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

Aortic Dissection Clinical Trial

— DAShED  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05582967
• Other study ID #: AC22083
• Secondary ID: 22/PR/0807315948
• Status: Completed
• Start date: September 26, 2022
• Est. completion date: January 21, 2023

Study information

• Verified date: October 2022
• Source: NHS Lothian
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 5548
• Est. completion date: January 21, 2023
• Est. primary completion date: January 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm, Dissecting
• Aortic Dissection

Intervention

Other:
• Completion of focused Electronic Case Report Form
All patients will have a focussed Electronic Case Report Form completed collecting information around Presenting complaint, Past Medical History, Family History, Physical Examination findings, and Investigations.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
NHS Lothian	University of Edinburgh

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Enrolment rate at each participating site	Number of participants during study period enrolled	30 days
Primary	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
Primary	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
Primary	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
Primary	CT angiogram (CTA) ordering and positivity rate	Number of CT angiograms ordered and the proportion that are positive scans	30 days
Primary	Test characteristics of clinical acumen	Test characteristics of clinical acumen (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Primary	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
Primary	Test characteristics Aorta score	Test characteristics of Aorta score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Primary	Test characteristics of Canadian guideline score	Test characteristics of Canadian guideline score (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Primary	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
Primary	Test characteristics of D-dimer	Test characteristics of D-dimer (i.e. sensitivity, specificity, positive predictive value, negative predictive value)	30 days
Primary	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
Primary	30-day mortality in proven AAS	30-day mortality in proven AAS	30 days
Primary	Proportion of alternative diagnoses found on CTA and final hospital diagnosis	Proportion of alternative diagnoses found on CTA and final hospital diagnosis	30 days
Primary	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

External Links

•   Study website