Prasugrel Switching Study in Patients With Acute Coronary Syndrome (ACS) Who Underwent Percutaneous Coronary Intervention (PCI)

Phase IV, Non-comparative, Open Label, Multicenter, 28-Week Switching Study of Prasugrel Maintenance Dose From Clopidogrel in Patients With Acute Coronary Syndrome (ACS) Who Underwent a Percutaneous Coronary Intervention (PCI) in Taiwan

This Phase IV, multicenter trial is designed to assess the efficacy of prasugrel in preventing the formation of blood clots in Taiwanese patients with ACS who have been treated with PCI.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome (ACS)
• Intervention / Treatment: Drug: Prasugrel

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • Mackay Memorial Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Cheng Hsin General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital, Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Is within the age limits and has signed informed consent
• Weighs at least 50 kg

• Had a previous diagnosis of ACS (UA, STEMI, or NSTEMI), underwent PCI, and received one of the following treatments:

  • Clopidogrel MD of 75 mg and aspirin 81-100 mg for 2-8 weeks following clopidogrel loading dose (LD) of 300 mg or 600 mg at the time of PCI
  • Ticagrelor MD of 90 mg twice daily (BID) and aspirin 81-100 mg for 1-4 weeks and switching to clopidogrel MD of 75 mg and aspirin 81-100 mg for 2-4 weeks following ticagrelor LD of 180 mg at the time of PCI
  • Clopidogrel MD 75 mg and aspirin 81-100 mg for 2-8 weeks following ticagrelor LD of 180 mg at the time of PCI
  • Or based on investigator's judgment with at least 2 weeks continued use of clopidogrel MD and aspirin 81-100 mg per day before switching to prasugrel and maximum 8 weeks P2Y12 inhibitors MD treatment (prasugrel is not allowed)
• Is willing and able to abide by the rules of the research unit and study restrictions
• If a woman of child-bearing potential, has a negative serum pregnancy test at screening
• Agrees to use at least one method of contraception during the study

Exclusion Criteria:

• Has active bleeding, significant risk of hemorrhage, or unusual susceptibility to bleed
• Had previous hemorrhagic stroke at any time, or transient ischemic attack (TIA) or ischemic stroke within 3 months before the informed consent date
• Has known allergies or hypersensitivity to prasugrel, aspirin, or any of their excipients
• Has significant hypertension at screening or baseline assessment
• Has hemoglobin levels <10.5 g/dL or hematocrit levels <30%
• Has severe left ventricular systolic dysfunction, ejection fraction <30%
• Is currently undergoing hemodialysis
• Has evidence of severe hepatic disease or any of the following: serum alanine transaminase or aspartate transaminase ≥3 times the upper limit of normal (ULN); or bilirubin ≥2 times the ULN at screening
• Has any clinical laboratory result performed at screening that is determined to be detrimental to the patient or could compromise the study as determined the Investigator
• Has previously participated in this study or in another interventional trial that is not compatible with this study
• Has evidence of significant active neuropsychiatric disease, alcohol abuse or drug abuse as determined by the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel; Participants with ACS who underwent PCI, and were previously taking clopidogrel, receive a maintenance dose (MD) of prasugrel for a total of 28 weeks (optionally up to a maximum 12 months of P2Y12 inhibitor treatment after ACS underwent PCI)	Drug: Prasugrel; Prasugrel, oral tablets, containing 3.75 mg per tablet; Other Names: Efient®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline to Week 4 in P2Y12 Reaction Units During Period 1	The mean change in the P2Y12 reaction unit value assessed from baseline to the end of the 4-week maintenance dose treatment period, after switching from clopidogrel maintenance dose to prasugrel maintenance dose was analyzed with a paired t-test model. Mean changes (including standard deviations) are presented.	Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Number of Participants With Thrombolysis In Myocardial Infarction (TIMI) Major Bleeding Events During Period 2	All safety events were assessed in the overall Safety Population, regardless of the study period. The incidence of major bleeding events (defined as non-coronary artery bypass grafting [CABG] thrombolysis in myocardial infarction (TIMI) major) after 28 maintenance dose treatment weeks (optional maximum 12-month P2Y12 inhibitor treatment after ACS participants underwent PCI) are reported. Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days)	End of Week 4 up to Week 28 post-maintenance dose prasugrel treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With High On-Treatment Platelet Reactivity (HTPR) During Period 1	High On-Treatment Platelet Reactivity (HTPR) was defined as PRU >235.	Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Mean Percentage Change From Baseline to Week 4 in Platelet Inhibition During Period 1	The mean percentage change in platelet inhibition at the end of the 4-week maintenance dose prasugrel treatment period, after switching from clopidogrel maintenance dose to prasugrel maintenance dose is reported.	Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Number of Participants With Adverse Events of Special Interest During Period 1	Adverse events of special interest were defined as major and minor bleeding events, clinically relevant bleeding events, and any major adverse cardiovascular events (MACE). Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days). Non-CABG TIMI minor bleeding was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to less than 5 g/dL.	Baseline up to Week 4 post-maintenance dose prasugrel treatment period
Number of Participants With Adverse Events of Special Interest During Period 2	All safety events were assessed in the overall Safety Population, regardless of the study period. Adverse events of special interest were defined as major and minor bleeding events, clinically relevant bleeding events, and any major adverse cardiovascular events (MACE). Non-CABG TIMI major bleeding was defined as any intracranial bleeding (excluding microhemorrhages less than 10 millimeter evident only on gradient-echo magnetic resonance imaging); clinically overt signs of hemorrhage associated with a drop in hemoglobin of greater than or equal to 5 g/dL; and fatal bleeding (bleeding that directly results in death within 7 days). Non-CABG TIMI minor bleeding was defined as clinically overt (including imaging), resulting in hemoglobin drop of 3 to less than 5 g/dL.	End of Week 4 up to Week 28 post-maintenance dose prasugrel treatment period

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company

Publications and helpful links

General Publications

• Liu PY, Su CH, Kuo FY, Lee WL, Wang YC, Lin WS, Chu PH, Lu TM, Lo PH, Lee CH, Lan WR, Huang CL, Tsukiyama S, Yang WC, Cheng LC, Rafael V, Nikolajsen C, Yin WH. Prasugrel switching from clopidogrel after percutaneous coronary intervention for acute coronary syndrome in Taiwanese patients: an analysis of safety and efficacy. Cardiovasc Interv Ther. 2022 Apr;37(2):269-278. doi: 10.1007/s12928-021-00771-w. Epub 2021 Apr 4. Erratum In: Cardiovasc Interv Ther. 2021 May 22;:

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2018
• Primary Completion (Actual): August 19, 2020
• Study Completion (Actual): August 19, 2020

Study Registration Dates

• First Submitted: September 13, 2018
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (Actual): September 14, 2018

Study Record Updates

• Last Update Posted (Actual): November 12, 2021
• Last Update Submitted That Met QC Criteria: October 15, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Prasugrel; Percutaneous Coronary Intervention (PCI); ST elevation myocardial infarction (STEMI); Non-ST elevation myocardial infarction [NSTEMI]; Unstable angina (UA); ACS-PCI
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride
• Other Study ID Numbers: CS747S-B-A4003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No