Clinical trial NCT05582967: The DAShED (Diagnosis of Aortic Syndrome in the ED) Study
Official title: An Observational Cohort Study of People Attending the ED With Symptoms of Acute Aortic Syndrome (AAS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Aortic Dissection
Keywords: Aortic Dissection
Diagnostic accuracy
Aorta
Emergency
Diagnosis
Lead sponsor: NHS Lothian
Sponsor class: OTHER_GOV
Collaborators: name: University of Edinburgh
First posted: 2022-10-17
Enrollment: 5548
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Enrolment rate at each participating site
timeFrame: 30 days
measure: Proportion of patients in whom the ED clinician thinks Acute Aortic Syndrome (AAS) is a possible differential who have confirmed AAS
timeFrame: 30 days
measure: Proportion of patients in whom ED clinician considers AAS NOT a possible differential who had confirmed AAS
timeFrame: 30 days
measure: Number of AAS patients not enrolled due to lack of clinical/research support
timeFrame: 30 days
measure: CT angiogram (CTA) ordering and positivity rate
timeFrame: 30 days
measure: Test characteristics of clinical acumen
timeFrame: 30 days
measure: Test characteristics of ADD-RS (Aortic Dissection Detection-Risk Score)
timeFrame: 30 days
measure: Test characteristics Aorta score
timeFrame: 30 days
measure: Test characteristics of Canadian guideline score
timeFrame: 30 days
measure: Test characteristics of Sheffield AAS decision rule
timeFrame: 30 days
measure: Test characteristics of D-dimer
timeFrame: 30 days
measure: Median time from hospital presentation to imaging diagnosis and median time from symptom onset to hospital presentation (hours)
timeFrame: 30 days
measure: 30-day mortality in proven AAS
timeFrame: 30 days
measure: Proportion of alternative diagnoses found on CTA and final hospital diagnosis
timeFrame: 30 days
measure: Number of patients not able to be enrolled with reason why not enrolled
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Cambridge
country: United Kingdom
facility: Addenbrookes hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Edinburgh
country: United Kingdom
facility: St Johns Hospital
city: Frimley
country: United Kingdom
facility: Frimley Health
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: Glasgow
country: United Kingdom
facility: Royal Alexandra Hospital
city: Great Yarmouth
country: United Kingdom
facility: James Paget University Hospital
city: Harrogate
country: United Kingdom
facility: Harrogate
city: Inverness
country: United Kingdom
facility: Raigmore
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital NHS Foundation Trust
city: Kirkcaldy
country: United Kingdom
facility: Victoria Hospital
city: Lewisham
country: United Kingdom
facility: Lewisham and Greenwich NHS Trust
city: Luton
country: United Kingdom
facility: Luton & Dunstable University Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes Universoty Hospital NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Royal Victoria Infirmary
city: Oldham
country: United Kingdom
facility: Royal Oldham Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Pontyclun
country: United Kingdom
facility: Royal Glamorgan Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Slough
country: United Kingdom
facility: Wexham Park
Study officials:
affiliation: Accord Clinical Research
name: Rachel McLatchie
role: PRINCIPAL_INVESTIGATOR
References: