Comparison of antiplatelet effect and safety of clopidogrel napadisilate with clopidogrel bisulfate in stroke patients: multicenter, randomized, open-label, phase 4, non-inferiority clinical trial

Abstract

Objective:

Clopidogrel napadisilate has better chemical stability than clopidogrel bisulfate. Our trial’s objective was to compare the efficacy and safety of clopidogrel napadisilate with clopidogrel bisulfate in participants with ischemic stroke.

Research design and methods:

The study was a phase 4, 4 week, randomized, parallel-group, non-inferiority trial. Patients with ischemic stroke were randomized to receive either clopidogrel napadisilate 75 mg or clopidogrel bisulfate 75 mg. The primary study endpoint was change from baseline in P2Y12 percentage inhibition at week 4. The primary analysis was conducted in the per-protocol population. Non-inferiority was confirmed if the lower limit of the 95% confidence interval (CI) of the treatment difference was greater than or equal to −9.0% points.

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 P2Y12 percentage 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.

Conclusions:

Clopidogrel napadisilate was non-inferior to clopidogrel bisulfate as assessed by change in P2Y12 percentage inhibition. Rates of adverse events were similar between the two groups. Therefore, clopidogrel napadisilate is a useful alternative option for the dosing of ischemic stroke patient populations.

Keywords: :

• Clopidogrel bisulfate
• Clopidogrel napadisilate
• Randomized controlled trial
• Stroke

Transparency

Declaration of funding

This research was financially sponsored by Hanmi Pharmaceutical Co. Ltd, Seoul, Republic of Korea, who paid for patient visits, testing, and medication. The study was an investigator-initiated trial, and the sponsor had no involvement in the study design, collection, analysis, and interpretation of data, or writing the manuscript.

Declaration of financial/other relationships

K.K. has disclosed that he has received consulting fees from Sanofi-Aventis Korea Co. Ltd and has participated in clinical investigations of antihypertensive and antiplatelet agents sponsored by Hanmi Pharmaceutical Co. Ltd. S.-J.L., H.-J.K., S.-H.K., and B.K.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Notes

*Pidogul is a registered trade name of Hanmi Phamaceuticals Co. Ltd, Seoul, Republic of Korea.

†Plavix is a registered trade name of Sanofi-Aventis, Paris, France.