Monotherapy With P2Y12 Inhibitors in Patients With Atrial fIbrillation Undergoing Supraflex Stent Implantation

NCT05955365 | Recruiting Phase 4 DMC

• 1 other identifier: MATRIX-2
• Study Type: interventional
• Target: 3,010
• Locations: 9 countries
• Sites: 15

Brief Summary

Patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation require treatment with different antithrombotic drugs. Oral anticoagulants are prescribed to reduce the risk of stroke associated with atrial fibrillation. Antiplatelet substances are prescribed after stent implantation to reduce the risk of adverse cardiac events such as myocardial infarction or stent thrombosis. Treatment with antithrombotic medications can cause bleeding complications, particularly when these substances are combined. The currently recommended standard strategy consists of treatment with 3 antithrombotic medications for at least 1 week up to one month, followed by treatment with two of these medications for up to 6-12 months after stent implantation. Thereafter, patients usually receive long-term treatment with only one drug, an anticoagulant. In the monotherapy group of this study, the investigators will investigate a strategy where only one antithrombotic drug will be used at a time. During the first month after stent implantation, the investigators will prescribe an antiplatelet medication, followed by an oral anticoagulant as monotherapy. This strategy might be associated with fewer bleeding complications, while protecting adequately against thrombotic events. In this study the investigators would like to investigate whether treatment with a single antithrombotic drug ("monotherapy strategy") is associated with benefits compared to the currently recommended combination therapy of antithrombotic medications ("standard-of-care strategy").

Conditions

Percutaneous Coronary Intervention (PCI); Atrial Fibrillation (AF); Oral Anticoagulation; P2Y12 Inhibitor

Outcome Measures

Primary Outcomes (2)

• The number of participants with a major adverse cardiac or cerebral events (MACCE), defined as the composite of death from any cause, myocardial infarction, stroke or non-central nervous system (non-CNS) systemic embolism

  12 months

• The number of participants with a major or clinically relevant non-major bleeding (MCB), defined according to the International Society of Thrombosis and Haemostasis (ISTH) criteria

  12 months

Secondary Outcomes (37)

• The incidence of MACCE or MCB

  12 months

• The incidence of MACCE or MCB

  15 months

• The number of participants with a composite of death from cardiovascular causes, myocardial infarction or stroke

  12 months

• The number of participants with a composite of death from cardiovascular causes, myocardial infarction or stroke

  15 months

• The number of participants with a composite of death from cardiovascular causes, myocardial infarction, stroke or non-CNS systemic embolism

  12 months

Study Arms (2)

Monotherapy strategy

EXPERIMENTAL

Patients randomized to the monotherapy treatment arm receive any of the commercially available oral P2Y12 inhibitors (clopidogrel, prasugrel oder ticagrelor) and immediately discontinue aspirin and DOAC (or will not re-start DOAC after PCI if treatment was temporarily stopped before). After 1 month, the P2Y12 inhibitor will be stopped and treatment with a commercially available DOAC (at investigator's discretion and dosed according to the instructions for use in patients with atrial fibrillation) will be initiated for the duration of 11 months. After completion of the 12-month study regimen (study visit), the patient will receive antithrombotic therapy according to routine care.

Drug: P2Y12 inhibitor; Drug: DOAC

Standard of care strategy

ACTIVE COMPARATOR

Patients randomized to the standard of care, receive DOAC for at least 12 months. In addition, aspirin is administered for up to 1 month after PCI at investigator's discretion and one of the available P2Y12 inhibitors (clopidogrel, prasugrel oder ticagrelor at investigator's discretion) is administered for a minimum of 6 months and up to 12 months after PCI. After completion of the 12-month control arm regimen (study visit), the patients will be treated according to routine care.

Drug: P2Y12 inhibitor; Drug: Aspirin; Drug: DOAC

Interventions

P2Y12 inhibitor DRUG

The choice of P2Y12 inhibitor is left at investigator's discretion.

Monotherapy strategy; Standard of care strategy

Aspirin DRUG

Aspirin is administered for up to 1 month after PCI at investigator's discretion

Standard of care strategy

DOAC DRUG

The choice of DOAC is left at investigator's discretion.

Monotherapy strategy; Standard of care strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Atrial fibrillation or flutter with an indication for oral anticoagulation using direct-acting oral anticoagulants (DOACs) for ≥12 months
• Successful percutaneous coronary intervention in at least 1 lesion within the previous 7 days with no remaining lesions intended for treatment.
• Free from major adverse events post qualifying PCI, including new onset chest pain suspected to be of ischemic origin, acute or subacute stent thrombosis, new-onset neurological signs or symptoms.
• Written informed consent

You may not qualify if:

• Planned staged percutaneous intervention procedure (Patients can be enrolled after complete coronary revascularization with no remaining lesions intended for treatment. Patients who have or develop indication to percutaneous valve intervention can undergo treatment more than 30 days after qualifying PCI.)
• Prior mechanical valvular prosthesis implantation
• Deep vein thrombosis/pulmonary embolism, at least moderately severe mitral stenosis or other clinical conditions than atrial fibrillation requiring long-term oral anticoagulation
• Stroke within 1 month prior to randomization
• Hemodynamic instability (persistent systolic blood pressure below 90 mmHg, continuous infusions of catecholamines, clinical signs of hypoperfusion and/or use of percutaneous left ventricular assist devices)
• Uncontrolled severe hypertension with a systolic blood pressure (BP) ≥180 mmHg and/or diastolic BP ≥120 mmHg
• Severe renal impairment with estimated creatinine clearance (CrCL) \<15 mL/min or on dialysis
• Moderate or severe hepatic impairment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy
• Any hypersensitivity or contraindications for direct oral anticoagulation or dual antiplatelet therapy with aspirin and a P2Y12 inhibitor
• Any of the following abnormal local laboratory results prior to randomization: platelet count \<50 x109/L or hemoglobin \<8 g/dL
• Known pregnancy or breast-feeding patients
• Life expectancy \<1 year due to other severe non-cardiac disease
• Planned surgery including coronary artery bypass grafting within the next 6 months

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Sahajanand Medical Technologies Limited: collaborator

Study Sites (15)

Hartcentrum Hasselt

Hasselt, 3500, Belgium

NOT YET RECRUITING

CHU Nîmes

Nîmes, 30029, France

NOT YET RECRUITING

Universitätsklinikum Frankfurt/Main

Frankfurt am Main, 60590, Germany

NOT YET RECRUITING

Klinikum Friedrichshafen

Friedrichshafen, 88048, Germany

NOT YET RECRUITING

Ospedale Ferrarotto

Catania, Catania CT, 95124, Italy

NOT YET RECRUITING

IRCCS Humanitas

Milan, Rozzano, 20089, Italy

NOT YET RECRUITING

UMC public

Amsterdam, 1081, Netherlands

NOT YET RECRUITING

Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu

Poznan, 61-701, Poland

NOT YET RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

NOT YET RECRUITING

Cardiocentro Ticino Institute

Lugano, Canton Ticino, 6900, Switzerland

RECRUITING

Universitätsspital Basel

Basel, 4031, Switzerland

RECRUITING

Inselspital, Bern University Hospital, Department of Cardiology

Bern, 3010, Switzerland

RECRUITING

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

RECRUITING

University Hospital Zürich

Zurich, 8091, Switzerland

RECRUITING

Imperial College London

London, SW7 2AZ, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Stephan Windecker, Prof

  Bern University Hospital, Department of Cardiology

  PRINCIPAL INVESTIGATOR

• Marco Valgimigli, Prof

  Cardiocentro Ticino Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephan Windecker, Prof.

CONTACT

+41 31 632 44 97; Stephan.Windecker@insel.ch

Marco Valgimigli, Prof

CONTACT

+41 91 805 31 11; Marco.Valgimigli@eoc.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 21, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); NL (1); CH (5); PL (1); ES (1); IT (2); GB (1); FR (1); BE (1)