18F Sodium Fluoride PET/CT in Acute Aortic Syndrome (FAASt)

The purpose of this study is to determine whether Sodium Fluoride imaging (using Positron Emission Tomography-Computed Tomography - PET-CT) is able to predict disease progression in acute aortic syndrome.

Study Overview

• Status: Completed
• Conditions: Aortic Dissection; Acute Aortic Syndrome; Penetrating Aortic Ulcer; Intramural Hematoma
• Intervention / Treatment: Diagnostic test: 18F Sodium Fluoride Positron Emission Tomography / Computed Tomography; Diagnostic test: CT Aortic Angiogram; Diagnostic test: Aortic MRI

Detailed Description

Acute Aortic Syndrome encompasses multiple aortopathies, including aortic dissection, intramural haematoma and penetrating aortic ulcers. Acute aortic syndrome has a three year mortality approaching 25%. To date, other than the initial aortic diameter, there are no accurate methods of establishing the risk of disease progression in patients with acute aortic syndrome.

In vascular disease, microcalcification occurs in response to necrotic inflammation. Using computed tomography and positron emission tomography (PET-CT), early microcalcification can be identified using uptake of the radiotracer 18F-sodium fluoride. This can identify high risk-lesions in the aorta, coronary and carotid arteries, and appears to be indicative of necrotic and heavily inflamed tissue. In abdominal aortic aneurysms, 18F-sodium fluoride binding predicts aortic expansion and the risk of aneurysm rupture or requirement for surgical repair.

The study investigators, therefore, propose to evaluate the ability of 18F-sodium fluoride to identify regions of necrotic inflammation in acute aortic syndrome to predict aortic expansion and disease progression.

Control patients with a normal calibre aorta will be recruited from the National Abdominal Aortic Aneurysm Screening Programme and Vascular Out-Patient Clinics. Patients with acute aortic syndrome and chronic aortic disease will undergo clinical assessments and 18F Sodium Fluoride PET/CT scans at baseline and 12-months. Clinical follow-up will continue for up to 3 years from recruitment.

• Study Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants with acute aortic syndrome will be recruited from emergency hospital admissions. Participants with chronic aortic disease will be recruited from out-patient clinics and thoracic aortic surveillance programmes. Healthy volunteers will be recruited from the national abdominal aortic aneurysm screening service and vascular out-patient department clinics.

Description

INCLUSION CRITERIA:

Patients with Acute Aortic Syndrome or Chronic Aortic Disease:

• A diagnosis of acute aortic syndrome as defined as per the European Society of Cardiology guidelines on the management of aortic disease a compatible clinical presentation with CT or magnetic resonance imaging confirming acute aortic syndrome.
• Adults over the age of 25 years
• Participants who have had previous open or thoracic endovascular aortic repair (TEVAR) are eligible to participate in the study.

Healthy Controls:

• No previous diagnosis of aortic disease
• Over the age of 55 years

EXCLUSION CRITERIA:

• The inability of patients to undergo PET/CT scanning
• Chronic kidney disease (eGFR ≤ 30 mL/min/1.73 m2)
• Major or untreated cancer
• Pregnancy
• Allergy or contra-indication to iodinated contrast
• Inability or unwillingness to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No Aortic Disease; Participants with normal calibre aortae and no prior diagnosis of acute aortic syndrome	Diagnostic test: 18F Sodium Fluoride Positron Emission Tomography / Computed Tomography; PET scan using the 18F-Sodium Fluoride radiotracer followed by an attenuation correction CT scan; Diagnostic test: Aortic MRI; Aortic MRI to assess aortic morphology and contextualise PET scan
Acute Aortic Syndrome; Participants presenting acutely with a diagnosis of acute aortic syndrome as defined in the European Society of Cardiology guidelines: a compatible clinical presentation with CT or magnetic resonance imaging confirming acute aortic syndrome.	Diagnostic test: 18F Sodium Fluoride Positron Emission Tomography / Computed Tomography; PET scan using the 18F-Sodium Fluoride radiotracer followed by an attenuation correction CT scan; Diagnostic test: CT Aortic Angiogram; CT scan to assess aortic morphology and contextualise PET scan
Chronic Aortic Disease; Participants with an established diagnosis of acute aortic syndrome.	Diagnostic test: 18F Sodium Fluoride Positron Emission Tomography / Computed Tomography; PET scan using the 18F-Sodium Fluoride radiotracer followed by an attenuation correction CT scan; Diagnostic test: CT Aortic Angiogram; CT scan to assess aortic morphology and contextualise PET scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aortic diameter	Maximum cross-sectional aortic diameter	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	All-cause mortality	24 months
18F Sodium Fluoride uptake in the aorta	18F Sodium Fluoride binding in the aorta will be measured from PET/CT scans performed at recruitment and at 12 months follow-up. Uptake will be quantified in Standardised Uptake Values and as a tissue to background ratios.	12 months
Hospital admissions	The requirement for hospital admission	24 months
Surgical Intervention	Requirement for surgical intervention during follow-up period	24 months
Change in renal function	Creatinine change during the follow-up period	24 months
Short Form-12 (SF12) questionnaire score	The SF12 is a validated, self reported quality of life assessment questionnaire. It consists of 12 questions that measure functional and mental well-being. Scores range from 12 to 47.	24 months
Disease related survival	Disease related survival	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Co-localisation of 18F-Sodium Fluoride with histological changes in aortic tissue	Uptake of 18F-Sodium Fluoride will be identified on PET-CT scans that are acquired as part of the study visit. This will be compared with histological changes in aortic specimens obtained from participants undergoing open surgical repair.	12 to 36 months

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Collaborators: NHS Lothian; British Heart Foundation
• Investigators: Principal Investigator: Maaz BJ Syed, MBChB MSc, University of Edinburgh

Publications and helpful links

General Publications

• Syed MBJ, Fletcher AJ, Debono S, Forsythe RO, Williams MC, Dweck MR, Shah ASV, Macaskill MG, Tavares A, Denvir MA, Lim K, Wallace WA, Kaczynski J, Clark T, Sellers SL, Masson N, Falah O, Chalmers RTA, Tambyraja AL, van Beek EJR, Newby DE. 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography in Acute Aortic Syndrome. JACC Cardiovasc Imaging. 2022 Jul;15(7):1291-1304. doi: 10.1016/j.jcmg.2022.01.003. Epub 2022 Mar 16.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): February 1, 2021
• Study Completion (ACTUAL): February 1, 2021

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (ACTUAL): August 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 11, 2022
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: positron emission tomography; computed tomography; aortic dissection; sodium fluoride; penetrating aortic ulcer; acute aortic syndrome; intramural haematoma
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease; Hemorrhage; Aneurysm; Syndrome; Aneurysm, Dissecting; Hematoma; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Protective Agents; Cariostatic Agents; Listerine; Fluorides; Sodium Fluoride
• Other Study ID Numbers: AC18044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared outside the current research group

Drug and device information, study documents

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