Zotarolimus vs Sirolimus Eluting Stent in High Bleeding Risk

Study Overview
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Brief Summary
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Randomized, single-blind, single-center, non-inferiority clinical trial to compare target lesion failure (TLF) at 12 months in high bleeding risk patients who underwent elective coronary percutaneous intervention with a zotarolimus eluting stent versus a sirolimus eluting stent and short Dual Antiplatelet Therapy (DAPT).

Official Title
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Zotarolimus Eluting Stent Versus Sirolimus Eluting Stent in High Bleeding Risk Angioplasty

Conditions
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High Bleeding Risk, Coronary Artery Disease, Percutaneous Coronary Intervention

Intervention / Treatment
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* Device: Zotarolimus eluting stent
* Device: Sirolimus eluting stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years old or older with an ischemic de-novo lesion(s) in coronary artery or coronary bypass graft suitable for percutaneous coronary intervention, in context of acute coronary syndrome or chronic coronary syndrome with evidence of ischemia by non-invasive study or pressure guidewire that can be treated by DES, and has at least 1 major or 2 minor Academic Research Consortium High Bleeding Risk criteria: Major criteria: 1. Anticipated use of long-term oral anticoagulation 2. Severe or end-stage Chronic Kidney Disease (CKD) (eGFR <30 mL/min) 3. Hemoglobin < 11 g/dL 4. Spontaneous bleeding requiring hospitalization or transfusion in the last 6 months, or any time, if recurrent. 5. Moderate or severe baseline thrombocytopenia (<100,000/uL) 6. Chronic bleeding diathesis 7. Liver cirrhosis with portal hypertension 8. Active malignancy (excluding nonmelanoma skin cancer) within the past 12 months 9. Previous spontaneous intracranial hemorrhage 10. Previous traumatic intracranial hemorrhage within the past 12 months 11. Presence of Brain Arteriovenous malformation (AVM) 12. Moderate or severe ischemic stroke (NIHSS score equal or more than 5) within the past 6 months 13. Non-deferrable major surgery on DAPT 14. Recent major surgery or major trauma within 30 days before PCI Minor Criteria: 1. Age 75 years old and older 2. Moderate CKD (eGFR 30-59 mL/min) 3. Hemoglobin 11 - 12.9 g/dL in men and 11 - 11.9 g/dL in women 4. Spontaneous bleeding requiring hospitalization or transfusion within the past 12 months, not meeting major criterion 5. Long term use of NSAIDs or steroids 6. Any ischemic stroke at any time not meeting major criterion Exclusion Criteria: STEMI undergoing primary PCI Cardiogenic shock or resuscitation with uncertain neurological status at arrival to PCI Unprotected left main lesion Reference diameter larger or shorter than available stents Life expectancy < 12 months In-stent restenosis o thrombosis of previous stent Inability to give written consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, non-inferiority clinical trial enrolling eligible subjects with high bleeding risk and coronary artery disease to be treated by percutaneous coronary intervention at the National Institute of Cardiology Ignacio Chávez in México. Included patients will have follow-up at the outpatient clinic through 1 year, until death or study exit, whichever comes first.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zotarolimus Eluting Stent<br>High Bleeding Risk patients to be treated with drug-eluting stents (DES). Includes both stable Coronary Artery Disease (CAD) and Acute Coronary Syndrome (ACS) patients undergoing elective PCI. | Device: Zotarolimus eluting stent<br>* Size (diameter and length) will be chosen at operator's discretion aided by simple angiography, QCA, or intravascular image; so that the lesion previously prepared and 2 mm at each end are covered by DES with an stent to artery ratio of 1.1. Post-dilatation will be performed when indicated. Device will be used by CE mark instructions. All patients will receive DAPT as follows: After a loading dose (if necessary) of aspirin and a P2Y12 inhibitor, aspirin 100 mg and a P2Y12 inhibitor daily will be indicated for 1 month in both ACS and Chronic Coronary Syndrome (CCS). Patients with high ischemic risk could be extended to 3 months. After DAPT, SAPT will be continued with the drug of choice, preferably P2Y12 inhibitor. Patients requiring chronic anticoagulation will receive triple therapy only during hospitalization. At release, an oral anticoagulant (NOAC preferred over VKA) will be indicated along with 6 months of SAPT with a P2Y12 inhibitor.<br>* Other names: Resolute Onyx, Zotarolimus eluting stent (Medtronic, Santa Rosa, CA, USA);|
| Experimental: Sirolimus Eluting Stent<br>High Bleeding Risk patients to be treated with drug-eluting stents (DES). Includes both stable CAD and ACS patients undergoing elective PCI. | Device: Sirolimus eluting stent<br>* Size (diameter and length) will be chosen at operator's discretion aided by simple angiography, QCA, or intravascular image; so that the lesion previously prepared and 2 mm at each end are covered by DES with an stent to artery ratio of 1.1. Post-dilatation will be performed when indicated. Device will be used in accordance with the CE mark instructions. All patients will receive DAPT as follows: After a loading dose (if necessary) of aspirin and a P2Y12 inhibitor, aspirin 100 mg and a P2Y12 inhibitor daily will be indicated for 1 month in both ACS and CCS. Patients with high ischemic risk could be extended to 3 months. After DAPT, SAPT will be continued with the drug of choice, preferably P2Y12 inhibitor. Patients requiring chronic anticoagulation will receive triple therapy only during hospitalization. At release, an oral anticoagulant (NOAC preferred over VKA) will be indicated along with 6 months of SAPT with a P2Y12 inhibitor.<br>* Other names: Ultimaster Tansei, Sirolimus eluting stent (Terumo; Tokyo, Japan);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Lesion Failure (TLF) | Rate of composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target lesion revascularization | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular death | Rate of death resulting from cardiovascular causes: Death caused by acute MI Death caused by sudden cardiac, including unwitnessed, death Death resulting from heart failure Death caused by stroke Death caused by cardiovascular procedures Death resulting from cardiovascular hemorrhage Death resulting from other cardiovascular cause Any MI not clearly attributable to a non- target vessel will be considered as target-vessel MI. Percutaneous coronary intervention (PCI) related MI is termed type 4a MI. | 12 months | 
| Myocardial Infarction related to the treated vessel | Rate of myocardial infarction related to the treated vessel (according to the 4th international definition of myocardial infarction): detection of an increase or decrease in cardiac troponin values with at least 1 of the values above the upper reference limit of the 99th percentile and at least 1 of the following conditions : Symptoms of acute myocardial ischemia. New ischemic changes in the electrocardiogram. Appearance of pathological Q waves. Imaging evidence of loss of viable myocardium or new regional abnormalities in myocardial wall mobility following a pattern compatible with ischemic etiology. Identification of a coronary thrombus by angiography with intracoronary imaging or by autopsy Any MI that cannot be clearly attributed to a vessel other than the revascularized one will be considered as MI related to the treated vessel. | 12 months | 
| Target Lesion Revascularization | Rate of repeated percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. | 12 months | 
| Target Vessel Failure (TVF) | Rate of TVF (composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target vessel revascularization) | 12 months | 
| Target Vessel Revascularization | Rate of repeat percutaneous intervention or surgical bypass of any segment of the target vessel | 12 months | 
| Non-cardiovascular death | Rate of any death that is not thought to be the result of a cardiovascular cause: Death resulting from malignancy Death resulting from pulmonary causes Death caused by infection (includes sepsis) Death resulting from gastrointestinal causes Death resulting from accident/trauma Death caused by other noncardiovascular organ failure 7. Death resulting from other noncardiovascular cause | 12 months | 
| Major Bleeding | Incidence of bleeding complications according to The Bleeding Academic Research Consortium 2 (BARC-2) scale: 3 or greater | 12 months | 
| Technical success | Rate of restoration of antegrade Thrombolysis In Myocardial Infarction (TIMI) flow 2 or 3 and a <30% residual stenosis. | Periprocedural | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short DAPT