Clinical trial NCT01186666: Imaging and Biomarkers of Atherosclerosis in Patients With Stable or Unstable Coronary Artery Disease
Official title: BIOmarkers of CORonary Events-2 : Imaging and Biomarkers of Atherosclerosis in Patients With Stable or Unstable Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atherosclerosis
Coronary Artery Disease
Acute Coronary Syndrome
Keywords: Atherosclerosis
Vulnerable plaque
Intravascular ultrasound
Virtual histology
Fluorodeoxyglucose
Positron emission tomography
Multidetector computed tomography
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2010-08-23
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: In this study, multimodal imaging of atherosclerosis and dosage of new circulating biomarkers will be used to compare patients with stable or unstable coronary artery disease

Detailed description: Acute complications of coronary and cerebrovascular atherosclerosis -i.e., acute coronary syndromes (ACS) and strokes - remain the principal cause of death worldwide. Identification of patients at high risk of developing such complications is therefore of utmost importance. Post-MORTEM studies suggest that vulnerable coronary atherosclerotic plaques are characterized by a large, metabolically active, necrotic core, covered by a thin fibrous cap, which may rupture, leading to acute thrombosis, myocardial infarction and, potentially, sudden death. These anatomic features of plaque vulnerability are not visible on standard coronary imaging, such as coronary angiography, but might be recognized using more recent imaging modalities. In addition, new circulating biomarkers of atherosclerosis, particularly biomarkers involved in plaque destabilization, can be measured in peripheral blood and may be used to appreciate overall patient vulnerability.

Design and Methods- In the present study, 2 groups of 44 patients with moderate-to-high risk non-ST elevation ACS or stable coronary artery disease (CAD) will be compared. All the patients will undergo percutaneous coronary intervention of culprit vessels after imaging of the entire coronary tree (culprit and non-culprit lesions) using intravascular ultrasound with radiofrequency data analysis (IVUS-VH). Before discharge, fluorodeoxyglucose positron emission tomography combined with multidetector computed tomography (FDG PET-MDCT) of the carotid arteries and the thoracic aorta, along with MDCT coronary angiography, will be performed and a blood sample will be obtained for subsequent measurements of emerging or new biomarkers.

Objectives -

1. The primary objective is to compare plaque phenotypes between patients with ACS vs stable CAD. For each imaging modality (coronary IVUS-VH, MDCT coronary angiography, AORTO-carotid FDG PET-CT) comparisons will be performed on a per-lesion and per-patient basis.
2. Secondary objectives include: i) An evaluation of the accuracy of each plaque imaging modality and biomarkers for diagnosis of unstable CAD; ii) A comparison of the diagnostic performance of each plaque imaging modality and biomarkers for diagnosis of unstable CAD; iii) A comparison of coronary plaque phenotype between culprit and non-culprit lesions (using IVUS-VH and MDCT coronary angiography); and iv) An exploratory feasibility study of PET-CT imaging of coronary artery atherosclerotic plaques.

It's important to underline that this study must be considered as an interventional study. Indeed, in this study patients have many imaging modality : coronary IVUS-VH, MDCT coronary angiography and AORTO-carotid FDG PET-CT while in common practice patients have only FDG PET-CT which is the routinely technique used.

Eligibility criteria: Inclusion Criteria:

First group: Non ST-elevation acute coronary syndrome

* Symptoms compatible with acute myocardial ischaemia
* Presence of either significant ST-T changes without persistent ST elevation or positive troponin I
* And successful stenting of culprit, de novo coronary stenosis located on native coronary arteries

Second group: Stable coronary artery disease

* Stable angina or silent myocardial ischaemia (documented by a positive stress test)
* And successful stenting of culprit, de novo coronary stenosis located on native coronary arteries

Exclusion Criteria:

In both groups

* Absence of percutaneous coronary angioplasty
* IVUS imaging not feasible
* Heart failure (≥NYHA class 2)
* Severe, persistent arrhythmia
* Renal failure (GFR \< 60 ml/min using MDRD formula)
* History of autoimmune or inflammatory disease, recent sepsis (\< 1 month), neoplasm
* Females without contraception (if at childbearing age)
* Pregnant of child feeding females
* Homeless
* Patients with no health coverage
* Refusal to sing informed consent
* Allergy to FDG or iodinated contrast media

In stable group:

* History of acute coronary syndrome
* History of stroke

Primary outcomes:
measure: Three imaging modalities are used to compare plaque phenotypes between patients with ACS vs stable CAD. (coronary IVUS-VH, MDCT coronary angiography, AORTO-carotid FDG PET-CT)
timeFrame: Performed within 7 days of inclusion
Secondary outcomes:
measure: New circulating biomarkers
timeFrame: Measured on a blood sample performed within 7 days of inclusion
Other outcomes:
Locations:
city: Paris
country: France
facility: Département de Cardiologie, Hôpital Bichat, Assistance Publique - Hôpitaux de Paris
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Laurent Feldman, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Loyau S, Dumont B, Ollivier V, Boulaftali Y, Feldman L, Ajzenberg N, Jandrot-Perrus M. Platelet glycoprotein VI dimerization, an active process inducing receptor competence, is an indicator of platelet reactivity. Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):778-85. doi: 10.1161/ATVBAHA.111.241067. Epub 2011 Dec 8.