1. SUPPORT-1 (Subjects Undergoing PCI and Perioperative Reperfusion Treatment): A Prospective, Randomized Trial of CMX-2043 in Patients Undergoing Elective Percutaneous Coronary Intervention.
- Author
-
Tcheng JE, Gibson M, Krucoff MW, Patel MR, Ajit M, Hiremath J, Ponde C, Ramsaran E, Clark G, Lader AS, and Beeuwkes R 3rd
- Subjects
- Aged, Biomarkers blood, Cardiovascular Agents adverse effects, Cardiovascular Agents pharmacokinetics, Coronary Artery Disease diagnostic imaging, Creatine Kinase, MB Form blood, Dipeptides adverse effects, Dipeptides pharmacokinetics, Double-Blind Method, Female, Humans, India, Male, Middle Aged, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Necrosis, Prospective Studies, Thioctic Acid adverse effects, Thioctic Acid pharmacokinetics, Thioctic Acid therapeutic use, Time Factors, Treatment Outcome, Troponin T blood, United States, Angioplasty, Balloon, Coronary adverse effects, Cardiovascular Agents therapeutic use, Coronary Artery Disease therapy, Dipeptides therapeutic use, Myocytes, Cardiac drug effects, Thioctic Acid analogs & derivatives
- Abstract
Objective: The natural molecule α-lipoic acid has been shown to be partially cytoprotective through antioxidant and antiapoptotic mechanisms. To obtain an initial assessment of the safety and potential efficacy of a synthetic derivative, CMX-2043, in preventing ischemic complications of percutaneous coronary intervention (PCI) we conducted the Subjects Undergoing PCI and Perioperative Reperfusion Treatment (SUPPORT-1) trial, the first patient experience with this agent., Methods and Results: SUPPORT-1 was a phase 2a, 6-center, international, placebo-controlled, randomized, double-blind trial. A total of 142 patients were randomized to receive a single intravenous bolus dose of drug or placebo administered 15-60 minutes before PCI. Cardiac biomarker assessments included serial measurements of creatine kinase myocardial band (CK-MB) at 6, 12, 18, and 24 hours after PCI and a single measurement of troponin T (TnT) at 24 hours. Peak concentrations of CK-MB and TnT were significantly reduced in the 2.4 mg/kg group compared with placebo (P = 0.05 and 0.03, respectively). No subject administered 2.4 mg/kg of CMX-2043 had an increase of CK-MB to ≥3X upper limit of normal versus 16% for placebo (P = 0.02); 16% of the 2.4-mg/kg dose group developed an elevation of TnT to ≥3X upper limit of normal versus 39% in the placebo group (P = 0.05). No drug-related serious adverse events were observed in any group., Conclusion: These data suggest that CMX-2043 may reduce PCI periprocedural myonecrosis and support further clinical evaluation of this novel agent for its potential cytoprotective effects.
- Published
- 2020
- Full Text
- View/download PDF