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The DAShED (Diagnosis of Aortic Syndrome in the ED) Study

Completed
Conditions
Aortic Dissection
Registration Number
NCT05582967
Lead Sponsor
NHS Lothian
Brief Summary

Acute aortic syndrome (AAS) is a life-threatening emergency condition affecting the upper aorta affecting \~4000 people in the (United Kingdom; UK) a year with an ED misdiagnosis rate as high as 38%. Previous research has identified several strategies combining clinical probability scoring with blood tests (D-Dimer) to rule out the condition but when applied to a large population (ED) with relatively low numbers of actual cases, these result in a high rate of computed tomographic angiography (CTA) scanning. Current guidelines reflect the uncertainty of existing evidence.

This study, the first phase of three, aims to describe the characteristics of ED attendances with possible AAS, to determine the service implications of using different diagnostic strategies and inform future research. The investigators plan to recruit all ED attendances with possible AAS over a 1-4 week period. The investigators plan a prospective and retrospective approach to data collection adopting a waived-consent strategy with endpoint measures describing the characteristics of patients presenting with possible AAS.

Detailed Description

AAS is a life-threatening emergency condition which presents to the ED. Around 4,000 people suffer per year in the UK \[1\], many not receiving timely diagnosis and treatment. 25% of patients are not diagnosed until 24 hours after arriving in the ED due to the varied nature of presentation \[2\]. Chest pain is the most common presenting symptom of AAS (80%) although back pain (40%) and abdominal pain are not uncommon \[1\]. These symptoms account for over 2 million ED attendances per year in England \[National Health Service; NHS Digital A\&E 2021\] and are overwhelmingly due to causes other than AAS. The estimated incidence of AAS is 1 in every 980 ED attendances with atraumatic chest pain \[3\], thus creating a substantial diagnostic challenge.

Prognosis is best when patients are treated early, and mortality increases 2% per hour of delay. \[4\] The misdiagnosis rate during the initial ED visit for AAS is estimated to be between 1 in 3 to 1 in 7 AASs \[5\], leading to worse outcomes \[6,7\] whilst CTA over testing leads to diagnostic yields as low as 2-3%. \[2,8\]. CTA scanning of the aorta has high sensitivity and specificity for diagnosing AAS, but an unrestricted CT strategy will incur significant costs, has ionising radiation risks, resource implications, CT delays for non-AAS patients and the burden of 'incidentalomas'.

Clinicians therefore need to use CTA selectively but there is no validated scoring system to help this decision. Several have been proposed \[1, 9-14\] including the ADD-RS score, the Canadian clinical practice guideline Clinical Decision Aid \[13\], the AORTAs score \[14\] and the Sheffield score \[unpublished\]. D-Dimer has been suggested as a rule-out biomarker in low pre-test probability patients (95-98% sensitivity) \[15,16\] and has been incorporated into the Aortic Dissection Detection-Risk Stratification (ADD-RS) score to reduce CTA rate in low pre-test probability patients. None have been studied in truly undifferentiated ED populations, or in the UK where CTA threshold is different compared to North America. It is currently unclear whether any have sufficient sensitivity to be acceptable to clinicians, which is the most accurate, and whether they are likely to lead to CTA and D-Dimer over testing. Assessment of CTA rate and CT positivity has also not previously been studied. The Royal College of Emergency Medicine has recently released a national guideline advocating any patient with an ADD-RS score of \>=1 (no D-dimer incorporated) should have a CT aorta performed (unless other cause for symptoms identified and evidenced). The recommendation is not based on UK-validated clinical evidence, however, and clinical impacts of the recommendation are yet to be seen.

In view of these diagnostic challenges, the investigators aim in our programme of work to ultimately to assess which of the four aforementioned clinical decision tools is most effective, assess external validity, and assess clinical impact. This study (Phase 1; DAShED) will involve prospective data collection on all characteristics of four different risk scores, in addition to evaluation of patient characteristics, potential CT aorta rates with different strategies, and enrolment rates at participating sites. This will inform Phase 2, which will involve full interventional external validation study of the decision aid(s) selected in Phase 1 (including biomarker collection); the main objective being to select the score to subject to assessment of clinical impact (intervention step-wedge trial) in Phase 3.

This is an observational cohort study of all people attending the ED with symptoms of possible AAS, including new-onset chest, back or abdominal pain, syncope or symptoms related to malperfusion.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
5548
Inclusion Criteria
  • People attending the ED with symptoms of AAS, including those with new-onset chest, back or abdominal pain, syncope or symptoms related to malperfusion.
  • β‰₯16 years old
Read More
Exclusion Criteria
  • No symptoms of AAS.
  • <16 years old
Read More

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Median time from hospital presentation to imaging diagnosis and median time from symptom onset to hospital presentation (hours)30 days

Median time from hospital presentation to imaging diagnosis and median time from symptom onset to hospital presentation (hours)

Enrolment rate at each participating site30 days

Number of participants during study period enrolled

Number of AAS patients not enrolled due to lack of clinical/research support30 days

Number of AAS patients not enrolled due to lack of clinical/research support

Test characteristics Aorta score30 days

Test characteristics of Aorta score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)

Test characteristics of Canadian guideline score30 days

Test characteristics of Canadian guideline score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)

Proportion of patients in whom the ED clinician thinks Acute Aortic Syndrome (AAS) is a possible differential who have confirmed AAS30 days

Proportion of patients in whom the ED clinician thinks Acute Aortic Syndrome (AAS) is a possible differential who have confirmed AAS

CT angiogram (CTA) ordering and positivity rate30 days

Number of CT angiograms ordered and the proportion that are positive scans

Test characteristics of Sheffield AAS decision rule30 days

Test characteristics of Sheffield AAS decision rule (i.e. sensitivity, specificity, positive predictive value, negative predictive value)

Proportion of patients in whom ED clinician considers AAS NOT a possible differential who had confirmed AAS30 days

Proportion of patients in whom ED clinician considers AAS NOT a possible differential who had confirmed AAS

Test characteristics of clinical acumen30 days

Test characteristics of clinical acumen (i.e. sensitivity, specificity, positive predictive value, negative predictive value)

Test characteristics of D-dimer30 days

Test characteristics of D-dimer (i.e. sensitivity, specificity, positive predictive value, negative predictive value)

30-day mortality in proven AAS30 days

30-day mortality in proven AAS

Proportion of alternative diagnoses found on CTA and final hospital diagnosis30 days

Proportion of alternative diagnoses found on CTA and final hospital diagnosis

Test characteristics of ADD-RS (Aortic Dissection Detection-Risk Score)30 days

Test characteristics of Aortic Dissection Detection-Risk Score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)

Number of patients not able to be enrolled with reason why not enrolled30 days

Number of patients not able to be enrolled with reason why not enrolled

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (25)

Luton & Dunstable University Hospital

πŸ‡¬πŸ‡§

Luton, United Kingdom

Royal United Hospital

πŸ‡¬πŸ‡§

Bath, United Kingdom

Bristol Royal Infirmary

πŸ‡¬πŸ‡§

Bristol, United Kingdom

North Bristol NHS Trust

πŸ‡¬πŸ‡§

Bristol, United Kingdom

Addenbrookes hospital

πŸ‡¬πŸ‡§

Cambridge, United Kingdom

Frimley Health

πŸ‡¬πŸ‡§

Frimley, United Kingdom

St Johns Hospital

πŸ‡¬πŸ‡§

Edinburgh, United Kingdom

Royal Infirmary of Edinburgh

πŸ‡¬πŸ‡§

Edinburgh, United Kingdom

James Paget University Hospital

πŸ‡¬πŸ‡§

Great Yarmouth, United Kingdom

Queen Elizabeth University Hospital

πŸ‡¬πŸ‡§

Glasgow, United Kingdom

Royal Alexandra Hospital

πŸ‡¬πŸ‡§

Glasgow, United Kingdom

Victoria Hospital

πŸ‡¬πŸ‡§

Kirkcaldy, United Kingdom

Lewisham and Greenwich NHS Trust

πŸ‡¬πŸ‡§

Lewisham, United Kingdom

Harrogate

πŸ‡¬πŸ‡§

Harrogate, United Kingdom

Raigmore

πŸ‡¬πŸ‡§

Inverness, United Kingdom

Queen Elizabeth Hospital NHS Foundation Trust

πŸ‡¬πŸ‡§

King's Lynn, United Kingdom

Milton Keynes Universoty Hospital NHS Foundation Trust

πŸ‡¬πŸ‡§

Milton Keynes, United Kingdom

Wythenshawe Hospital

πŸ‡¬πŸ‡§

Manchester, United Kingdom

Royal Oldham Hospital

πŸ‡¬πŸ‡§

Oldham, United Kingdom

John Radcliffe Hospital

πŸ‡¬πŸ‡§

Oxford, United Kingdom

Royal Victoria Infirmary

πŸ‡¬πŸ‡§

Newcastle, United Kingdom

Royal Berkshire NHS Foundation Trust

πŸ‡¬πŸ‡§

Reading, United Kingdom

Royal Glamorgan Hospital

πŸ‡¬πŸ‡§

Pontyclun, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust

πŸ‡¬πŸ‡§

Sheffield, United Kingdom

Wexham Park

πŸ‡¬πŸ‡§

Slough, United Kingdom

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