Table 1.
Overview of recent trials on anti-thromboinflammatory strategies
| Name | NCT/ISRCTN | Design | Indication | Drug | Target | Phase | Status | Outcome |
|---|---|---|---|---|---|---|---|---|
| MR CLEAN-MED | ISRCTN76741621 [198] | Interventional, randomized, open label, blinded endpoint | Acute ischemic stroke | EVT +/- UFH +/- ASA | AT III; COX-1/-2 | III | Completed /Halted | No benefit to mRS; increase in sICH |
| ARAIS | NCT03740958 [207] | Interventional, prospective randomized, open label, blinded endpoint | Acute ischemic stroke | Argatroban +/- rt-PA | Thrombin | IV | Completed | No benefit to mRS |
| PACIFIC-STROKE | NCT04304508 [214] | Interventional, randomized, quadruple-blinded, placebo-controlled | Acute non- cardioembolic ischemic stroke | Asundexian (BAY 2433334) +/- antiplatelet therapy | FXIa | II | Completed | No overall benefit |
| AZALEA-TIMI 71 | NCT04755283 [215] | Interventional, randomized, triple-blinded | Atrial Fibrillation; Stroke | Abelacimab (MAA868) or Rivaroxaban | FXI or FX | II | Active (not recruiting) | n.a. |
| LILAC | NCT05712200 [215] | Interventional, randomized, double-blinded, placebo-controlled | Atrial Fibrillation | Abelacimab (MAA868) | FXI/FXIa | III | Recruiting | n.a. |
| AXIOMATIC-SSP | NCT03766581 [216] | Interventional, randomized, quadruple-blinded, placebo-controlled | Acute ischemic stroke; transient ischemic attack | Milvexian (BMS-986177) + Clopidogrel + ASA | FXIa | II | Completed | Results pending |
| ACTIMIS | NCT03803007 [217] | Interventional, randomized, triple-blinded, placebo-controlled | Acute ischemic stroke | Glenzocimab (ACT017) + rt-PA + / - Thrombectomy | GPVI | Ib/IIa | Completed | Safety confirmed |
| GREEN | NCT05559398 [217] | Interventional, randomized, quadruple-blinded, placebo-controlled | Acute Stroke; Ischemic Stroke | Glenzocimab (ACT017) + EVT | GPVI | II/III | Not yet recruiting | n.a. |
| ACTISAVE | NCT05070260 [217] | Interventional, triple-blinded, randomized, placebo-controlled | Acute ischemic stroke | Glenzocimab (ACT017) + rt-PA + / - Thrombectomy | GPVI | II/III | Recruiting | n.a. |
| ReMEDy1 | NCT03290560 [219] | Interventional, randomized, double-blinded, placebo-controlled | Acute ischemic stroke | DM199 | KKS | II | Completed | Results pending |
| ReMEDy2 | NCT05065216 | Interventional, randomized, double-blinded, placebo-controlled | Acute Stroke; Ischemic Stroke; Stroke | DM199 | KKS | II/III | Active (not recruiting) | n.a. |
| NCT04742062 [221] | Interventional, randomized, triple-blinded, placebo-controlled | Stroke | ApTOLL | TLR4 | I | Completed | Safety confirmed | |
| NCT04734548 [220] | Interventional, prospective, randomized, quadruple-blinded, placebo-controlled | Stroke; acute stroke; ischemic stroke | ApTOLL + EVT (+/- rt-PA) | TLR4 | Ib/IIa | Completed | Final results pending | |
| CANTOS | NCT01327846 [225] | Interventional, randomized, triple-blinded, placebo-controlled | Atherosclerosis | Canakinumab | IL-1β | III | Completed | Reduction of cardiovascular events and hsCRP |
Abbreviations: ACTIMIS Acute Ischemic Stroke Interventional Study, ACTISAVE Adaptive Efficacy and Safety Study of Glenzocimab Used as an add-on Therapy on Top of Standard of Care in the 4.5 Hours Following an Acute Ischemic Stroke, ARAIS Argatroban Plus rt-PA for Acute Ischemic Stroke, ASA acetylsalicylic acid, AT antithrombin, AZALEA-TIMI 71 Safety and Tolerability of Abelacimab (MAA868) vs. Rivaroxaban in Patients With Atrial Fibrillation, CANTOS Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events), COX cyclooxygenase, EVT endovascular treatment, F(a) (activated) coagulation factor, GP glycoprotein, GREEN Glenzocimab for REperfusion in the Setting of Endovascular Therapy for Brain infarctioN, hsCRP high-sensitivity C-reactive protein, IL interleukin, ISRCTN international standard randomised controlled trial number (see: https://www.isrctn.com/), KKS kallikrein/kinin system, LILAC Study to evaLuate the effIcacy and Safety of abeLacimab in High-risk Patients With Atrial Fibrillation Who Have Been Deemed Unsuitable for Oral antiCoagulation, A Study on BMS-986177 for the Prevention of a Stroke in Patients Receiving Aspirin and Clopidogrel, MR CLEAN-MED, Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands: the effect of periprocedural MEDication: heparin, antiplatelet agents, both or neither, mRS modified Rankin Scale, NCT national clinical trial (see: https://clinicaltrials.gov/); PACIFIC-STROKE, Study to Gather Information About Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following a Recent Non Cardioembolic Ischemic Stroke Which Occurs When a Blood Clot Has Formed Somewhere in the Human Body (But Not in the Heart) Travelled to the Brain; ReMEDy1, Evaluation to Assess Safety and Tolerability of DM199 in Subjects With Acute Ischemic Stroke, ReMEDy2 Treatment of Acute Ischemic Stroke, rt-PA recombinant tissue plasminogen activator, sICH symptomatic intracerebral hemorrhage, TLR toll-like receptor, UFH unfractionated heparin