Myocardial Infarction
Conditions
Brief summary
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.
Interventions
DRUGDapansutrile
Oral inhibitor of NLRP3
OTHERPlacebo
Non-active placebo
Sponsors
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
Randomized, single blind study.
Eligibility
Sex/Gender
ALL
Age
25 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remote plaque volume | 6 months | Carotid artery plaque volume change by ultrasound measured by 3D ultrasound. Outcome units will be cm3 averaged for bilateral carotid arteries. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plaque inflammation | 3 months | Carotid artery plaque inflammatory activity by PET-CT. Units will be SVU averaged bilaterally for a region-of-interest over the carotid bifurcation. |
| Coronary microvascular function | 3 months | 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). |
Countries
United States
Contacts
Primary ContactJonathan R Lindner, MD
Outcome results
None listed