Comparison of Antiplatelet Effect and Safety of Clopidogrel Napadisilate with Clopidogrel Bisulfate in Stroke Patients: Multi-Center, Randomized, Open-Label, Phase IV, Non-Inferiority Clinical Trial

摘要

Background: Clopidogrel napadisilate has better clopidogrel stability than clopidogrel bisulfate. Our trial’s objective wasto compare the efficacy and safety of clopidogrel napadisilate with clopidogrel bisulfate in participants with ischemic stroke. Methods: The study was a phase 4, 4-week, randomized, parallel-group, non-inferiority trial. Patients are randomized to receive either clopidogrel napadisilate 75 mg or clopidogrel bisulfate 75 mg. The primary study endpoint was change from baseline in P2Y12 percent inhibition at week 4. The primary analysis was conducted in the per-protocol population. Noninferiority was confirmed if the lower limit of the 95% confidence interval (CI) of the treatment difference was more than or equal to –9.0% points. The secondary endpoint was change in P2Y12 reactivity units (PRU). At a final visit, all adverse events were recorded. Results: Sixty-one participants were randomly assigned clopidogrel napadisilate and 60 were randomly assigned clopidogrel bisulfate. Thirty-nine participants in the clopidogrel napadisilate group and 39 in the clopidogrel bisulfate group were analyzed for the primary endpoint. At 4 weeks, mean percent inhibition had increased in both treatment groups. The estimated mean change from baseline was 22.3% with clopidogrel napadisilate and 21.4%with clopidogrel bisulfate; the estimated treatment difference of 0.9% (95% CI, –8.6 to 10.4) confirmed the non-inferiority of clopidogrel napadisilate to clopidogrel bisulfate. The mean reduction in PRU and rates of adverse events were not significantly different between treatments.Conclusion: Clopidogrel napadisilate was noninferior to clopidogrel bisulfate as assessed by change in platelet inhibition.Rates of adverse events were similar between the two groups. Therefore, clopidogrel napadisilate can be a suitable alternative to clopidogrel bisulfate in ischemic stroke patients.