Comparison of Dual Antiplatelet Therapy De-escalation by Dose Reduction Versus Switching in Patients Undergoing PCI: The Switching Antiplatelet-8 (SWAP-8) Study (SWAP-8)

May 8, 2026 updated by: University of Florida

Comparison of Dual Antiplatelet Therapy De-escalation by Dose Reduction Versus Switching in Patients Undergoing PCI: A Prospective, Randomized Pharmacodynamic Study - The Switching Antiplatelet-8 (SWAP-8) Study

Dual antiplatelet therapy (DAPT) with low-dose aspirin and a P2Y12 inhibitor is the current standard of care in patients with coronary artery disease experiencing an acute event or undergoing percutaneous coronary intervention. However, the ischemic benefits are counterbalanced by a significant increase in bleeding events. Over time, different DAPT de-escalation strategies have been developed to reduce the bleeding risk while maintaining the ischemic protection, but there is currently no head-to-head comparison between them. The purpose of this clinical trial is to conduct a head-to-head comparison on the pharmacodynamic efficacy of DAPT de-escalation by dose reduction to low-dose prasugrel (5 mg od) and DAPT de-escation by switching from standard-dose more potent P2Y12 receptor inhibitor to standard-dose clopidogrel (75 mg). To determine if the PD profiles of these two strategies are comparable, we aim to conduct a non-inferiority study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The combination of low-dose aspirin and a P2Y12 receptor inhibitor, commonly referred as dual antiplatelet therapy (DAPT), is guideline-recommended for preventing atherothrombotic events in patients experiencing an acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). In ACS patients undergoing PCI, DAPT is initiated at the time of the event and maintained for up to one year to mitigate the risks of stent-related complications and ischemic recurrences.4 There are 3 currently available oral P2Y12 inhibitors: clopidogrel, prasugrel, and ticagrelor. Among ACS patients undergoing PCI, prasugrel and ticagrelor are recommended over clopidogrel because of their enhanced efficacy in reducing ischemic events, including stent thrombosis. However, the increased antiplatelet potency of prasugrel and ticagrelor enhances the risk of bleeding, which has detrimental effects on the overall patient prognosis. The increased risk of mortality in patients experiencing bleeding events underscores the need for antiplatelet strategies that reduce bleeding risk while maintaining significant ischemic protection.

The majority of recurrent ischemic events, including stent thrombosis, tend to occur within the first 1 to 3 months after the index PCI procedure. As a result, in clinical practice it is common to use more potent antiplatelet therapies during the early (i.e., 1-3) months post-PCI, when platelet reactivity is heightened, and transition to therapies with lower platelet inhibition thereafter. This strategy, aimed at reducing bleeding risks while providing ischemic protections, is referred to as de-escalation and its implementation is supported by practice guidelines. In line with Academic Research Consortium (ARC) definitions, de-escalation can be implemented in 3 ways: a) by switching from a more potent to a less potent P2Y12 inhibitor; b) by dose reduction (e.g., lowering prasugrel or ticagrelor doses as an alternative to the initial regimen) or c) by stopping one antiplatelet drug (e.g., either the P2Y12 inhibitor or aspirin). Of the available de-escalation strategies, two of these allow patients to remain on a DAPT regimen maintaining the synergistic effect of targeting two different platelet activation pathways: de-escalation by switch and de-escalation by dose reduction. Notably, pharmacodynamic (PD) response to clopidogrel is characterized by a significant interindividual variability, which is partially mediated by specific alleles encoding the cytochrome P450 2C19. Thus, carriers of these alleles may be at increased risk of thrombotic events if a DAPT de-escalation by switch to clopdogrel is pursued.

In contrast, de-escalation by dose reduction has limited supporting evidence and low adoption in clinical practice. With a de-escalation by dose reduction strategy, patients remain on a potent P2Y12 inhibitor (i.e., prasugrel or ticagrelor) but at lower doses, which can reduce side effects, such as bleeding, without compromising efficacy, as these drugs have a more predictable PD response compared to clopidogrel. To date, clinical trial data on dose reduction after the early acute phase (i.e., 1-3 months) in patients with ACS undergoing PCI is limited and shown only with prasugrel. Notably, a recent head-to-head randomized controlled trial favoring prasugrel over ticagrelor, along with the availability of generic formulations of prasugrel, has led to a shift in antiplatelet prescriptions toward prasugrel. However, although there is extensive evidence comparing various de-escalation strategies with standard-of-care DAPT regimens, there are very few studies directly comparing de-escalation strategies with each other, setting the rationale for this investigation. To determine if the pharmcodynamic profiles of DAPT de-escalation by dose-reduction and by switching to clopidogrel are comparable, we aim to conduct a non-inferiority study.

Study Type

Interventional

Enrollment (Estimated)

78

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Recruiting
        • University of Florida
        • Contact:
        • Contact:
        • Principal Investigator:
          • Luis Ortega, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patients who have undergone PCI and are on maintenance treatment with DAPT, consisting of low-dose aspirin with either prasugrel (10 mg qd) or ticagrelor (90 mg bid) as part of standard of care. In particular, patients who underwent PCI in the setting of an acute coronary syndrome will be eligible for randomization after ≥90 days post-PCI, while patients who underwent PCI in the setting of a chronic coronary syndrome ≥30 days post-PCI.
  2. Age ≥18 years.
  3. Provide written informed consent.

Exclusion Criteria:

  1. Prior history of stent thrombosis
  2. Prior cerebrovascular event
  3. PCI within 30 days
  4. Predicted poor metabolizer of clopidogrel based on CYP2C19 genotyping (e.g., *2/*2 or *3/*3),
  5. On treatment with any oral anticoagulant (vitamin K antagonists, dabigatran, rivaroxaban, apixaban, edoxaban) or chronic low-molecular-weight heparin (at venous thrombosis treatment, not for prophylaxis)
  6. Hemodynamic instability
  7. Hypersensitivity to Aspirin, Clopidogrel, or Prasugrel
  8. Known hematologic malignancies or thrombocytopenia (platelet count <80x106/mL)
  9. Known hemoglobinopathies or anemia (hemoglobin <9 g/dL)
  10. Pregnant and breastfeeding women [women of childbearing age must use reliable birth control (i.e., oral contraceptives) while participating in the study].

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: DAPT de-escalation by switch
Drug: clopidogrel 75 mg
Clopidogrel 75 mg od for 30 ± 5 days
Experimental: DAPT de-escalation by dose-reduction
Drug: Prasugrel 5 mg
Prasugrel 5 mg od for 30 ± 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet reactivity measured by VerifyNow
Time Frame: 30±5 days
The primary endpoint of the study will be to establish non-inferiority by comparing PRU levels, determined using the VerifyNow system, between de-escalation through dose reduction to low-dose prasugrel (5 mg qd) and de-escalation through switching to standard-dose clopidogrel (75 mg qd) at trough levels.
30±5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet reactivity measured by VerifyNow
Time Frame: 30±5 days
If non-inferiority is established, a superiority analysis will be conducted by comparing PRU levels, determined using the VerifyNow system, between de-escalation through dose reduction to low-dose prasugrel (5 mg qd) and de-escalation through switching to standard-dose clopidogrel (75 mg qd) at trough levels.
30±5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2025

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

January 7, 2027

Study Registration Dates

First Submitted

February 6, 2025

First Submitted That Met QC Criteria

February 6, 2025

First Posted (Actual)

February 11, 2025

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB202401735

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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