Monotherapy with a P2Y12 inhibitor followed by a direct-acting oral anticoagulant in patients with ATRial fIbrillation undergoing suprafleX Cruz coronary stent implantation (MATRIX-2)
Overview
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Insel Gruppe AG
- Enrollment
- 1,700
- Locations
- 73
- Primary Endpoint
- 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
Overview
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Primary Purpose
- 15 Months Experimental Period
- Masking
- None
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
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 Outcomes
- Transient ischemic attack
- Hemorrhagic stroke
- 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, stroke or non-CNS systemic embolism
- Death from cardiovascular or non-cardiovascular causes
- The composite of stroke and non-CNS systemic embolism
- Any stroke (including ischemic, hemorragic, and unknown types)
- Ischemic stroke
- The composite of definite or probable stent thrombosis
- Definite stent thrombosis
- Hospitalization
- The composite of death or hospitalization
- Any target lesion revascularization
- Any target vessel revascularization
- Any revascularization
- 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
Investigators
Phidealive srl
Scientific
Insel Gruppe AG