Synergy Between morpHOlogical and inflammatoRy Evaluation in Predicting Long-term Coronary Plaque Progression (SHORE)

Data from human autopsy studies have showed that thrombosis of a ruptured plaque with a large necrotic core, inflammatory cells and a thin fibrous cap, the so-called thin cap fibroatheroma (TCFA), represents the main mechanism for acute coronary syndrome (ACS). Optical coherence tomography (OCT) is an imaging technique that provides high-resolution, cross-sectional images of tissue in situ. The resolution of OCT (10 um) is appropriate for measuring a cap thickness less than65 μm, and even the plaque macrophage density. 68Ga-DOTA-(Tyr3)-octreotate/NaI3-octreotide(68Ga-DOTA-TATE/NOC) Positron Emission Tomography (PET)/Computed Tomography coronary angiography (CTCA), targeting the somatostatin receptor subtype-2 selectively expressed by M1 macrophages may show coronary inflammation. The SHORE protocol aims at evaluating the synergy between OCT and 68Ga-DOTA-TATE/NOC in predicting coronary plaque progression as assessed by CTCA

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Inflammation; Atherosclerosis; Acute Coronary Syndrome
• Intervention / Treatment: Diagnostic test: coronary OCT; Diagnostic test: 68GaDOTATATE PET/CTCA

Detailed Description

ACS are the leading cause of mortality and morbidity in the western world. Despite recommended therapies, after experiencing an ACS episode patients still have an increased cardiovascular risk during follow up. In the CLIMA study OCT criteria of plaque vulnerability at non-culprit sites such as minimum luminal area <3.5mm2, fibrous cap thickness <75 µm, lipid arc extension >180° and macrophage infiltration was associated with an increased risk of cardiac death and myocardial infarction (HR 7.54, 95%CI 3.1-18.6).

Of the 36 OCT defined vulnerable plaques only 7 were associated with events showing a very low positive predictive value (19%). Yet, among the 577 plaques with macrophages accumulation only the 5.2% was associated with the endpoint. The lack of reliable information on plaque inflammation could represent the miss point to better link high risk plaques to plaque progression and/or rupture. Recent studies showed that inflammation in coronary plaques may be measured by means 68Ga-DOTATATE/PET targeting the somatostatin receptor subtype-2 selectively expressed by M1 macrophages.

Thus the investigators aim to evaluate the in vivo natural history of coronary plaques characterized from both the morphological (OCT) and inflammatory (68Ga-DOTATATE PET/CTCA) point of view in patients with ACS and at least 1 intermediated coronary lesion as assessed by FFR/iFR

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nevio Taglieri, MD; Phone Number: +390512144475; Email: nevio.taglieri@unibo.it

Study Locations

• Italy
  • Bologna, Italy
    • Recruiting
    • University of Bologna IRCCS Policlinico di St. Orsola
    • Contact: Nevio Taglieri, MD
    • Principal Investigator: Nevio Taglieri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female participants > 50 years old
• Able to give written, informed consent and to lie flat
• Presentation of ACS within ~2 weeks
• At least 1 intermediate (30-80% diameter stenosis) non-culprit coronary artery lesion on angiography, managed medically as clinically indicated (i.e.: negative FFR/iFR)

Exclusion Criteria:

• Women of child bearing potential not using adequate contraception
• Contrast allergy or contrast-nephropathy
• Uncontrolled atrial fibrillation
• Chronic kidney disease (eGFR <30 l/min/1.73m2)
• Uncontrolled chronic inflammatory disorder
• History of recent malignancy deemed relevant to the study by the investigator
• Current use of systemic corticosteroids
• Previous coronary artery bypass grafting surgery (CABG) or percutaneous coronary intervention (PCI) before the index event
• Contraindication to coronary angiography
• Requires CABG or staged non-culprit artery PCI
• Coronary vessels that could not be adequately imaged
• Severe valvular heart disease
• Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Plaque Progression	Comparison of baseline non culprit OCT imaging and baseline 68Ga-DOTANOC tissue-to-blood ratio in patients with significant plaque progression measured by CTCA (defined by changes in low attenuation plaque volume and total atheroma volume), versus those without	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Plaque Progression	Comparison of baseline non culprit OCT imaging and 12 weeks 68Ga-DOTANOC tissue-to-blood ratio in patients with significant plaque progression measured at 2 years follow up by CTCA (defined by change in low attenuation plaque volume and total atheroma volume), versus those without	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between OCT and PET findings	Comparison of 68Ga-DOTANOC imaging to OCT assessed plaque morphology	baseline

Collaborators and Investigators

• Sponsor: University of Bologna
• Collaborators: University of Cambridge; Centro per la Lotta Contro l'Infarto - Fondazione Onlus

Publications and helpful links

General Publications

• Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Ozaki Y, Marco V, Boi A, Fineschi M, Fabbiocchi F, Taglieri N, Niccoli G, Trani C, Versaci F, Calligaris G, Ruscica G, Di Giorgio A, Vergallo R, Albertucci M, Biondi-Zoccai G, Tamburino C, Crea F, Alfonso F, Arbustini E. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study. Eur Heart J. 2020 Jan 14;41(3):383-391. doi: 10.1093/eurheartj/ehz520. Erratum In: Eur Heart J. 2020 Jan 14;41(3):393.
• Tarkin JM, Joshi FR, Evans NR, Chowdhury MM, Figg NL, Shah AV, Starks LT, Martin-Garrido A, Manavaki R, Yu E, Kuc RE, Grassi L, Kreuzhuber R, Kostadima MA, Frontini M, Kirkpatrick PJ, Coughlin PA, Gopalan D, Fryer TD, Buscombe JR, Groves AM, Ouwehand WH, Bennett MR, Warburton EA, Davenport AP, Rudd JH. Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging. J Am Coll Cardiol. 2017 Apr 11;69(14):1774-1791. doi: 10.1016/j.jacc.2017.01.060.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 21, 2021
• Primary Completion (ANTICIPATED): June 21, 2024
• Study Completion (ANTICIPATED): June 21, 2024

Study Registration Dates

• First Submitted: June 1, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (ACTUAL): June 29, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 29, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Inflammation; Atherosclerosis; Acute Coronary Syndrome
• Other Study ID Numbers: SHORE_Bo_2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This protocol has been designed in collaboration with researchers in the United Kingdom, with the intention of combining data from the SHORE study with the Residual Inflammation and Plaque Progression Long-term Evaluation (RIPPLE; NCT04073810) study that is jointly sponsored by the University of Cambridge and Cambridge University Hospitals NHS Trust, UK.
• IPD Sharing Time Frame: Data will be available after the recruiting phase and till the end of the study
• IPD Sharing Access Criteria: Only investigators of the Ripple study will have access to the data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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