Treatment with a single drug that prevents blood clot formation followed by an anticoagulant drug in patients with irregular heartbeat who have undergone coronary blood flow restoration surgery with a stent (MATRIX-2)

Phase 3

Recruiting

• Conditions: AF patients who have undergone successful PCI

• Registration Number: 2023-509717-36-00
• Lead Sponsor: Insel Gruppe AG

Brief Summary

The objectives of this study are to assess the safety, in terms of major or clinically relevant non-major bleeding, and the efficacy in terms of major adverse cardiac and cerebral events of a P2Y12 inhibitor monotherapy regimen for 1 month followed by DOAC monotherapy long-term versus current standard of care consisting of triple antithrombotic therapy for up to one month (aspirin, P2Y12 inhibitor and DOAC) followed by dual antithrombotic therapy (P2Y12 inhibitor and DOAC) for 6 to 12 months and DOAC monotherapy thereafter, in AF patients undergoing PCI indicated for treatment with a DOAC after sirolimus-eluting Supraflex Cruz stent implantation and followed for a period of 15 months.

Detailed Description

Background:

The optimal antithrombotic treatment following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) requiring long-term oral anticoagulation remains a matter of debate. In particular, the appropriate intensity and duration of antithrombotic strategies to prevent ischemic events, while mitigating the risk of bleeding complications in this high bleeding risk population during the early peri-procedural period (within 30 days) and thereafter (from 30 days to 1 year) following drug-eluting stent implantation remains unclear.

Aim:

The investigators aim to assess the safety and efficacy of a P2Y12 inhibitor monotherapy regimen for 1 month followed by DOAC monotherapy long-term versus current standard of care consisting of triple antithrombotic therapy for up to one month (aspirin, P2Y12 inhibitor and DOAC) followed by dual antithrombotic therapy (P2Y12 inhibitor and DOAC) for 6 to 12 months and DOAC monotherapy thereafter, in AF patients undergoing PCI indicated for treatment with a DOAC after sirolimus-eluting Supraflex Cruz stent implantation and followed for a period of 12 months.

Methodology:

This investigator-initiated, multi-center, randomized, open-label, blinded evaluation, international clinical trial in 3010 AF patients with indication for long-term oral anticoagulation who have undergone successful PCI with Supraflex Cruz sirolimus-eluting biodegradable polymer cobalt chromium stent implantation. The study will be conducted at approximately 150 sites across Europe and Brazil. Patients will be randomized to the antithrombotic monotherapy (experimental antithrombotic strategy) or the standard of care strategy (control group) in a 1:1 ratio. Randomization is stratified by site, acute coronary syndrome (ACS) within the previous 6 months and CHA2DS2-VASc score ≥4. Patients randomized to the antithrombotic monotherapy treatment receive any of the commercially available oral P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel) and immediately discontinue aspirin and DOAC. After 1 month, the P2Y12 inhibitor will be stopped and treatment with a commercially available DOAC will be initiated for the duration of 11 months. Patients randomized to the standard of care strategy will initiate triple therapy for up to 1 month followed by dual anti-thrombotic therapy (consisting of P2Y12 inhibitor for a minimum of 6 and up to 12 months plus DOAC for at least 12 months).

Potential significance:

This is the first study investigation the impact of a short course of P2Y12 inhibitor monotherapy up to 1 month, while omitting clopidogrel non-responders, and temporarily omitting OAC, after stent implantation followed by OAC monotherapy in AF patients undergoing PCI. This sequential monotherapy treatment strategy has solid rational and carries potential to balance bleeding against cardiac and cerebral ischemic risks.

Study Timeline

• Study First Posted: 2024-08-13
• Last Update Posted: 2025-02-14

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 1700

Inclusion Criteria

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

Exclusion Criteria

Planned staged percutaneous intervention procedure

Moderate and severe hepatic imparment (Child-Pugh Class B or C) or any hepatic disease associated with coagulopathy

Any hypersensitivity or contraindications for direct oral anticoagulant or dual antiplatelet therapy with aspirin and a P2Y12 inhibitor

Any of the following abnormal local laboratory results prior to randomization: platelet count < 50x10^9/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

Cardioversion for treatment of atrial fibrillation within 1 month prior to inclusion or planned cardioversion

Atrial fibrillation ablation procedure within 2 month prior to inclusion or planed atrial fibrillation ablation procedure

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Major adverse cardiac or cerebral events (MACCE), defined as the composite of death from any cause, myocardial infarction, stroke, or non-CNS systemic embolism between randomization and up to 12 months		Major adverse cardiac or cerebral events (MACCE), defined as the composite of death from any cause, myocardial infarction, stroke, or non-CNS systemic embolism between randomization and up to 12 months
Major or clinically relevant non-major bleeding (MCB) defined according to the International Society of Thrombosis and Hemostasis (ISTH) criteria between randomization and up to 12 months		Major or clinically relevant non-major bleeding (MCB) defined according to the International Society of Thrombosis and Hemostasis (ISTH) criteria between randomization and up to 12 months

Secondary Outcome Measures

Name	Time	Method
Transient ischemic attack		Transient ischemic attack
Hemorrhagic stroke		Hemorrhagic stroke
The individual components of each primary endpoints		The individual components of each primary endpoints
The composite of death from cardiovascular causes, myocardial infarction, or stroke		The composite of death from cardiovascular causes, myocardial infarction, or stroke
The composite of death from cardiovascular causes, myocardial infarction, stroke or non-CNS systemic embolism		The composite of death from cardiovascular causes, myocardial infarction, stroke or non-CNS systemic embolism
Death from cardiovascular or non-cardiovascular causes		Death from cardiovascular or non-cardiovascular causes
The composite of stroke and non-CNS systemic embolism		The composite of stroke and non-CNS systemic embolism
Any stroke (including ischemic, hemorragic, and unknown types)		Any stroke (including ischemic, hemorragic, and unknown types)
Ischemic stroke		Ischemic stroke
The composite of definite or probable stent thrombosis		The composite of definite or probable stent thrombosis
Definite stent thrombosis		Definite stent thrombosis
Hospitalization		Hospitalization
The composite of death or hospitalization		The composite of death or hospitalization
Any target lesion revascularization		Any target lesion revascularization
Any target vessel revascularization		Any target vessel revascularization
Any revascularization		Any revascularization
All bleeding events, also adjudicated according to BARC, TIMI or GUSTO scales		All bleeding events, also adjudicated according to BARC, TIMI or GUSTO scales
Transfusion rates both in patients with and/or without clinically detected overt bleeding		Transfusion rates both in patients with and/or without clinically detected overt bleeding

Trial Locations

Locations (73)

Jessa Ziekenhuis; 🇧🇪 Hasselt, Belgium

Az St-Jan Brugge-Oostende A.V.; 🇧🇪 Brugge, Belgium

CHU de Charleroi Hopital Civil Marie Curie; 🇧🇪 Charleroi, Belgium

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Clinico Universitario De Valladolid; 🇪🇸 Valladolid, Spain

Hospital General Universitario Reina Sofia; 🇪🇸 Cordoba, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital Clinic De Barcelona; 🇪🇸 Barcelona, Spain

Hospital Clinico Universitario De Valencia; 🇪🇸 Valencia, Spain

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Jessa Ziekenhuis

🇧🇪Hasselt, Belgium

Pascal Vranckx

Site contact

+32474891898

pascal.vranckx@jessazh.be