Table 3.
Ongoing randomized controlled trials targeting the immune system in atherosclerosis
| Trial name (number) | Agent | Drug target | Trial design | Patient cohort | Primary end point | Ref. |
|---|---|---|---|---|---|---|
| OXI (NCT02648464) | Hydroxychloroquine | Broad immunosuppression | Phase IV | 125 patients with MI | Rate of cardiovascular adverse events (MI, death, hospitalization for unstable angina and heart failure) | 252 |
| CHANGAN (NCT02874287) | Hydroxychloroquine | Broad immunosuppression | Phase IV | 35 patients with CAD and hsCRP >1 mg/l | Change in fasting hsCRP level | 253 |
| LILACS (NCT03113773) | Low-dose IL-2 | Induces expansion of regulatory T cell numbers | Phase I–II | 41 patients with a history of CAD or acute coronary syndrome | Safety, tolerability and circulating regulatory T cell levels | 254 |
| IVORY (NCT04241601) | Low-dose IL-2 | Induces expansion of regulatory T cell numbers | Phase II | 60 patients with ACS and hsCRP >2 mg/l | Change in vascular inflammation, as measured by FDG PET–CT | 255 |
| NCT04762472 | Montelukast | Leukotriene receptor | Phase IV | 200 adults asymptomatic for atherosclerotic disease and exposed to air pollution | Subclinical atherosclerosis (as measured by brachial flow-mediated dilatation, carotid intima–media thickness and blood inflammatory markers) | 256 |
| NCT04616872 | Methotrexate delivered in LDL-like nanoparticles | Broad immunosuppression | Phase II–III | 40 patients with multivessel CAD and hsCRP >2 mg/l | Reduction in plaque volume, measured by CTA | 257 |
| SARIPET (NCT04350216) | Sarilumab | Monoclonal antibody against IL-6 receptor | Phase IV | 20 patients with active rheumatoid arthritis and CRP levels >1 mg/dl | Changes in carotid atheroma plaque assessed by ultrasonography | 258 |
| PAC-MAN (NCT04148833) | Paclitaxel | Proliferation | Phase II–III | 40 patients with CAD | Low-attenuation plaque volume measured by CTA | 259 |
| GOLDILOX (NCT04610892) | MEDI6570 | Antibody against LOX1 receptor (blocks uptake of oxidized LDL) | Phase IIb | 792 patients with a history of MI | Non-calcified plaque volume measured by CTA | 260 |
| CLEAR-Synergy (NCT03048825) | Colchicine | Broad immunosuppression | Phase III | 7,000 patients with MI | MACE | 261 |
| CONVINCE (NCT02898610) | Colchicine | Broad immunosuppression | Phase III | 2,623 patients with ischaemic stroke or at high risk of transient ischaemic attack | Recurrence of non-fatal ischaemic stroke or non-fatal MACE, or vascular-related death | 262 |
| ZEUS (NCT05021835) | Ziltivekimab | Monoclonal antibody against IL-6 | Phase III | 6,200 patients with chronic kidney disease and CRP ≥2 mg/l | Time to first MACE | 121 |
ACS, acute coronary syndrome; CAD, coronary artery disease; CRP, C-reactive protein; CTA, computed tomography angiography; FDG, fluorodeoxyglucose; hsCRP, high-sensitivity C-reactive protein; LOX1, lectin-like oxidized LDL receptor 1; MACE, major adverse cardiovascular events; MI, myocardial infarction.