Efficacy and safety of clevidipine emulsion injection compared with nicardipine in patients with hypertensive emergencies: a randomized, single-blind, positive-parallel-controlled, phase III clinical trial

Background: Clevidipine emulsion injection is an ultra-short-acting, intravenous calcium-channel blocker that produces a rapid and transient antihypertensive effect. Methods: This is a multicenter, randomized, single-blind, parallel, positive-controlled, noninferiority phase III clinical trial comparing the efficacy and safety of clevidipine and nicardipine in hypertensive emergencies. Participants were randomly assigned in a 1 : 1 ratio to the experimental group (clevidipine emulsion injection) or the positive-control group (nicardipine), and standard safety data were collected. Results: In the per-protocol set (PPS), the primary endpoint showed that 100.0% of patients in the clevidipine group achieved a 15–25% reduction in systolic blood pressure from baseline within 30 min after dosing, compared with 95.9% in the nicardipine group. The absolute difference between the two proportions was 4.1% [95% confidence interval (CI): 0.58, 7.62], with the lower bound exceeding the noninferiority margin of –10%. Secondary endpoints revealed that the median time to reach the target systolic blood pressure (defined as a 15–25% reduction from baseline) was 9.0 (9.0, 12.0) minutes for clevidipine versus 12.0 (12.0, 15.0) minutes for nicardipine, and the between-group difference was statistically significant ( P < 0.0001). The proportions of patients who successfully transitioned to oral antihypertensive therapy within 6 h after study drug discontinuation were 96.83% for clevidipine and 95.90% for nicardipine, with no statistically significant difference ( P = 0.7459). In the safety set (SS), the safety endpoint showed that the proportion of patients whose systolic blood pressure fell by >25% from baseline within 3 min after dosing was 0.00% for clevidipine and 0.79% for nicardipine, with no statistically significant difference ( P = 0.4980). The overall incidence of adverse events was similar between clevidipine and nicardipine. Conclusions: Clevidipine has similar therapeutic effects and safety compared with the nicardipine. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04670809.