TY - JOUR
T1 - A randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI
AU - Adlam, David
AU - Zarebinski, Maciej
AU - Uren, Neal G
AU - Ptaszynski, Pawel
AU - Oldroyd, Keith G
AU - Munir, Shahzad
AU - Zaman, Azfar
AU - Contractor, Hussain
AU - Kiss, Róbert Gábor
AU - Édes, István
AU - Szachniewicz, Joanna
AU - Nagy, Gergely Gyorgy
AU - Garcia, Mario J
AU - Tomcsanyi, János
AU - Irving, John
AU - Sharp, Andrew S P
AU - Musialek, Piotr
AU - Lupkovics, Géza
AU - Shirodaria, Cheerag
AU - Selvanayagam, Joseph B
AU - Quinn, Pauline
AU - Ng, Leong
AU - Roth, Mark
AU - Insko, Michael A
AU - Haber, Ben
AU - Hill, Stephen
AU - Siegel, Lori
AU - Tulloch, Simon
AU - Channon, Keith M
N1 - Copyright © 2021. Published by Elsevier B.V.
PY - 2022/1/15
Y1 - 2022/1/15
N2 - 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.
AB - 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.
U2 - 10.1016/j.ijcard.2021.11.016
DO - 10.1016/j.ijcard.2021.11.016
M3 - Article
C2 - 34774885
SN - 0167-5273
VL - 347
SP - 1
EP - 7
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -