Table 2 Clinical trials with immunomodulatory therapeutics for cardiovascular diseases
From: The immune system in cardiovascular diseases: from basic mechanisms to therapeutic implications
Study names | Drugs | Mechanism of action | Targets | Phase | Patient cohort | Primary endpoints | Main outcomes | NCT number |
|---|---|---|---|---|---|---|---|---|
Lodoco2 (2020)690 | Colchicine | Microtubule inhibitor | TUBB | Phase3 | Patients with CAD | MACE | Low-dose colchicine significantly reduced cardiovascular events. | ACTRN12614000093684 |
COLCOT (2019)47 | Colchicine | Microtubule inhibitor | TUBB | Phase3 | Patients with MI | MACE | 0.5 mg daily colchicine significantly reduced ischemic cardiovascular risk | NCT02551094 |
NA | Colchicine | Microtubule inhibitor | TUBB | Phase 2 | Patients with HFpEF | Change in hs-CRP | NA | NCT04857931 |
NA | Colchicine | Microtubule inhibitor | TUBB | NA | Patients with AAA | Changes in maximum diameter of AAA | NA | NCT05361772 |
NA | Colchicine | Microtubule inhibitor | TUBB | Phase 3 | Patients with CHD requiring PCI | MACE | NA | NCT06472908 |
COCS (2024) | Colchicine | Microtubule inhibitor | TUBB | Phase4 | Patients awaiting elective cardiac surgery (CABG/AVR) | Postoperative atrial fibrillation incidence | NA | NCT04224545 |
CIRT (2018)653 | Methotrexate | Broad immuno—suppression dihydrofolate reductase inhibitor | A2AR | Phase3 | Patients with prior MI or multivessel CAD by angiography | MACE | Methotrexate didn’t reduce IL-1β, IL-6, CRP, or cardiovascular events | NCT01594333 |
NA | Methotrexate | Broad immuno—suppression dihydrofolate reductase inhibitor | A2AR | Phase4 | Patients with RA | Change in peripheral SBP | NA | NCT03254589 |
CAPRI (2020)654 | Ciclosporin | Broad immuno—suppression Calcineurin inhibitors | MPTP | Phase2 | Patients with STEMI and undergoing PCI | Change in infarct size | Single ciclosporin bolus had no effect on infarct size or LV remodeling | NCT02390674 |
Mohd Ali et al. (2018)655 | Sirolimus | Broad immuno—suppression mTOR inhibitors | FKBP 12 | Phase1 | Patients with coronary DES restenosis | Late lumen loss | Novel SCB vs. proven PCB for coronary DES ISR shows similar angiographic outcomes | NCT02996318 |
ORAR656 | Rapamycin | mTOR inhibitor | mTOR | Phase3 | Patients with BMS implantation | Cost differences in revascularization for de novo lesions | No outcome difference between oral rapamycin + BMS and DES for de novo lesions | NCT00552669 |
CLEVER--ACS657 | Everolimus | mTOR inhibitor | mTOR | Phase1/2 | Patients with STEMI | MI size measured by MRI | Treatment didn’t reduce MI size or MVO at 30 days | NCT01529554 |
CANTOS (2017)46 | Canakinumab | Anti--interleukin-1β antibodies | IL-1β | Phase 3 | Patients with MI | MACE | 150 mg canakinumab every 3 months significantly lowered recurrent cardiovascular events versus placebo | NCT01327846 |
VCUART3 (2020)659 | Anakinra | IL-1 receptor antagonist | IL-1Ra | Phase 2 | Patients with STEMI | The AUC for hsCRP | Compared to placebo, it significantly reduces the systemic inflammatory response | NCT01950299 |
MAGiC-ART(2020) | Anakinra | IL-1 receptor antagonist | IL-1Ra | Phase 2 | Patients with cardiac sarcoidosis | Change in inflammation marker | NA | NCT04017936 |
Myachikova et al. 660 | Goflikicept | IL-1 inhibitor | IL-1β | Phase 2/3 | Patients with idiopathic recurrent pericarditis | Time to first pericarditis recurrence was evaluated | Goflikicept reduced recurrence risk vs. placebo | NCT04692766 |
Sayed et al.658 | Xilonix | IL-1α inhibitor | IL-1α | Phase 2 | Patients after PCI | Target vessel restenosis, time to restenosis, and MACE incidence | At 12 months, no significant difference in MACE or target vessel restenosis between groups | NCT01270945 |
RESCUE 661 | Ziltivekimab | IL-6-targeting monoclonal antibody | IL-6 | Phase 2 | Patients with moderate to severe CKD | 12-week change in hs-CRP | Ziltivekimab markedly reduced atherosclerosis--related inflammation and thrombosis biomarkers | NCT03926117 |
ARTEMIS (2024) | Ziltivekimab | IL-6-targeting monoclonal antibody | IL-6 | Phase3 | Patients with AMI | Time to first 3-component MACE | NA | NCT06118281 |
ATHENA (2024) | Ziltivekimab | IL-6-targeting monoclonal antibody | IL-6 | Phase3 | Patients with HF | Change in KCCQ-CSS | NA | NCT06200207 |
ASSAIL-MI (2021)663 | Tocilizumab | IL-6-targeting monoclonal antibody | IL-6 | Phase 2 | Patients with STEMI within 6 h undergoing PCI | Myocardial salvage index (%) | Tocilizumab increased myocardial salvage in patients with acute STEMI | NCT03004703 |
Kleveland. et al. 662 | Tocilizumab | IL-6-targeting monoclonal antibody | IL-6 | Phase 2 | Patients with NSTEMI | Between-group AUC difference for hs-CRP (days 1–3) | Tocilizumab attenuated the inflammatory response | NCT01491074 |
IMICA (2021)664 | Tocilizumab | IL-6-targeting monoclonal antibody | IL-6 | Phase2 | Patients with out-of-hospital cardiac arrest | Reduction in CRP levels at 72 h | Tocilizumab reduced systemic inflammation and myocardial injury in comatose patients post-cardiac arrest. | NCT03863015 |
NA | NT-0796 | NLRP3 inhibitor | NLRP3 | Phase 2 | Patients with BMI ≥ 30 and ≤40 kg/m2 | Change in hsCRP levels | NA | NCT06129409 |
NA | DFV890 | NLRP3 inhibitor | NLRP3 | Phase 2 | Patients with MI (ages 18–85, BMI 18–45 kg/m², hsCRP ≥ 2 mg/L) | Serum levels of IL-6 and IL-18 | NA | NCT06031844 |
Wohlford et al. 667 | Dapansutrile | Selective NLRP3 Inflamma--some Inhibitor | NLRP3 | Phase 1b | Patients with stable systolic HF, LVEF ≤ 40%, NYHA II-III symptoms | AEs | 14-day dapansutrile treatment was safe and well-tolerated in stable HFrEF patients | NCT03534297 |
CATCH-AMI (2013) | Balixafortide (POL6326) | CXCR4 antagonist | CXCR4 | Phase IIa | Patients with reperfused STEMI | Change in LVEF determined by MRI | NA | NCT01905475 |
NA | Etanercept | TNF-α inhibitor | TNF-α | Phase4 | Patients with AMI | MACE | NA | NCT01372930 |
Colombo et al. 669 | Bindarit | Selective inhibitor of monocyte chemotactic protein-1 (MCP-1/CCL2) | MCP-1/CCL2 | Phase IIa | Patients with coronary BMS | In-segment late loss | Bindarit significantly reduced in-stent late loss, indicating potential vessel wall benefits post-angioplasty | NCT01269242 |
NA | BRB-002 | Novel Anti-CD47 Molecule | CD47 | Phase 1 | Healthy male volunteers | To evaluate the safety and tolerability of BRB-002 | NA | ACTRN12624000405516 |
NA | Atibuclimab | Chimeric monoclonal antibody targeting CD14 | CD14 | Phase 1b | Patients with ACM | Safety and efficacy of the drug | NA | NCT06275893 |
Chen et al. 675 | RTP-026 | Annexin-A1 analog | FPR2 | Phase2 | Patients with STEMI undergoing PCI, chest pain <12 h, NLR 7-17 | cTNT/CK-MB at 24 hours | NA | NCT06465303 |
Hernández-Jiménez et al. 671 | ApTOLL | Toll-like receptor 4 antagonist | TLR4 | Phase1 | Health male volunteers | Assess safety and pharmacokinetics of 30-min IV ApTOLL infusion | No ApTOLL accumulation, confirming safety and supporting clinical trials | NCT04742062 |
SATELLITE (2023)670 | AZD4831 | Myelo--peroxidase inhibitor | Mpo | Phase2 | Patients with HFpEF | Myeloperoxidase specific activity | AZD4831 was safe and effectively inhibited myeloperoxidase. | NCT03756285 |
RESTORE (2022) | OPL-0301 | S1PR1 agonist | S1PR1 | Phase 2 | Patients with acute STEMI | Infarct size by CMR at Day 90 | NA | NCT05327855 |
HUCV002-01 (2022)684 | αGCDC | α-galactosylceramide-pulsed dendritic cells (αGCDCs) | INKT cell | Phase 2 | Patients with CHF | Change in LVEF from baseline to 24 weeks | NA | jRCT2073210116 |
Hare et al. (2005)680 | Adult hMSCs | Cell-based immuno--modulators | DMMI | Phase1 | Patients with MI | AEs rates in 0.5, 1.6, and 5.0 million MSC/kg dose cohorts vs. placebo | Similar adverse event rates between hMSC and placebo groups | NCT00114452 |
Lee et al. 681 | SEED-MSC (BM-MSCs) | Cell-based immuno--modulators | DMAMI | Phase2/3 | Patients with AMI | Absolute changes in global LVEF by SPECT | Safe and tolerable, showing modest LVEF improvement at 6 months by SPECT | NCT01392105 |
Chullikana et al. 685 | Stempeuce (BM-MSCs) | Cell-based immuno--modulators | DMAMI | Phase1/2 | Patients with STEMI | AEs and ECG parameters | Safe and well-tolerated IV in AMI patients 2 days post-PCI | NCT00883727 |
Butler (2016)686 | aMBMC | Cell-based immuno--modulators | NICM | Phase 2a | Patients with non-ischemic Heart Failure | Safety by number of AEs | Safe, immunomodulatory effects, with improved health status and functional capacity | NCT02467387 |
NA | BM-MSCs | Cell-based immuno--modulators | DMAMI | Phase3 | Patients with AMI | Change in LVEF | NA | NCT01652209 |
TRIDENT (2017)687 | hMSC | Cell-based immuno--modulators | ICM | Phase 2 | Patients with ischemic cardiomyopathy | Number of Participants With TE-SAEs | 100 million dose increased ejection fraction; both doses reduced scar size | NCT02013674 |
TAC-HFT-II (2020) | hmsc/hCSC | Cell-based immuno--modulators | DMMI | Phase1/2 | Patients with chronic ischemic LV dysfunction and HF post-MI | Incidence of any TE-SAEs | NA | NCT02503280 |
WJ-MSC-AMI (2015)682 | WJMSCs | Cell-based immuno--modulators | DMSTEMI | Phase2 | Patients with AMI | Myocardium metabolic and perfusion measurements, global LVEF by echocardiography | Intracoronary WJMSCs safe and effective in AMI, clinically relevant therapy | NCT01291329 |
RIMECARD (2016)688 | UC-MSC | Cell-based immuno--modulators | LV function in HFrEF | Phase1/2 | Patients with compensated HF (dilated phase) | Change in global LVEF | IV UC-MSCs safe in stable HF with reduced LVEF | NCT01739777 |
HUC-HEART Trial 689 | HUC-MSCs | Cell-based immuno--modulators | ICM | Phase1/2 | Patients with chronic ischemic CM | Ventricular remodeling | Intramyocardial HUC-MSCs effective in CIC | NCT02323477 |
NA | UC-MSCs | Cell-based immuno--modulators | DMMI | Phase1 | Patients with MI | MACE | NA | NCT03902067 |
NA | Clinical-grade WJ-MSCs | Cell-based immuno--modulators | DMSTEMI | Phase1/2 | Patients with STEMI | MI size | NA | NCT03533153 |
Qayyum. et al. 683 | ADSCS | Cell-based immuno--modulators | LV function in HFrEF | Phase2 | Patients with HFrEF | Change in LVESV | Safe but no improvement in myocardial function or symptoms | NCT03092284 |
