting
Address
Auckland District Health Board
Auckland, ,
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Not yet recruiting
Address
Waitemata District Health Board, North Shore Hospital
Auckland, ,
Status
Recruiting
Address
Waikato District Health Board
Hamilton, , 3240
Status
Recruiting
Address
Hospital of Southern Norway
Kristiansand, , Post box 416, 4605
Status
Recruiting
Address
The University Hospital of Northern Norway, Tromsø
Tromsø, , 9038
Status
Recruiting
Address
University of Jagiellonian
Kraków, , 31-007
Status
Recruiting
Address
Hospital Garcia de Orta, Almada
Almada, ,
Status
Recruiting
Address
Santa Maria Hospital, Lisbon
Lisbon, , 1649-035
Status
Recruiting
Address
Hospital Santo Antonio, Porto
Porto, , 4099 - 001
Status
Recruiting
Address
First Moscow State Medical University
Moscow, , 119991
Status
Recruiting
Address
University Medical Centre Ljubljana
Ljubljana, , 1000
Status
Recruiting
Address
Clinic Barcelona Hospital Universitari
Barcelona, Catalonia,
Status
Recruiting
Address
University of Colombo
Columbo 8, ,
Status
Recruiting
Address
Lund University
Lund, , SE-221 85
Status
Not yet recruiting
Address
Karolinska Institute, Stockholm
Stockholm, , 141 86
Status
Recruiting
Address
Linköping University
Stockholm, , 581 83
Status
Not yet recruiting
Address
Umeå University
Umeå, , 901 85
Status
Not yet recruiting
Address
Uppsala University Hospital
Uppsala, , 751 85
Status
Recruiting
Address
University Hospital Basel
Basel, , 4031
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Not yet recruiting
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Immunologie-Zentrum Zurich
Zurich, ,
Status
Recruiting
Address
Hacettepe University
Ankara, ,
Status
Recruiting
Address
Istanbul University, Cerrahpasa Medical School
Istanbul, , 34098
Status
Recruiting
Address
Marmara University Medical School
Istanbul, , 34668
Status
Recruiting
Address
Fatih University Medical Faculty
Istanbul, , 34844
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Not yet recruiting
Address
Haydarpasa Education and Research Hospital
Istanbul, ,
Status
Recruiting
Address
Istanbul University, Istanbul Medical School
Istanbul, ,
Status
Recruiting
Address
North Cumbria University Hospitals, The Cumberland Infirmary
Carlisle, Cumbria, CA2 7HY
Status
Recruiting
Address
Basildon and Thurrock University Hospitals NHS Foundation Trust
Basildon, Essex, SS16 5NL
Status
Recruiting
Address
Queen's Hospital
Romford, Essex, RM7 0AG
Status
Recruiting
Address
Southend University Hospital NHS Trust
Westcliff-on-Sea, Essex, SS0 0RY
Status
Recruiting
Address
NHS Fife, Whyteman's Brae Hospital, Windygates
Kirkcaldy, Fife, KY8 5PR
Status
Recruiting
Address
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB25 2ZN
Status
Recruiting
Address
NHS Greater Glasgow & Clyde, Gartnavel Hospital
Glasgow, Scotland, G12 8TA
Status
Recruiting
Address
Ipswich Hospital NHS Trust
Ipswich, Suffolk,
Status
Recruiting
Address
Epsom and St Helier University Hospitals NHS Trust
Carshalton, Surrey, SM5 1AA
Status
Recruiting
Address
University of Birmingham
Birmingham, ,
Status
Recruiting
Address
Addenbrooke's Hospital
Cambridge, ,
Status
Recruiting
Address
Dudley Group of Hospitals, NHS FT
Dudley, , DY1 2HQ
Status
Recruiting
Address
Imperial College Healthcare NHS Trust, Hammersmith Hospital
London, , W12 0HS
Status
Recruiting
Address
University of Manchester, Manchester Royal Infirmary
Manchester, , M13 9WL
Status
Recruiting
Address
Norfolk and Norwich University Hospital
Norwich, , NR4 7UY
Status
Recruiting
Address
Nottingham University Hospitals NHS Trust (QMC)
Nottingham, , NG7 2UH
Status
Recruiting
Address
Nuffield Orthopaedic Centre
Oxford, , OX3 7LD
Status
Recruiting
Address
Oxford University Hospitals NHS Trust (The Churchill Hospital)
Oxford, , OX3 7LE
Status
Recruiting
Address
Royal Berkshire NHS Trust
Reading, , RG1 5AN
Status
Recruiting
Address
Heatherwood & Wexham Park Hospitals NHS Foundation Trust
Slough, , SL2 4HL
Status
Withdrawn
Address
Southampton University Hospitals NHS Trust
Southampton, , SO16 6YD
Site Contact
Status
Recruiting
Address
York Hospital NHS Foundation Trust
York, , YO31 8HE