Bendavia reduces ROS generation, protects cardiolipin, and preserves mitochondrial integrity and function in animal models of ischemia/reperfusion. The goal of this phase 2 trial was to assess the safety and efficacy of bendavia in acute myocardial infarction in humans.
Material and methods
Randomized, double-blind, placebo-controlled study.Patients were randomized in a 1:1 fashion to either bendavia 0.05 mg/kg/hr (n = 58) or placebo (n = 60). Inclusion criteria: First anterior ST-segment elevation myocardial infarction (STEMI) with TIMI 0/1 flow in the proximal or mid LAD and with anticipated symptoms to PCI
Patient characteristics: Mean patient age: 60 years, females 28%, diabetics 10%, ischemia time: 151 minutes, left anterior descending artery (LAD) area at risk: 85%, aspiration thrombectomy prior to percutaneous coronary intervention (PCI): 68%.
The primary outcome was similar in the bendavia and placebo arms: 217.4 vs. 266.6 (ns). Secondary outcomes: AUC troponin I at 6 hours: 144.6 vs. 139.3, ns. Complete ST-segment resolution immediately post-PCI: 14.6% vs. 22%, p > 0.05. Infarct volume at day 4: 43.1 vs. 48.4, ns. Left ventricular ejection fraction at day 4: 44.0% vs. 41.9%, ns. Infarct volume at day 30: 30.1 vs. 31.5. Left ventricular ejection fraction at day 30: 44.8% vs. 46.1%, ns. Complete ST-segment resolution immediately after PCI (14.6% vs 22%, ns) or at 24 hours (53.6% vs 50.9%, ns). TIMI 3 flow after PCI: 88.3% vs 87.1%, ns). Death/new-onset chronic heart failure rehospitalization at 30 days: 22.4% vs. 28.3%, ns, and at 6 months: 25.9% vs 28.3%, ns. During the 8 hours during / following Bendavia administration, there was a trend towards reduced symptomatic heart failure (8.6% vs. 18.3%, p=0.18).
The results of this trial indicate that bendavia, a novel agent to prevent mitochondrial dysfunction, and thus potentially reperfusion injury, does not reduce infarct size compared with placebo in patients with anterior STEMI due to proximal/mid occlusion of the LAD. Further phase 3 trials are ongoing. The hypothesis generating data that demonstrated a trend toward a favorable reduction in CHF symptoms in the 8 hours during / following Bendavia administration is being prospectively evaluated at comparable and higher doses in an ongoing trials of patients with systolic heart failure (HFREF) .