PROTEUS: Evaluating the Use of Artificial Intelligence to Support Stress Echocardiography Testing for Heart Disease (PROTEUS)

PROTEUS: A PROspective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiology

PROTEUS is a multicentre, two arm, randomised controlled trial of a medical device to assess the impact of the introduction of EchoGo into the standard care pathway for stress echocardiology.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Diagnostic test: EchoGo

Detailed Description

Title: A Prospective Randomised Controlled Trial Evaluating the Use of AI in Stress Echocardiography

Trial design: Multi-centre, two-arm, Randomised Controlled Trial of a medical device. Randomised 1:1 to either:

• Standard care (comparator), or
• Standard care plus AI Platform (EchoGo) Trial participants: Adults undergoing clinically indicated stress echocardiogram (SE) to assess inducible ischaemia at participating NHS Trusts.

Having benchmarked the device performance (Upton 2019), and having successfully deployed and tested the required infrastructure, we now propose to prospectively test the software in clinical practice. Based on the existing data for accuracy we would expect use of the EchoGo Platform in the clinical pathway will have a significant benefit reducing inter-reader variability, increasing accuracy and thereby reducing health costs. To formally evaluate the impact of automated AI quantification and accuracy of the decision to make a referral to coronary angiogram, following stress echocardiography, we propose a prospective, multi-centre, randomised controlled trial that compares provision of an AI derived report to a clinician against clinician-only standard of care. This will provide the highest level of evidence of any potential benefit or disadvantages prior to adoption of the software for widespread clinical implementation.

• Study Type: Interventional
• Enrollment (Actual): 2338
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Basildon, United Kingdom
    • Mid and South Essex NHS Foundation Trust
  • Bath, United Kingdom
    • Royal United Hospitals Bath
  • Birmingham, United Kingdom
    • University Hospitals Birmingham NHS Foundation Trust
  • Blackpool, United Kingdom
    • Blackpool Victoria Hospital
  • Coventry, United Kingdom
    • University Hospitals Coventry & Warwickshire
  • Hexham, United Kingdom
    • Northumbria Healthcare NHS Foundation Trust
  • High Wycombe, United Kingdom
    • Buckinghamshire Healthcare NHS Trust
  • Ipswich, United Kingdom
    • Ipswich General Hospital
  • Leicester, United Kingdom
    • Leicester General Hospital
  • London, United Kingdom
    • St George's University Hospitals NHS Foundation Trust
  • Milton Keynes, United Kingdom
    • Milton Keynes University Hospital
  • Northampton, United Kingdom
    • Northampton General Hospital NHS Trust
  • Oldham, United Kingdom
    • Royal Oldham Hospital
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Foundation Trust
  • Peterborough, United Kingdom
    • North West Anglia NHS Foundation Trust
  • Reading, United Kingdom
    • Royal Berkshire Hospital
  • Salford, United Kingdom
    • Salford Royal Hospital
  • Stockport, United Kingdom
    • Stockport NHS Foundation Trust
  • Wigan, United Kingdom
    • Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust
  • Oxfordshire
    • Swindon, Oxfordshire, United Kingdom
      • Great Western Hospitals NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and able to provide informed consent
• Male or female, ≥18 years of age at study entry
• Referred to an NHS Trust for stress echocardiography for investigation of ischaemic heart disease

Exclusion Criteria:

• More than moderate valvular heart disease
• Left ventricular outflow tract obstruction defined as a gradient > 30mmHg (fixed or dynamic; supravalvular, valvular or sub-valvular)
• Significant co-morbidities (e.g. cancer) with an expected life-expectancy of under 12 months in the investigator's opinion
• Previous coronary artery bypass graft or other cardiac surgery
• Congenital or inherited myocardial disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Care (comparator); Patients will receive standard care
Experimental: Standard Care plus AI platform (EchoGo); Patients will receive standard care plus their Echocardiogram will be sent to Ultromics for AI assessment. The report from the assessment will be sent to the clinician, and utilised to inform the patients further care.	Diagnostic test: EchoGo; EchoGo Pro is an software Medical Device which is able to assess Stress Echocardiograms and provide a binary classification of risk of CAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate if EchoGo plus standard care is non-inferior to standard care alone for aiding referral to coronary angiogram following stress echocardiogram (SE)	Outcome measure - AUROC for the ability to make an appropriate referral to coronary angiogram at 6 months following stress echocardiogram. Appropriate management will be defined as a composite of; coronary angiography that demonstrates severe coronary disease fulfilling clinical care guidelines for revascularisation or; decision for medical management/reassurance without unanticipated serious adverse cardiac events Outcome data will be collected from participant's medical records at 3 and 6 months.	6 months post stress echo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish if clinical management decision making is affected by review of the EchoGo report.	Establish if clinical management decision making is affected by review of the EchoGo report as recorded by clinician self-report.	6 month
Establish if using the EchoGo platform affects clinician diagnostic confidence.	Clinician diagnostic confidence in their interpretation of the stress echo report will be measured by clinician self-report at baseline, 3 months and end of study at each participating site.	3 and 6 months post stress echo
Establish if clinician diagnostic performance variance reduces with EchoGo use.	Outcome measured by Inter-clinician and in-site variability at baseline, 3 months and at end of study.	3 and 6 month post stress echo
Establish if using Ultromics' EchoGo Platform affects the number of subsequent investigations for cardiovascular disease. for cardiovascular disease	Outcome shall be measured through collation of the number of incidences of the following (occurring up to 6 months following stress echo): Myocardial Perfusion Scan; CT coronary angiogram; Stress echo; Invasive coronary angiogram; Stress CMR; Exercise tolerance test; Initiation of anti-anginal medication/medical management of angina Data will be collected from participants medical records at 3 and 6 months	3 and 6 months post stress echo
Establish if using Ultromics' EchoGo Platform affects patient reported coronary artery disease symptoms.	Outcome shall be measured through the collation of the number of coronary artery disease symptoms and impact on participant health status as measured by patient-reported short Seattle Angina Questionnaire (SAQ-7) at trial entry, 3 months and 6 months	3 and 6 months post stress echo
Investigate if EchoGo plus standard care is superior to standard care alone in predicting the risk of severe cardiovascular disease following stress echocardiogram (SE)	Outcome shall be measured through - AUROC for the ability to make an appropriate referral to coronary angiogram.	6 month post stress echo
Investigate the appropriate clinical management decisions made when using EchoGo plus standard care compared to standard care alone.	Outcome measure - Appropriate clinical management following an echocardiogram, for referring a patient to coronary angiogram, determined by adjudication committee review of follow up data.	6 month post stress echo
Assess the health economics impact of implementation and use of Ultromics' EchoGo platform in NHS units	Outcome measure - Patient reported health related quality of life	3 and 6 month post stress echo

Collaborators and Investigators

• Sponsor: Ultromics Ltd
• Collaborators: University of Oxford; National Institute for Health Research, United Kingdom; Academic Health Science Centres

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Actual): June 30, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: COL-69

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No