Assessment of the efficacy and tolerability of clopidogrel napadisilate in Korean patients with coronary stenting: a multicenter, prospective, open-label, randomized trial

Abstract

Objective:

Clopidogrel is indicated for the treatment and prevention of peripheral vascular, cerebrovascular, and coronary artery diseases. This clinical trial was designed to demonstrate that clopidogrel napadisilate (CN) is not inferior to clopidogrel bisulfate (CB) with respect to its effectiveness in inhibiting platelet aggregation.

Methods:

This 4 week multi-center, prospective, open-label, randomized trial was conducted at five clinical centers in South Korea. Patients were randomized into the 75 mg CN group or the 75 mg CB group. Platelet aggregation was assessed by the VerifyNow assay. The primary outcome was the difference of the percentage P2Y₁₂ inhibition and the secondary outcome was the baseline and change in P2Y₁₂ reaction units (PRU).

Results:

There was no significant difference in the percentage P2Y₁₂ inhibition (CN vs. CB, 34.92 ± 21.33% vs. 30.43 ± 17.90%, p = 0.203). The mean difference of the percentage P2Y₁₂ inhibition between groups was 4.49%, their two-sided 95% confidence interval was −2.45% to 11.44%, and the lower bound (−2.45%) was greater than the acceptable non-inferiority margin of −9.0%. The baseline PRU was 96.67 ± 76.76 in the CN group and 216.95 ± 68.86 in the CB group (p = 0.121), and the change in the PRU was −3.32 ± 51.71 in the CN group and 10.52 ± 43.31 in the CB group (p = 0.106). Four subjects experienced AEs (6.3%, 5 events) in the CN group and 7 subjects (11.11%, 13 events) in the CB group without statistical significance (p = 0.364). With respect to serious adverse events, 2 events were reported in 2 subjects, 1 in each group.

Conclusion:

Clopidogrel napadisilate was not inferior to clopidogrel bisulfate in terms of antiplatelet efficacy and tolerability, and there were no clinically significant adverse events.

Key words: :

• Clopidogrel bisulfate
• Clopidogrel napadisilate
• Efficacy
• P2Y₁₂

Transparency

Declaration of funding

This research was financially sponsored by Hanmi Pharmaceutical Co. Ltd, Seoul, South Korea. The sponsor supported only laboratory testing, study medication, and clinical research coordinator expenses. 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. Hanmi Pharmaceutical also had no input into the decision to submit this article for publication. The authors had full access to all the data in the study, and the corresponding author had the final responsibility to submit the manuscript for publication.

Declaration of financial/other relationships

SH Kim, JH Sung, JH Shin, HJ Lee, HS Lee, DK Cho, and SW Lim have disclosed that they have received sponsorship for the development of this study, but that they have no other 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.

Acknowledgments

Managing support was provided by Mi Jung Jeon and Eun Han Cho of Hanmi Pharm. Co. Ltd, Seoul, South Korea. Editorial assistance was provided by Soung-Youn Ju, Dong-Eun Lee and Jung A Song of CLITRANS, and was funded by Hanmi Pharm. Co. Ltd, Seoul, South Korea.

Notes

*Pidogul is a registered trade name of Hanmi Pharmaceuticals Co. Ltd, Seoul, South Korea

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

*VerifyNow assay is a commercially available kit name of Accumetrics Inc., San Diego, California