68Ga-NODAGA-RGD PET in Patients With an Occluded Coronary Artery
- Conditions
- Coronary Artery Disease
- Interventions
- Diagnostic Test: 68Ga-NODAGA-RGD PET-imaging
- Registration Number
- NCT04871217
- Lead Sponsor
- Turku University Hospital
- Brief Summary
Background: In patients with coronary artery disease, acute or chronic coronary artery occlusion is associated with various degrees of ischemic myocardial injury and left ventricle dysfunction. The integrin αVβ3 plays a role in angiogenesis, i.e. formation of new capillaries from pre-existing blood vessels that is increased during repair of ischemic myocardial injury. 68Ga-NODAGA-RGD is a radiopharmaceutical for positron emission tomography (PET) imaging of αVβ3 integrin expression.
Aim: This study aims at evaluating the feasibility of imaging myocardial αVβ3 integrin expression using 68-Ga-NODAGA-RGD PET and whether 68Ga-NODAGA-RGD uptake is associated with myocardial contractile function in patients with an acute or chronic coronary artery occlusion.
Study design: An academic, prospective, open-label study in 60 patients with an acute or chronic coronary occlusion.
Study population: 30 patients with an ST-elevation acute myocardial infarction weeks and left ventricular ejection fraction \<50%. 30 patients with planned percutaneous re-opening of a chronic coronary total occlusion and left ventricular ejection fraction \<50%.
Study procedures: Patients will undergo cardiac 68Ga-NODAGA-RGD PET within 3 to 14 days after an ST-elevation acute myocardial infarction or within 4 weeks before and 2 weeks after planned percutaneous re-opening of chronic coronary total occlusion. Myocardial perfusion reserve will be evaluated in patients with chronic total occlusion by PET. Echocardiography will be performed at the time of PET imaging and repeated 6 months later to evaluate global and regional left ventricle contractile function. Data on relevant cardiovascular clinical history and blood sample will be obtained at imaging visits. Cardiac events will be evaluated after two years.
End-points: Primary: Myocardial uptake of 68-Ga-NODAGA-RGD after an acute myocardial infarction or before and after opening of chronic coronary occlusion. Secondary: Global and regional left ventricle systolic function. Blood biomarkers of myocardial injury and heart failure. Myocardial perfusion reserve. Adverse cardiac events including death, myocardial infarction, unstable angina pectoris, repeat revascularization and heart failure hospitalizations.
- Detailed Description
Background: In patients with coronary artery disease, acute or chronic coronary artery occlusion is associated with various degrees of ischemic myocardial injury and left ventricle dysfunction. The integrin αVβ3 plays a role in angiogenesis (Brooks 1994), i.e. formation of new capillaries from pre-existing blood vessels that is increased during repair of ischemic myocardial injury (Meoli 2004, Higuchi 2008, Sherif 2012, Sun 2003, Jenkins 2017). 68Ga-NODAGA-RGD is a radiopharmaceutical for positron emission tomography (PET) imaging of αVβ3 integrin expression (Grönman 2017, Buchegger 2011, Pohle 2012, Gnesin 2017).
Aim: This study aims at evaluating the feasibility of imaging myocardial αVβ3 integrin expression using 68-Ga-NODAGA-RGD PET and whether 68Ga-NODAGA-RGD uptake is associated with myocardial contractile function in patients with an acute or chronic coronary artery occlusion.
Study design: An investigator-initiated, prospective, open-label study in 60 patients with an acute or chronic coronary occlusion.
Study population: 30 patients with an ST-elevation acute myocardial infarction weeks and left ventricular ejection fraction \<50%. 30 patients with planned percutaneous re-opening of a chronic coronary total occlusion and left ventricular ejection fraction \<50%.
Study procedures: Patients will undergo cardiac 68Ga-NODAGA-RGD PET within 3 to 14 days after an ST-elevation acute myocardial infarction or within 4 weeks before and 2 weeks after planned percutaneous re-opening of chronic coronary total occlusion. Myocardial perfusion reserve will be evaluated in patients with chronic total occlusion by PET myocardial perfusion imaging. Complete echocardiography will be performed at the time of PET imaging and repeated 6 months later to evaluate global and regional left ventricle contractile function. Data on relevant cardiovascular clinical history and blood sample will be obtained at imaging visits. Cardiac events will be evaluated after two years.
Primary end-point: Myocardial uptake of 68-Ga-NODAGA-RGD after an acute myocardial infarction or before and after opening of chronic coronary occlusion. Secondary end-points: Global and regional left ventricle systolic function. Blood biomarkers of myocardial injury (troponin) and heart failure (pro-BNP). Myocardial perfusion reserve. Adverse cardiac events including death, myocardial infarction, unstable angina pectoris, repeat revascularization and heart failure hospitalizations.
Sample size: This is an exploratory study and formal power calculation cannot be performed.
Ethical aspects: The study conforms to the World Medical Association Declaration of Helsinki. Written statement will be obtained from the ethics committee (the Ethical Board of the South-Western Finland). Permissions from regulatory authorities (the Finnish Medicines Agency Fimea) and the Turku University Hospital for conducting the study will be obtained. Signed and dated informed consent will be obtained from patients before conducting any study specific procedures.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
- ST-elevation acute myocardial infarction within 3-14 days
- Planned elective percutaneous revascularization of angiographically documented coronary chronic total occlusion (CTO)
- Left ventricular ejection fraction < 50% when hospitalized for index acute myocardial infarction or within 12 months before planned revascularization of coronary CTO
- Provision of signed and dated informed consent prior to study specific procedures
- Current unstable angina
- Significant valvular heart disease
- NYHA IV heart failure symptoms
- Severe untreated hypertension (>180/110 mmHg)
- Female not post-menopausal
- Contraindications for adenosine infusion (in patients with CTO):
- Severe renal failure (estimated glomerular filtration rate < 30 ml/min)
- Atrial fibrillation with ventricular response > 110 bpm
- No acoustic window for left ventricle assessment by echocardiography
- Previous cardiac surgery
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Acute ST-elevation myocardial infarction or chronic coronary artery occlusion 68Ga-NODAGA-RGD PET-imaging 68-Ga-NODAGA-RGD PET after acute ST-elevation myocardial infarction or before and after re-opening of a chronic coronary artery occlusion
- Primary Outcome Measures
Name Time Method Myocardial uptake of 68Ga-NODAGA-RGD after acute myocardial infarction 3 to 14 days after acute myocardial infarction 68Ga-NODAGA-RGD uptake in PET images in the myocardial territory supplied by the occluded coronary artery vs. remote myocardium after an acute myocardial infarction
Myocardial uptake of 68Ga-NODAGA-RGD before and after opening of chronic coronary occlusion Within 4 weeks before and 2 weeks after re-opening of a chronic coronary occlusion Change in 68Ga-NODAGA-RGD uptake in PET images in the myocardial territory supplied by the occluded coronary artery before and after opening of a chronic coronary occlusion
- Secondary Outcome Measures
Name Time Method Regional left ventricle systolic function At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up Regional myocardial strain (%) assessed by echocardiography
Global left ventricle systolic function At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up Left ventricle ejection fraction (%) assessed by echocardiography
Adverse cardiac events After 2 years of follow-up Number of patients with myocardial infarction, unstable angina pectoris, repeat revascularization, heart failure hospitalization or death
Blood biomarker of heart failure At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up pro-BNP (ng/L)
Blood biomarker of myocardial injury At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up Cardiac troponin T (ng/L)
Myocardial perfusion reserve At the time of 68Ga-NODAGA-RGD PET imaging within 4 weeks before and 2 weeks after re-opening of a chronic coronary occlusion Assessed by PET myocardial perfusion imaging before and after re-opening of chronic coronary occlusion
Trial Locations
- Locations (3)
Turku University Hospital
🇫🇮Turku, Finland
University of Lausanne Hospitals
🇨🇭Lausanne, Switzerland
Leiden Medical Center
🇳🇱Leiden, Netherlands