1. A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI
- Author
-
István Édes, Andrew S.P. Sharp, Neal G. Uren, Michael A Insko, János Tomcsányi, Shahzad Munir, Leong L. Ng, Ben Haber, Azfar Zaman, Keith M. Channon, Mario J. Garcia, Géza Lupkovics, Keith G. Oldroyd, David Adlam, John Irving, Piotr Musialek, Róbert Gábor Kiss, Hussain Contractor, Stephen Hill, Mark B. Roth, Simon Tulloch, Paweł Ptaszyński, P A Quinn, Lori Siegel, Cheerag Shirodaria, Joseph B. Selvanayagam, Maciej Zarębiński, Gergely Nagy, and Joanna Szachniewicz
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Placebo ,Chest pain ,Percutaneous Coronary Intervention ,Double-Blind Method ,Cardiac magnetic resonance imaging ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Anterior Wall Myocardial Infarction ,Ejection fraction ,medicine.diagnostic_test ,business.industry ,Percutaneous coronary intervention ,Arrhythmias, Cardiac ,medicine.disease ,Clinical trial ,Treatment Outcome ,Conventional PCI ,Cardiology ,ST Elevation Myocardial Infarction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - 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.gov NCT03470441 ; EudraCT 2017-000047-41
- Published
- 2022