| Title: |
A randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI |
| Authors: |
Adlam, D; Zarebinski, M; Uren, NG; Ptaszynski, P; Oldroyd, KG; Munir, S; Zaman, A; Contractor, H; Kiss, RG; Édes, I; Szachniewicz, J; Nagy, GG; Garcia, MJ; Tomcsanyi, J; Irving, J; Sharp, ASP; Musialek, P; Lupkovics, G; Shirodaria, C; Selvanayagam, JB; Quinn, P; Ng, L; Roth, M; Insko, MA; Haber, B; Hill, S; Siegel, L; Tulloch, S; Channon, KM |
| Publisher Information: |
Elsevier |
| Publication Year: |
2022 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Background Ischemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS). FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant. We tested the feasibility, safety and potential utility of FDY-5301 as a treatment to limit ischemia-reperfusion injury, in patients with first-time STEMI undergoing emergency PPCI. Methods STEMI patients (n = 120, median 62 years) presenting within 12 h of chest pain onset were randomized at 20 PPCI centers, in a double blind Phase 2 clinical trial, to receive FDY-5301 (0.5, 1.0 or 2.0 mg/kg) or placebo prior to reperfusion, to evaluate the feasibility endpoints. Participants underwent continuous ECG monitoring for 14 days after PPCI to address pre-specified cardiac arrhythmia safety end points and cardiac magnetic resonance imaging (MRI) at 72 h and at 3 months to assess exploratory efficacy end points. Results Intravenous FDY-5301 was delivered before re-opening of the infarct-related artery in 97% participants and increased plasma iodide levels ~1000-fold within 2 min. There was no significant increase in the primary safety end point of incidence of cardiac arrhythmias of concern. MRI at 3 months revealed median final infarct sizes in placebo vs. 2.0 mg/kg FDY-5301-treated patients of 14.9% vs. 8.5%, and LV ejection fractions of 53.9% vs. 63.2%, respectively, although the study was not powered to detect statistical significance. In patients receiving FDY-5301, there was a significant reduction in the levels of MPO, MMP2 and NTproBNP after PPCI, but no reduction with placebo. Conclusions Intravenous FDY-5301, delivered immediately prior to ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.ijcard.2021.11.016 |
| DOI: |
10.1016/j.ijcard.2021.11.016 |
| Availability: |
https://doi.org/10.1016/j.ijcard.2021.11.016; https://ora.ox.ac.uk/objects/uuid:d2a2e59f-347e-481b-8dad-cb3ccd8b701d |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) |
| Accession Number: |
edsbas.4EB5186A |
| Database: |
BASE |