Advanced Cardiovascular Imaging of the Systemic Effects of Inflammasome Activation

Study Overview
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Brief Summary
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Subjects with urgently reperfused type I myocardial infarction (MI) will be recruited and randomized to receive either placebo or the oral inflammasome (NLRP3) inhibitor dapansutrile. The primarily outcome measure will be carotid plaque volume change over 6 months; secondary outcome measures will be plaque inflammatory activity and coronary microvascular function.

Official Title
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Advanced Cardiovascular Imaging of the Systemic Effects of Inflammasome Activation

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Dapansutrile
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute type I myocardial infarction (NSTEMI or STEMI) Reperfusion therapy planned or performed within prior 48 hrs Carotid or femoral artery plaque at baseline, or carotid intima media thickness >1.5 mm Exclusion Criteria: Type II MI Failed primary PCI or need for emergent bypass surgery Severe heart failure (NYHA class IV) Life-threatening complication of MI (myocardial rupture, ischemic VSD, papillary muscle rupture) Refractory ventricular arrhythmias Allergy to dapansutril, OLT177, or drugs in the same class Co-morbidity limiting 6 month survival Active malignancy or recent malignancy with any systemic anti-cancer treatment Active infection Use of immunosuppressive medications or immunodeficiency disorder Neutropenia (ANC <2,000) Moderate or severe renal impairment (GFR <30 ml/min) Recent stroke (within previous 3 months) Allergy to ultrasound enhancing agents or polyethylene glycol Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, single blind study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapansutrile<br>Subjects randomized to receive oral dapnsutrile | Drug: Dapansutrile<br>* Oral inhibitor of NLRP3<br>|
| Placebo Comparator: Control<br>Subjects randomized to receive oral placebo | Other: Placebo<br>* Non-active placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remote plaque volume | Carotid artery plaque volume change by ultrasound measured by 3D ultrasound. Outcome units will be cm3 averaged for bilateral carotid arteries. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plaque inflammation | Carotid artery plaque inflammatory activity by PET-CT. Units will be SVU averaged bilaterally for a region-of-interest over the carotid bifurcation. | 3 months | 
| Coronary microvascular function | Coronary microvascular reactivity by myocardial contrast echo (MCE) quantitative perfusion imaging. The primary endpoint unit will be coronary microvascular flux rate reserve (regadenoson stress: rest ratio). | 3 months |