Advanced Cardiovascular Imaging of the Systemic Effects of Inflammasome Activation

Early Phase 1

Not yet recruiting

• Conditions: Myocardial Infarction
• Interventions: Other: Placebo; Drug: Dapansutrile

• Registration Number: NCT05880355
• Lead Sponsor: University of Virginia

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-04
• Study First Submitted QC: 2023-05-19
• Study First Posted: 2023-05-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-29
• Last Update Posted: 2023-10-02
• Study Start: 2024-01-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-10-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo	Subjects randomized to receive oral placebo
Dapansutrile	Dapansutrile	Subjects randomized to receive oral dapnsutrile

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States