Residual Inflammation and Plaque Progression Long-term Evaluation

Active, not recruiting

• Conditions: Atherosclerosis; Myocardial Infarction; Coronary Artery Disease; Inflammation
• Interventions: Diagnostic Test: PET imaging; Diagnostic Test: Coronary CT angiography; Diagnostic Test: Cardiac MRI

• Registration Number: NCT04073810
• Lead Sponsor: University of Cambridge

Brief Summary

Inflammation drives atherosclerotic plaque rupture triggering most acute coronary syndromes. Despite advances in diagnosis and management of atherosclerosis, patients with myocardial infarction (MI) remain at increased risk of recurrent events. The RIPPLE study aims to examine the relationship between residual coronary inflammation detected by 68Ga-DOTATATE PET in patients treated for MI to long-term plaque progression measured by CT coronary angiography (CTCA). The association between infarct-related myocardial 68Ga-DOTATATE PET and myocardial function and viability will also be assessed.

Detailed Description

While vascular inflammation can be detected using 18F-FDG PET, this method lacks inflammatory cell specificity and is unreliable for coronary imaging because of high background signals from the myocardium. Upregulation of somatostatin receptor subtype-2 (SST2) occurs in activated macrophages, offering a novel inflammation imaging target. 68Ga-DOTATATE, an SST2 PET tracer with low myocardial binding, shows promise for imaging coronary inflammation. Having previously demonstrated increased 68Ga-DOTATATE signals in coronary atherosclerotic lesions post-MI, we now aim to study the natural history of residual arterial inflammation in non-culprit arteries and better understand how 68Ga-DOTATATE signals relate to plaque morphology, progression and rupture. Residual infarct-related myocardial inflammation and its association with ischemic myocardial remodelling will also be examined.

Study Timeline

• Study First Submitted: 2019-08-27
• Study First Submitted QC: 2019-08-27
• Study First Posted: 2019-08-29
• Study Start: 2020-10-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-18
• Last Update Posted: 2024-07-19
• Primary Completion: 2024-12-01
• Study Completion: 2025-04-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Male or female participants >18 years old
• Able to give written, informed consent and to lie flat
• First-presentation of myocardial infarction within ~2 weeks
• At least mild non-culprit coronary artery disease on angiography, managed medically

Exclusion Criteria

• Women of child bearing potential not using adequate contraception
• Contrast allergy or contrast-nephropathy
• Uncontrolled atrial fibrillation
• Chronic kidney disease (eGFR <30 mL/min/1.73 m2)
• Any medical condition, in the opinion of the investigator, that prevents the participant from lying flat during scanning, or from participating in the study
• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Myocardial infarction	Cardiac MRI	Patients with recent MI
Myocardial infarction	PET imaging	Patients with recent MI
Myocardial infarction	Coronary CT angiography	Patients with recent MI

Primary Outcome Measures

Name	Time	Method
68Ga-DOTATATE PET vs. plaque progression	2 years	Comparison of non-culprit coronary artery 68Ga-DOTATATE tissue-to-blood ratio at 12 weeks post-MI in patients with plaque progression (changes in low attenuation plaque volume and total atheroma volume) after 2 years measured by CTCA versus those without

Secondary Outcome Measures

Name	Time	Method
68Ga-DOTATATE PET vs. CTCA-defined plaque morphology	2 years	Comparison of coronary 68Ga-DOTATATE imaging to changes in plaque morphology measured by CTCA
68Ga-DOTATATE PET vs. intravascular imaging	Baseline	Comparison of 68Ga-DOTATATE imaging to plaque morphology defined by high-resolution intravascular imaging performed during invasive coronary angiography
68Ga-DOTATATE PET vs. hsCRP	2 years	Comparison of 68Ga-DOTATATE PET to high-sensitivity C-reactive protein
68Ga-DOTATATE PET vs left ventricular myocardial function	1 year	Comparison of myocardial 68Ga-DOTATATE PET to left ventricular size and function
68Ga-DOTATATE PET vs myocardial tissue characterization	1 year	Comparison of myocardial 68Ga-DOTATATE PET to myocardial scarring and oedema

Trial Locations

Locations (1)

University of Cambridge; 🇬🇧 Cambridge, United Kingdom