The primary goal of this clinical trial is to test the hypothesis that the drug canakinumab (anti-IL-1B monoclonal antibody) decreases vascular inflammation when used by people with a history of coronary artery disease, including those with and without clonal hematopoiesis driven by mutations in TET2.
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Eligibility Criteria
Inclusion Criteria:
* 18 years or older
* Coronary artery disease, defined as prior heart attack, coronary stent procedure \>180 days before baseline imaging, or advanced subclinical coronary atherosclerosis (coronary artery calcium score ≥300 Agatston units, CAD-RADS 3 or greater atherosclerosis o…
Inclusion Criteria:
* 18 years or older
* Coronary artery disease, defined as prior heart attack, coronary stent procedure \>180 days before baseline imaging, or advanced subclinical coronary atherosclerosis (coronary artery calcium score ≥300 Agatston units, CAD-RADS 3 or greater atherosclerosis on coronary CT angiography, or qualitatively severe coronary artery calcification identified on non-gated CT imaging)
* Presence of either TET2 mutations or no myeloid driver mutations on prior sequencing
Exclusion Criteria:
* placement of a drug-eluting stent in a proximal coronary arterial segment \<180 days before baseline imaging
* prior coronary artery bypass grafting
* pregnancy or breastfeeding
* history of blood malignancy or current solid-tumor malignancy
* history of organ or stem cell transplantation
* current treatment with prescription, systemic (oral, IV \[intravenous\], or IM \[intramuscular\]) steroids or anti-inflammatory/immune suppressant medical therapies (including colchicine but excluding topical therapies, UV therapy, ASA-derivative therapies, or NSAIDS) for autoimmune/inflammatory diseases, post-transplant care, asthma, or pain
* use of oral steroids or prescription oral anti-inflammatory/immune suppressant medication for \>7 days within the past 1 month
* use of IV or IM steroids or IV or IM anti-inflammatory/immune suppressant medication within the past 3 months
* known allergy to dextran's and/or DTPA and/or radiometals and/or severe allergy to iodinated contrast media
* estimated glomerular filtration rate (eGFR) \< 45 ml/min/1.73 m2
* contraindications to nitroglycerin known narrow angle glaucoma, or known severe aortic stenosis
* use of phosphodiesterase type 5 inhibitor AND refusal to abstain from use of these medications within the 5 days prior to scheduled CCTA scan
* significant radiation exposure (40msV) received within the past 12 months
* concurrent enrollment in another research study judged by the investigators to interfere with the current study
* known active or recurrent hepatic disease (including cirrhosis or ALT/AST levels \>3 times the upper limit oof or total bilirubin \>2 times the upper limits of normal)
* history or evidence of tuberculosis (TB) (active or latent) infection or risk factor for TB
* active bacterial, fungal or viral infection at the time of enrollment or history of recurrent infections
* suspected or proven immunocompromised state
* live vaccinations within 3 months prior to randomization visit or live vaccinations planned during the trial
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