The Heartflow Coronary Disease Progression Evaluation Study (THRONE)

Invasively measured fractional flow reserve (FFR) has proven to be useful in guiding coronary revascularization. Several studies have shown that it is justified to treat lesions with a value of 0.80 or lower and safe to defer from PCI in lesions with a value of >0.80. Recently, computational fluid dynamics have allowed FFR measurement from coronary computed tomography angiography images (FFRCT) with excellent diagnostic accuracy compared to invasive FFR.

FFRCT can also effectively guide revascularization safely deferring patient with FFRCT >0.80 from invasive angiography. In functionally non-significant lesions, computational fluid dynamic models in addition to CT plaque characteristics (low attenuation, positive remodelling, spotty calcification and napkin-ring sign) may be able to predict which lesions will become flow-limiting, causing clinical events in the future.

This study will evaluate disease progression in intermediate lesions (invasive FFR 0.81-0.90 at baseline) using FFRCT at 2 years and determine whether CT characteristics may help to identify lesions that are more susceptible for FFR decline. Additionally, we will correlate CT characteristics with coronary events (a composite endpoint consisting of all-cause mortality, target-vessel myocardial infarction and clinically driven target-vessel revascularization) up to 5 years after the baseline invasive FFR.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: Coronary computed tomography angiography

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

• Study Contact: Name: Nicolas van Mieghem, MD, PhD; Phone Number: 00311070438894; Email: n.vanmieghem@erasmusmc.nl
• Study Contact Backup: Name: Admir Dedic, MD, PhD; Phone Number: 00311070438894; Email: a.dedic@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
    • Contact: Admir Dedic, MD, PhD; Phone Number: 00311070438894; Email: a.dedic@erasmusmc.nl
    • Sub-Investigator: Admir Dedic, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients (age ≥ 18 years) treated with PCI (for non-ST elevation myocardial infarction, unstable or stable angina and silent ischemia) or who undergo invasive FFR.

Description

Inclusion Criteria:

1. Patients (age ≥ 18 years) treated with PCI (for non-ST elevation myocardial infarction, unstable or stable angina and silent ischemia) or who undergo invasive FFR.
2. Minimum of one non-treated coronary artery with an intermediate lesion and invasive FFR 0.81-0.90 to serve as the target vessel for FFRCT.

Exclusion Criteria:

1. ST elevation myocardial infarction.
2. Previous CABG.
3. Target vessel for FFR measurement < 2.0 mm in diameter.
4. Contraindications to contrast agents, beta-blocking agents, nitroglycerin or adenosine.
5. Life expectancy less than 3 years.
6. Creatinine clearance < 30 ml/min*1.73m2.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with intermediate coronary lesions; Patients (age ≥ 18 years) who have undergone invasive coronary angiography and have a minimum of one non-treated coronary artery with a measured invasive FFR of 0.81-0.90.	Diagnostic test: Coronary computed tomography angiography; Computational fluid dynamic model information derived from CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary atherosclerotic disease progression	FFRCT	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion failure Target vessel failure	Composite of all-cause mortality, target-vessel myocardial infarction and cinically driven target vessel revascularization.	3-5 years
Any coronary revascularisation		3-5 years

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Study Chair: Jonathan A Leipsic, MD, PhD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 5, 2018
• Primary Completion (ANTICIPATED): October 1, 2022
• Study Completion (ANTICIPATED): October 1, 2023

Study Registration Dates

• First Submitted: August 8, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (ACTUAL): August 9, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Fractional flow reserve; Computational fluid dynamics; Coronary computed tomography angiography; Plaque characteristics
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Coronary Artery Disease; Coronary Disease; Disease Progression
• Other Study ID Numbers: THRONE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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