Comparison of Reduced Dual Antiplatelet Therapy with Prasugrel Monotherapy Versus Standard Regimen in STEMI Patients Undergoing OCT-Guided Versus Angiography-Guided Revascularization

Trial ID: 2024-515883-30-00
Protocol: RM21
Sponsor: Research Maatschap Cardiologen Rotterdam Zuid

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Diseases & Conditions

Myocardial infarction

Objectives

The primary objective of the study is to demonstrate the non-inferiority of a **Prasugrel**-based short dual antiplatelet therapy (DAPT) regimen, lasting 30-45 days, followed by **Prasugrel** monotherapy, compared to the standard DAPT regimen in patients with ST-Elevated Myocardial Infarction (STEMI). This will be assessed by evaluating the incidence of net adverse clinical events (NACE) 11 months after randomization, which corresponds to 12 months following primary percutaneous coronary intervention (PCI) or the completion of revascularization by staged PCI. The clinical relevance of this objective lies in potentially reducing the duration of DAPT, which may decrease the risk of bleeding complications while maintaining efficacy in preventing thrombotic events.

The co-primary objective is to establish the superiority of Optical Coherence Tomography (OCT)-guided revascularization completion over standard angiography-guided revascularization in patients with multivessel disease. This will be measured in terms of post-procedural Minimal Stent Area (MSA), which is crucial for ensuring optimal stent deployment and reducing the risk of restenosis.

Participants

The clinical trial involves participants diagnosed with **ST-Elevated Myocardial Infarction** (STEMI). The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically encompass adults and older adults. The participants are not from a vulnerable population. The sponsor has not provided the total number of participants. The trial population was selected based on specific eligibility criteria, including patients who have undergone percutaneous coronary intervention (PCI) and are compliant with dual antiplatelet therapy (DAPT) without regimen modifications. Participants are required to have no significant events such as myocardial infarction, unplanned revascularization, or major bleeding complications within the specified period. Lifestyle considerations such as diet and physical activity are not detailed in the provided data.

Plans and Procedures

The clinical trial is designed to evaluate the efficacy and safety of a **prasugrel**-based short dual antiplatelet therapy (DAPT) followed by **prasugrel** monotherapy compared to a standard DAPT regimen in patients with **ST-Elevated Myocardial Infarction** (STEMI). The trial employs a randomized, double-blind, controlled design to ensure unbiased results. The study aims to demonstrate the non-inferiority of the **prasugrel** regimen by assessing the incidence of Net Adverse Clinical Events (NACE) 11 months post-randomization. Additionally, the trial seeks to establish the superiority of Optical Coherence Tomography (OCT)-guided revascularization over angiography-guided methods in terms of post-procedural Minimal Stent Area (MSA).

The trial is expected to span from July 2022 to July 2028, with participant involvement lasting up to 35 months. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by randomization and subsequent follow-up visits at 2, 11, and 35 months. The end-of-study visit will occur at the conclusion of the participant's involvement. Participants will be monitored for adherence to the treatment regimen and any significant adverse events, such as myocardial infarction, unplanned revascularization, or major bleeding, which may lead to early termination from the study.

Inclusion criteria require participants to be STEMI patients planned for percutaneous coronary intervention (PCI), with specific electrocardiogram (ECG) features and successful revascularization. Exclusion criteria are not explicitly detailed in the provided data. The primary endpoints include the composite of cardiovascular deaths, myocardial infarction, stroke, or bleeding at 11 months, and the post-procedural MSA assessed by OCT. Secondary endpoints involve Major Adverse Cerebrovascular Events (MACE) and other procedural outcomes assessed at various intervals throughout the study.

Treatment

The clinical trial involves the administration of **Acetylsalicylic Acid**, a chemical compound, as an experimental medication. This medication is provided in the form of a hard capsule and is administered orally. The maximum daily dose is 100 mg, with a total maximum dose of 100 mg. The treatment period for this medication is up to 36 months. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

Another experimental medication used in the trial is **Prasugrel**, also a chemical compound. Prasugrel is administered in the form of a film-coated tablet, taken orally. The maximum daily dose is 10 mg, with a total maximum dose of 10 mg. The treatment period for Prasugrel is up to 12 months. As with Acetylsalicylic Acid, participant compliance with the dosing schedule is closely monitored to maintain the integrity of the trial data.

In addition to the experimental medications, the trial may involve the use of standard-of-care therapies as comparator treatments. These therapies are not specified in the provided data but are typically used to establish a baseline for evaluating the efficacy and safety of the experimental treatments. The trial's objective is to assess the non-inferiority of a Prasugrel-based short dual antiplatelet therapy (DAPT) followed by Prasugrel monotherapy compared to a standard DAPT regimen, with a focus on the incidence of net adverse clinical events (NACE) and the superiority of Optical Coherence Tomography (OCT)-guided revascularization in patients with multivessel disease.

Efficacy

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the incidence of **Net Adverse Clinical Events (NACE)**, which is a composite endpoint encompassing cardiovascular deaths, myocardial infarction, stroke, or bleeding classified as BARC type 3 or 5, evaluated at 11 months post-DAPT randomization. Additionally, the post-procedural Minimal Stent Area (MSA) will be assessed using Optical Coherence Tomography (OCT) in each randomized arm, with measurements conducted at an independent OCT core laboratory blinded to the imaging modality assignment.

Secondary endpoints will further evaluate efficacy by measuring Major Adverse Cerebrovascular Events (MACE), which include deaths, myocardial infarction, or stroke at 2, 11, and 35 months. The incidence of BARC type 3 or 5 bleeding events will also be assessed at these timepoints. Other secondary endpoints include the incidence of target vessel failure (TVF), defined as the composite time-to-first event rate of death, target vessel myocardial infarction (TV-MI), or ischemia-driven target vessel revascularization (ID-TVR) at 2, 11, and 35 months. Procedural outcomes will be evaluated through OCT-defined parameters such as stent expansion, edge dissection, and stent malapposition, with assessments conducted per target lesion. The incidence of stent thrombosis, classified as definite or probable, will also be monitored.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Eligibility at index procedure All STEMI patients who are planned to be treated with PCI: ST segment elevation myocardial infarction Chest discomfort suggestive of cardiac ischemia ≥20 min at rest with 1 of the following ECG features:  ST segment elevation ≥2 contiguous ECG leads  new or presumably new left bundle branch block In patients with multivessel disease, treatment only of the culprit lesion / target vessel during primary PCI is recommended.
Eligibility at 30-45 days  All patients who have provided informed consent Compliance to DAPT with no regimen modifications (Non-adherence Academic Research Consortium 0; see section 6.4.4)  No occurrence of significant event (such as MI, unplanned revascularisation, stent thrombosis, stroke, major vascular complication/bleeding BARC Types 3 or greater).  Successful revascularization: - Successful delivery and deployment of the Study device(s), with final residual stenosis of <30% (visually) for all target lesions.  Complete revascularization performed when more than 1 significant lesion, in staged procedure(s) occurring within 15 days from the index procedure. Physiologic assessment highly recommended for lesions with stenosis between 50% and 90%.

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Exclusion Criteria

Patients on oral anticoagulation - Contraindication to P2Y12 inhibitors and/or to Cardioaspirin or to any of the excipients (hypersensitivity, history of any stroke or transient ischemic attack within the last 12 months, active bleeding or haemorrhagic diathesis, fibrin-specific fibrinolytic therapy less than 24 h before randomization, severe hepatic dysfunction (Child-Pugh C), history of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines, history of gastrointestinal perforation or acute gastrointestinal ulcers, severe cardiac failure (NYHA grade III or IV), combination with methotrexate at doses of 15 mg/week or more). - Patients who have received P2Y12 inhibitors other than Prasugrel in the ambulance (Ticagrelor or Clopidogrel loading dose) or are already on P2Y12 inhibitors, may be enrolled in the protocol, provided that the Prasugrel loading dose is administered at admission, according to current guidelines recommendations (see section 5.2.2). - Concomitant oral or i.v. therapy with strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, grapefruit juice >1L/day), CYP3A substrates with narrow therapeutic indices (e.g., cyclosporine, quinidine), or strong CYP3A inducers (e.g., rifampin) - rifampicin, phenytoin, carbamazepine, dexamethason, phenobarbital - Platelet count <100.000/μL at the time of screening - Anemia (hemoglobin <10 g/dL) at the time of screening - Comorbidities associated with life expectancy <1 year - Pregnancy, giving birth within the last 90 days, or lactation (see appendix III for women of childbearing potential) - PCI indication for stent thrombosis or previous history of definite stent thrombosis - Non-deferrable major surgery on DAPT after PCI - Cardiogenic shock - Out of hospital cardiac arrest (OHCA) unless survivors of ventricular arrythmia with prompt return of spontaneous circulation (ROSC) - Patients with severe renal impairment: creatinine clearance ≤30 ml/min/1.73 m2 (as calculated by MDRD formula for estimated GFR). - Patients participating in another interventional (device of drug trial) within the previous 12 months or patients to whom an investigational drug was administered in the 30 days prior to screening, or 5 half-lives of the study drug, whichever is longer. - No informed consent

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Recruiting	20 Jul 2022	300
Czechia	Recruiting	20 Jul 2022	100
Germany	Recruiting	20 Jul 2022	100
Italy	Recruiting	20 Jul 2022	400
The Netherlands	Recruiting	20 Jul 2022	—
Netherlands	—	—	700