Tailored Versus Conventional AntiPlaTelet Strategy Intended After OPTIMIZEd Drug Eluting Stent (OPTIMIZE-APT)

Asan Medical Center

Status and phase: Enrolling; Phase 4

Conditions: Coronary Artery Disease

Treatments: Drug: aspirin

Study type: Interventional

Funder types: Other

Identifiers

NCT05418556

2022-0568

Details and patient eligibility

About

Objectives: To assess the safety of tailored antiplatelet therapy (short DAPT followed by P2Y12 inhibitor alone strategy) in patients who received optimized DES implantation guided by intravascular imaging (IVUS or OCT)

Hypothesis: Tailored antiplatelet strategy (short DAPT followed by P2Y12 inhibitor alone) is superior to conventional antiplatelet strategy in terms of clinically relevant bleeding and noninferior for ischemic composite adverse events in patients who received intravascular imaging-guided optimized DES implantation. (Optimized stent evaluated by on-site IVUS/OCT could act as an essential criterion for decision making for tailored antithrombotic strategy)

Full description

Objective: To assess the safety of tailored antiplatelet strategy (short DAPT followed by P2Y12 inhibitor alone) in patients who received optimized DES implantation guided by intravascular imaging (IVUS or OCT)

Design: Prospective, open label, multi-center, dual arm, randomized trial Number of Subjects 3,944 subjects (1972:1972) Study Population: Patients with coronary artery disease undergoing imaging-guided PCI

Study Design:

• Eligible subjects will be randomized 1:1 to a) conventional DAPT strategy or b) tailored anti-platelet strategy (short DAPT followed by P2Y12 inhibitor alone) after optimized DES implantation guided by intravascular imaging.
• All subjects will be clinically followed at 1(or 3), 6, and 12, 18, 24, 36, 48, 50 months

Co-primary Endpoints:

1. Ischemic composite of all-cause death, myocardial infarction, ischemia-driven target-vessel revascularization, and definite or probable stent thrombosis at 12 months post-PCI
2. Net adverse clinical events, defined as the ischemic composite plus clinically relevant bleeding at 12 months post-PCI
3. Clinically relevant bleeding, defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 12 months post-PCI

Statistics and Analysis: The study was designed to test the hypothesis that tailored antithrombotic strategy, as compared to the conventional DAPT, would be superior for clinically relevant bleeding, noninferior to the ischemic composite adverse events and NACE. The primary analysis would be evaluated by intention-to-treat analysis. With 3756 (each 1,878) patients, this study has >80% power to detect noninferiority of tailored antiplatelet strategy for ischemic composite adverse event, >85% power to detect noninferiority of tailored antiplatelet strategy for NACE, and >85% power to detect superiority of the tailored antiplatelet arm on clinically relevant bleeding. To compensate for 5% attrition rate, 3,944 (each 1,972) patients will be randomized.

Enrollment: 3,944 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Men or women ≥19 years

2. Typical chest pain or objective evidence of myocardial ischemia suitable for PCI

3. Significant de novo coronary artery lesions suitable for DES implantation

4. Patients who underwent optimized stent implantation either by IVUS or OCT

   • Using IVUS

     • MSA >5.5 mm2, or MSA >90% of the MLA at the distal reference segment
     • Plaque burden <50% with 5 mm of both stent edge
     • No edge dissection; thrombus or plaque protrusion occupying < 10% of the stent area

   • Using OCT

     • MSA >4.5 mm2, or MSA >90% of the MLA at the distal reference segment
     • No significant malapposition
     • No significant edge dissection†; thrombus or plaque protrusion occupying < 10% of the stent area

   (*Significant malapposition is defined as strut separation ≥ 0.3 mm from the vessel wall extending over a length > 3 mm.

   †Significant dissection is defined as a dissection penetrating the medial layer and extending over more than one quadrant.)

5. The patient or guardian agrees to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site

Exclusion criteria

1. Angiographic exclusion criteria: any of the followings 1. Bypass graft lesions 2. Lesions in which impaired delivery of imaging catheters is expected:

   • Extreme angulation (≥90°) proximal to or within the target lesion.
   • Excessive tortuosity (≥ two 45° angles) proximal to or within the target lesion.
   • Heavy calcification proximal to or within the target lesion.

2. In-stent restenosis

3. Hypersensitivity or contraindication to device material and its degradants and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers that cannot be adequately pre-medicated.

4. Persistent thrombocytopenia (platelet count <80,000/μl)

5. Any history of hemorrhagic stroke or intracranial hemorrhage / TIA or ischemic stroke within the past 6 months

6. A known intolerance or hypersensitivity to a study drug (aspirin, clopidogrel or ticagrelor) or heparin

7. Patients requiring long-term oral anticoagulants or cilostazol

8. Any surgery requiring general anesthesia or discontinuation of aspirin and/or an ADP antagonist is planned within 12 months after the procedure.

9. A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer.

10. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.

11. History of liver cirrhosis (Child-Pugh B or C) or biliary tract obstruction

12. Life expectancy < 1 years for any non-cardiac or cardiac causes

13. Cardiogenic shock at the index admission

14. Patient's pregnant or breast-feeding

15. Active bleeding or extreme-risk for major bleeding (e.g. active peptic ulcer disease, gastrointestinal pathology with a high risk for bleeding, malignancies with a high risk for bleeding)

16. Unwillingness or inability to comply with the procedures described in this protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,944 participants in 2 patient groups

Conventional Arm

Active Comparator group

Description:

The antiplatelet regimens Post-PCI are at least 6-month DAPT (aspirin plus clopidogrel) for CCS, and at least-12month DAPT (aspirin plus P2Y12 inhibitor \[Ticagrelor, prasugrel\]) for ACS.

Treatment:

Drug: aspirin

Tailored Arm

Experimental group

Description:

The antiplatelet regimens post-PCI are 1-month DAPT (aspirin plus clopidogrel) followed by 11-months clopidogrel alone for CCS, and 3-months DAPT (aspirin plus P2Y12 inhibitor \[ticagrelor, prasugrel\]) followed by 9-months P2Y12 inhibitor alone for ACS.

Treatment:

Drug: aspirin