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

Sponsor

NHS Lothian (Other)

Overall Status

Recruiting

CT.gov ID

NCT05582967

Collaborator

University of Edinburgh (Other)

5,000

Enrollment

Locations

3.2

Anticipated Duration (Months)

200

Patients Per Site

63.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Dissection	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 Design

Study Type:

Observational

Anticipated Enrollment :

5000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Sep 26, 2022

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Royal United Hospital	Bath	United Kingdom
2	Bristol Royal Infirmary	Bristol	United Kingdom
3	North Bristol NHS Trust	Bristol	United Kingdom
4	Addenbrookes hospital	Cambridge	United Kingdom
5	Royal Infirmary of Edinburgh	Edinburgh	United Kingdom
6	St Johns Hospital	Edinburgh	United Kingdom
7	Frimley Health	Frimley	United Kingdom
8	Queen Elizabeth University Hospital	Glasgow	United Kingdom
9	Royal Alexandra Hospital	Glasgow	United Kingdom
10	James Paget University Hospital	Great Yarmouth	United Kingdom
11	Harrogate	Harrogate	United Kingdom
12	Raigmore	Inverness	United Kingdom
13	Queen Elizabeth Hospital NHS Foundation Trust	King's Lynn	United Kingdom
14	Victoria Hospital	Kirkcaldy	United Kingdom
15	Lewisham and Greenwich NHS Trust	Lewisham	United Kingdom
16	Luton & Dunstable University Hospital	Luton	United Kingdom
17	Wythenshawe Hospital	Manchester	United Kingdom
18	Milton Keynes Universoty Hospital NHS Foundation Trust	Milton Keynes	United Kingdom
19	Royal Victoria Infirmary	Newcastle	United Kingdom
20	Royal Oldham Hospital	Oldham	United Kingdom
21	John Radcliffe Hospital	Oxford	United Kingdom
22	Royal Glamorgan Hospital	Pontyclun	United Kingdom
23	Royal Berkshire NHS Foundation Trust	Reading	United Kingdom
24	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	United Kingdom
25	Wexham Park	Slough	United Kingdom