## Protocol Section
### Identification Module
**NCT ID:** NCT06438393

**Acronym:** SAFE-CT

**Brief Title:** Screening Coronary Artery Disease Using artiFicial intelligencE in Non-contrast Computed Tomography

**Official Title:** Screening Coronary Artery Disease Using artiFicial intelligencE in Non-contrast Computed Tomography

#### Organization Study ID Info
**ID:** SAFE-CT
#### Organization
**Class:** OTHER
**Full Name:** Universidade do Porto
### Status Module
#### Completion Date
**Date:** 2027-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-27

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-02

#### Study First Post Date
**Date:** 2024-05-31
**Type:** ESTIMATED
**Study First Submit Date:** 2024-05-27
**Study First Submit QC Date:** 2024-05-27
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** University of Oxford

**Class:** OTHER

**Name:** University of Edinburgh

#### Lead Sponsor

**Class:** OTHER

**Name:** Universidade do Porto

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This project aims to improve direct patient care by reducing the risks of futile exposure to ionizing radiation and iodinated contrast in patients referred for coronary computed tomography angiography

**Detailed Description:** Since the last NICE guidelines update recommending computed tomography coronary angiography (CTCA) as the first line of investigation for patients with suspected coronary artery disease (CAD), there has been a high burden in the healthcare system and unnecessary exposition to radiation and iodine-containing contrast medium, especially in the youngest. Around 35% of patients who currently undergo CTCA have normal coronaries which means those patients were unnecessary exposed to radiation and contrast. A CTCA screening strategy to rule out CAD is needed to comply with the ALARA ("As Low As Reasonable Achievable") principles preventing radiation risks, reducing unnecessary scans and directing healthcare resources to those who will benefit from a CTCA.

We designed the SAFE-CT (Screening coronary Artery disease using artiFicial intelligencE in noncontrast Computed Tomography) study to develop a state-of-art artificial intelligence method to detect CAD as defined on CTCA using high-dimensional data (radiomics) extracted from the non-contrast cardiac computed tomography (CT). The model will be trained in 15,000 subjects scanned with paired non-contrast CT and CTCA and externally validated in an independent cohort of 1,000 subjects. In a preliminary analysis, non-contrast CT radiomics improved calcium score performance and discriminated CAD with an AUC of 0.91 (95% CI: 0.83-1.00). The algorithm will be converted into a user-friendly plugin to automatically decide whether the patient needs contrast. A real-world multicentre cohort study will be planned for software prospective validation and the creation of a large-scale proteomic biobank to support the translation of imaging biomarkers worldwide.

SAFE-CT can change the current CT scanning workflow by creating software that accurately rules out any CAD in \>1/3 of patients referred for CTCA with low radiation and no contrast. This accurate machine learning model will be optimized to reach \>90% sensitivity and negative predictive value and will bring several advantages for patients and the healthcare system:

* Prevention of radiation and contrast exposition.
* Increased CTCA scanning capacity for complex cases.
* Widespread use of CT for CAD exclusion in the emergency department and in outpatient clinics of centres with no CTCA.
* Improved screening tool for CAD in asymptomatic subjects.
* Up- and downstream cost reduction.

The SAFE-CT project proposes a safer, low-cost, and personalized CTCA scanning strategy that fosters scientific and technological innovation with the potential to bring improvement to patient care and clinical practice, and, thereby, societal, and economic impact.

### Conditions Module

**Conditions:**

- Coronary Artery Disease

- Coronary Atheroscleroses

**Keywords:**

- Artificial intelligence

- Radiomics

- Deep learning

- Coronary artery disease

- Non-contrast computed tomography

### Design Module

#### Bio Spec

**Description:** Peripheral blood samples for proteomics analysis

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** OTHER

**Time Perspective:** RETROSPECTIVE

#### Enrollment Info

**Count:** 1000

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** CAD: Presence of minimal coronary artery disease (i.e., coronary stenosis 0-25%) Normal coronary arteries: No visible coronary atherosclerosis

**Intervention Names:**

- Diagnostic Test: CT coronary angiography and non-contrast CT

**Label:** Stable chest pain and unknown CAD who underwent CTCA and CCS in the same scanning session

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Stable chest pain and unknown CAD who underwent CTCA and CCS in the same scanning session

**Description:** A CTCA is an X-ray computed tomography of the coronary arteries that allows visualization of coronary plaques with high temporal and spatial resolution, however, it implies the use of iodine contrast and exposition to clinically significant ionizing radiation.

Non-contrast ECG-gated CT ("calcium score" - CCS image). A non-contrast cardiac CT for CCS can be performed very quickly with significantly lower radiation (\~6 times lower) than CTCA and without the need for contrast.

**Name:** CT coronary angiography and non-contrast CT

**Other Names:**

- Non-contrast computed tomography

**Type:** DIAGNOSTIC_TEST

### Outcomes Module

#### Primary Outcomes

**Measure:** Build a non-contrast CT radiomic signature of CAD

**Time Frame:** 3 years

**Measure:** Implement a machine learning model to discriminate patients with no CAD from patients with at least minimal disease (CAD-RADS=0 vs. CAD-RADS>0).

**Time Frame:** 3 years

**Measure:** Implement a machine learning model to detect coronary inflammation as defined using the Fat Attenuation Index (FAI ≥ -70.1 HU) in patients with no visible coronary plaque (CAD-RADS=0).

**Time Frame:** 3 years

**Measure:** Build a user-friendly plugin to facilitate users experience and distribution of our technology in clinical practice.

**Time Frame:** 3 years

**Measure:** Evaluate the real-world operationality and performance of the plugin in an international multicentre prospective cohort study.

**Time Frame:** 3 years

**Measure:** Create a national registry of cardiac CT

**Time Frame:** 3 years

#### Secondary Outcomes

**Measure:** Setup a human blood biobank to identify the peripheral blood mononuclear cells (PBMCs) and plasma proteomics associated with CT data and clinical outcomes.

**Time Frame:** 3 years

**Measure:** Setup a public CT imaging repository

**Time Frame:** 3 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

- Patient with stable chest pain who underwent a CTCA

Exclusion Criteria:

* Missing non-contrast CT image (coronary calcium score image)
* Known coronary artery disease
* Prior myocardial infarction
* Prior PCI or CABG

**Healthy Volunteers:** True

**Maximum Age:** 100 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Stable chest pain patients with unknown CAD who underwent a CTCA with paired non-contrast CT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Porto

**Country:** Portugal

**Facility:** Faculty of Medicine of Porto

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000001161

- Term: Arteriosclerosis

- ID: D000001157

- Term: Arterial Occlusive Diseases

- ID: D000014652

- Term: Vascular Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M6546

- Name: Coronary Artery Disease

- Relevance: HIGH

- As Found: Coronary Artery Disease

- ID: M19506

- Name: Myocardial Ischemia

- Relevance: HIGH

- As Found: Coronary Artery Disease

- ID: M6549

- Name: Coronary Disease

- Relevance: HIGH

- As Found: Coronary Artery Disease

- ID: M26188

- Name: Atherosclerosis

- Relevance: HIGH

- As Found: Atherosclerosis

- ID: M10543

- Name: Ischemia

- Relevance: LOW

- As Found: Unknown

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4469

- Name: Arteriosclerosis

- Relevance: LOW

- As Found: Unknown

- ID: M4465

- Name: Arterial Occlusive Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003324

- Term: Coronary Artery Disease

- ID: D000017202

- Term: Myocardial Ischemia

- ID: D000003327

- Term: Coronary Disease

- ID: D000050197

- Term: Atherosclerosis

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M5381

- Name: Calcium

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: LOW

- As Found: Unknown

- ID: M10488

- Name: Iodine

- Relevance: LOW

- As Found: Unknown

- ID: M229695

- Name: Cadexomer iodine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
