A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute stemi patients undergoing primary PCI

David Adlam, Maciej Zarebinski, Neal G. Uren, Pawel Ptaszynski, Keith G. Oldroyd, Shahzad Munir, Azfar Zaman, Hussain Contractor, Róbert Gábor Kiss, István Édes, Joanna Szachniewicz, Gergely Gyorgy Nagy, Mario J. Garcia, János Tomcsanyi, John Irving, Andrew S. P. Sharp, Piotr Musialek, Géza Lupkovics, Cheerag Shirodaria, Joseph B. SelvanayagamPauline Quinn, Leong Ng, Mark Roth, Michael A. Insko, Ben Haber, Stephen Hill, Lori Siegel, Simon Tulloch, Keith M. Channon (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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 PPCI in acute STEMI, is feasible, safe, and shows potential efficacy. A larger trial is justified to test the effects of FDY-5301 on acute ischemia-reperfusion injury and clinical outcomes.

    Clinical Trial Registration: CT.govNCT03470441; EudraCT 2017-000047-41.

    Original languageEnglish
    Pages (from-to)1-7
    Number of pages7
    JournalInternational Journal of Cardiology
    Volume347
    Early online date11 Nov 2021
    DOIs
    Publication statusPublished - 15 Jan 2022

    Keywords

    • Myocardial infarction
    • Primary PCI
    • Reperfusion injury

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