Comparison Of Reduced DAPT Followed by P2Y12 Inhibitor Monotherapy With Prasugrel vs stAndard Regimen in STEMI Patients

COMPARE STEMI ONE- Comparison Of Reduced DAPT Followed by P2Y12 Inhibitor Monotherapy With Prasugrel vs stAndard Regimen in STEMI Patients Treated With OCT-guided vs aNgio-guided completE Revascularization

The study is a multi-centre, Open-label, Randomized Controlled, 1:1 trial comparing Prasugrel-based short DAPT (30-45 days) followed by Prasugrel monotherapy versus standard DAPT regimen in STEMI patients in terms of safety and efficacy endpoints.

In the subgroup of STEMI patients with MVD, a sub-randomization will allow a comparison between a complete revascularization OCT-guided versus complete revascularization angiography-guided stent in terms of efficacy and safety endpoints.

Study Overview

• Status: Recruiting
• Conditions: ST Elevated Myocardial Infarction; Dual Antiplatelet Therapy
• Intervention / Treatment: Drug: Prasugrel based short DAPT; Drug: Prasugrel based standard DAPT; Device: OCT guided revascularization; Device: Angio guided revascularization

Detailed Description

Consecutive patients with STEMI planned for pPCI will be screened for eligibility criteria and treated as per standard of care with ASA and Prasugrel 60 mg loading dose. The culprit lesion will be treated during the index procedure. Non culprit lesions in patients with MVD will be treated during staged procedure(s), in any case last instalment of staged procedure(s) should be scheduled within 15 days after index procedure. Complete revascularization of non culprit lesions will be allocated to either OCT- or angio-guided strategy (OCT randomization). At 30-45 days follow-up after index procedure, if inclusion criteria are met, patients will be randomized to prasugrel monotherapy or standard DAPT regimen (DAPT randomization).

The follow-up duration is 35 months after DAPT randomization, i.e. clinical outcomes will be analysed at 11 and 35 months after DAPT randomization.

• Study Type: Interventional
• Enrollment (Estimated): 1608
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Valeria Paradies, MD; Phone Number: +31621620153; Email: paradiesV2@maasstadziekenhuis.nl
• Study Contact Backup: Name: Ria van Vliet; Phone Number: +31644162844; Email: vlietM@maasstadziekenhuis.nl

Study Locations

• Germany
  • Bad Segeberg, Germany
    • Recruiting
    • Segeberger Kliniken
    • Contact: Gert Richardt, PhD
    • Principal Investigator: Gert Richardt, PhD
  • Dresden, Germany
    • Not yet recruiting
    • University Hospital Dresden
    • Principal Investigator: Axel Linke
    • Contact: Axel Linke, PhD
• Italy
  • Ferrara, Italy
    • Recruiting
    • University of Ferrara
    • Contact: Gianluca Campo, PhD
    • Principal Investigator: Gianluca Campo, PhD
  • Genova, Italy
    • Recruiting
    • University San Martino
    • Contact: I. Porto, PhD
    • Principal Investigator: I. Porto, PhD
  • Napoli, Italy
    • Recruiting
    • University Federico II
    • Contact: G. Esposito, PhD
    • Principal Investigator: G. Esposito, PhD
  • Roma, Italy
    • Recruiting
    • University Gemelli
    • Contact: F. Burzotta, PhD
    • Principal Investigator: F. Burzotta, PhD
• Netherlands
  • Dordrecht, Netherlands
    • Recruiting
    • Albert Schweitzer Ziekenhuis
    • Principal Investigator: Rohit Oemrawsingh
    • Contact: Rohit Oemrawsingh, PhD
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus Medical Center
    • Contact: Nicolas van Mieghem, PHD
    • Principal Investigator: Nicolas v Mieghem
  • Rotterdam, Netherlands
    • Recruiting
    • Maasstadziekenhuis
    • Principal Investigator: Valeria Paradies
    • Contact: Valeria Paradies; Phone Number: +31621620153; Email: paradiesV2@maasstadziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)
• 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, during the index procedure or in staged procedure(s) occurring within 15 days from the index procedure. Physiologic assessment highly recommended for lesions with stenosis between 50% and 90%.

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel-based short DAPT; Prasugrel-based short DAPT (30-45 days) followed by Prasugrel monotherapy for 11 months.	Drug: Prasugrel based short DAPT; Prasugrel-based short DAPT (30-45 days) followed by Prasugrel monotherapy versus
Active Comparator: Prasugrel based standard DAPT; Prasugrel-based DAPT for 1 year	Drug: Prasugrel based standard DAPT; Prasugrel based DAPT for 1 year
Experimental: OCT guided non-culprit lesion; Complete revascularization of non culprit lesions guided by OCT	Device: OCT guided revascularization; OCT guided revascularization of the non-culprit lesions
Active Comparator: Angio guided non-culprit lesion; Complete revascularization of non culprit lesions guided by Angio	Device: Angio guided revascularization; Angio guided revascularization of the non-culprit lesions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
non inferiority of a Prasugrel-based short DAPT (30-45 days) followed by Prasugrel 11 month monotherapy versus standard 12 month DAPT regimen	Incidence of Net Adverse Clinical Events (NACE) at 11 months post DAPT randomization as composite of all cause death, MI, stroke or BARC bleeding 3 or 5	11 months
superiority of an Optical Coherence Tomography (OCT)-guided revascularization completion as compared to a standard angiography-guided revascularization completion.	Post-procedural Minimal Stent Area (MSA)	immediately after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of MACCE	Composite of the number of major adverse cardiac and cerebrovascular events (MACCE) defined as cardiovascular death, myocardial infarction, or ischaemic stroke	3 year
BARC type 3 or 5 events	Number of BARC type 3 or 5 events occuring	1 and 3 years

Collaborators and Investigators

• Sponsor: Research Maatschap Cardiologen Rotterdam Zuid
• Collaborators: Abbott Medical Devices
• Investigators: Principal Investigator: Valeria Paradies, MD, PhD, Research Maatschap Cardiologen Rotterdam Zuid

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2022
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride
• Other Study ID Numbers: RM21

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