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

An Observational Cohort Study of People Attending the ED With Symptoms of Acute Aortic Syndrome (AAS)

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.

Study Overview

• Status: Completed
• Conditions: Aortic Dissection
• Intervention / Treatment: Other: Completion of focused Electronic Case Report Form

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.

• Study Type: Observational
• Enrollment (Actual): 5548

Contacts and Locations

Study Locations

• United Kingdom
  • Bath, United Kingdom
    • Royal United Hospital
  • Bristol, United Kingdom
    • Bristol Royal Infirmary
  • Bristol, United Kingdom
    • North Bristol NHS Trust
  • Cambridge, United Kingdom
    • Addenbrookes Hospital
  • Edinburgh, United Kingdom
    • Royal Infirmary of Edinburgh
  • Edinburgh, United Kingdom
    • St Johns Hospital
  • Frimley, United Kingdom
    • Frimley Health
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • Glasgow, United Kingdom
    • Royal Alexandra Hospital
  • Great Yarmouth, United Kingdom
    • James Paget University Hospital
  • Harrogate, United Kingdom
    • Harrogate
  • Inverness, United Kingdom
    • Raigmore
  • King's Lynn, United Kingdom
    • Queen Elizabeth Hospital NHS Foundation Trust
  • Kirkcaldy, United Kingdom
    • Victoria Hospital
  • Lewisham, United Kingdom
    • Lewisham and Greenwich NHS Trust
  • Luton, United Kingdom
    • Luton & Dunstable University Hospital
  • Manchester, United Kingdom
    • Wythenshawe Hospital
  • Milton Keynes, United Kingdom
    • Milton Keynes Universoty Hospital NHS Foundation Trust
  • Newcastle, United Kingdom
    • Royal Victoria Infirmary
  • Oldham, United Kingdom
    • Royal Oldham Hospital
  • Oxford, United Kingdom
    • John Radcliffe Hospital
  • Pontyclun, United Kingdom
    • Royal Glamorgan Hospital
  • Reading, United Kingdom
    • Royal Berkshire NHS foundation trust
  • Sheffield, United Kingdom
    • Sheffield Teaching Hospitals NHS Foundation Trust
  • Slough, United Kingdom
    • Wexham Park

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All people attending the Emergency Department (ED) with symptoms of possible AAS, including new-onset chest, back or abdominal pain, syncope or symptoms related to malperfusion.

Description

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.
• ≥16 years old

Exclusion Criteria:

• No symptoms of AAS.
• <16 years old

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrolment rate at each participating site	Number of participants during study period enrolled	30 days
Proportion of patients in whom the ED clinician thinks Acute Aortic Syndrome (AAS) is a possible differential who have confirmed AAS	Proportion of patients in whom the ED clinician thinks Acute Aortic Syndrome (AAS) is a possible differential who have confirmed AAS	30 days
Proportion of patients in whom ED clinician considers AAS NOT a possible differential who had confirmed AAS	Proportion of patients in whom ED clinician considers AAS NOT a possible differential who had confirmed AAS	30 days
Number of AAS patients not enrolled due to lack of clinical/research support	Number of AAS patients not enrolled due to lack of clinical/research support	30 days
CT angiogram (CTA) ordering and positivity rate	Number of CT angiograms ordered and the proportion that are positive scans	30 days
Test characteristics of clinical acumen	Test characteristics of clinical acumen (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Test characteristics of ADD-RS (Aortic Dissection Detection-Risk Score)	Test characteristics of Aortic Dissection Detection-Risk Score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Test characteristics Aorta score	Test characteristics of Aorta score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Test characteristics of Canadian guideline score	Test characteristics of Canadian guideline score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Test characteristics of Sheffield AAS decision rule	Test characteristics of Sheffield AAS decision rule (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Test characteristics of D-dimer	Test characteristics of D-dimer (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Median time from hospital presentation to imaging diagnosis and median time from symptom onset to hospital presentation (hours)	Median time from hospital presentation to imaging diagnosis and median time from symptom onset to hospital presentation (hours)	30 days
30-day mortality in proven AAS	30-day mortality in proven AAS	30 days
Proportion of alternative diagnoses found on CTA and final hospital diagnosis	Proportion of alternative diagnoses found on CTA and final hospital diagnosis	30 days
Number of patients not able to be enrolled with reason why not enrolled	Number of patients not able to be enrolled with reason why not enrolled	30 days

Collaborators and Investigators

• Sponsor: NHS Lothian
• Collaborators: University of Edinburgh
• Investigators: Principal Investigator: Rachel McLatchie, Accord Clinical Research

Publications and helpful links

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2022
• Primary Completion (Actual): January 21, 2023
• Study Completion (Actual): January 21, 2023

Study Registration Dates

• First Submitted: October 10, 2022
• First Submitted That Met QC Criteria: October 12, 2022
• First Posted (Actual): October 17, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Diagnosis; Emergency; Diagnostic accuracy; Aorta; Aortic Dissection
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Aneurysm; Aneurysm, Dissecting
• Other Study ID Numbers: AC22083; 22/PR/0807 (Other Identifier: Research Ethics Committee); 315948 (Other Identifier: IRAS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data may be shared on request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No