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Zotarolimus vs Sirolimus Eluting Stent in High Bleeding Risk (ZEVS-HBR)

Primary Purpose

High Bleeding Risk, Coronary Artery Disease, Percutaneous Coronary Intervention

Status

Recruiting

Phase

Not Applicable

Locations

Mexico

Study Type

Interventional

Intervention

Zotarolimus eluting stent

Sirolimus eluting stent

About this trial

This is an interventional treatment trial for High Bleeding Risk focused on measuring Short DAPT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Instituto Nacional de Cardiología "Ignacio Chávez"Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Zotarolimus Eluting Stent

Sirolimus Eluting Stent

Arm Description

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.

High Bleeding Risk patients to be treated with drug-eluting stents (DES). Includes both stable CAD and ACS patients undergoing elective PCI.

Outcomes

Primary Outcome Measures

Target Lesion Failure (TLF)

Rate of composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target lesion revascularization

Secondary Outcome Measures

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.

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.

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.

Target Vessel Failure (TVF)

Rate of TVF (composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target vessel revascularization)

Target Vessel Revascularization

Rate of repeat percutaneous intervention or surgical bypass of any segment of the target vessel

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

Major Bleeding

Incidence of bleeding complications according to The Bleeding Academic Research Consortium 2 (BARC-2) scale: 3 or greater

Technical success

Rate of restoration of antegrade Thrombolysis In Myocardial Infarction (TIMI) flow 2 or 3 and a <30% residual stenosis.

Full Information

NCT ID

NCT05240781

First Posted

February 4, 2022

Last Updated

February 17, 2022

Sponsor

Instituto Nacional de Cardiologia Ignacio Chavez

1. Study Identification

Unique Protocol Identification Number

NCT05240781

Brief Title

Zotarolimus vs Sirolimus Eluting Stent in High Bleeding Risk

Acronym

ZEVS-HBR

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 29, 2021 (Actual)

Primary Completion Date

February 28, 2024 (Anticipated)

Study Completion Date

February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Instituto Nacional de Cardiologia Ignacio Chavez

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

High Bleeding Risk, Coronary Artery Disease, Percutaneous Coronary Intervention

Keywords

Short DAPT

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

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

ParticipantOutcomes Assessor

Masking Description

Randomized treatment will not be revealed to patient or data analyst at any time during procedure or afterwards until follow-up and analysis has been done.

Allocation

Randomized

Enrollment

280 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Zotarolimus Eluting Stent

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Sirolimus Eluting Stent

Arm Type

Experimental

Arm Description

High Bleeding Risk patients to be treated with drug-eluting stents (DES). Includes both stable CAD and ACS patients undergoing elective PCI.

Intervention Type

Device

Intervention Name(s)

Zotarolimus eluting stent

Other Intervention Name(s)

Resolute Onyx, Zotarolimus eluting stent (Medtronic, Santa Rosa, CA, USA)

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Sirolimus eluting stent

Other Intervention Name(s)

Ultimaster, Sirolimus eluting stent (Terumo; Tokyo, Japan), Ultimaster Tansei, Sirolimus eluting stent (Terumo; Tokyo, Japan)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Target Lesion Failure (TLF)

Description

Rate of composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target lesion revascularization

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Cardiovascular death

Description

Time Frame

12 months

Title

Myocardial Infarction related to the treated vessel

Description

Time Frame

12 months

Title

Target Lesion Revascularization

Description

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.

Time Frame

12 months

Title

Target Vessel Failure (TVF)

Description

Rate of TVF (composed of cardiovascular death, myocardial infarction related to the treated vessel or ischemia driven target vessel revascularization)

Time Frame

12 months

Title

Target Vessel Revascularization

Description

Rate of repeat percutaneous intervention or surgical bypass of any segment of the target vessel

Time Frame

12 months

Title

Non-cardiovascular death

Description

Time Frame

12 months

Title

Major Bleeding

Description

Incidence of bleeding complications according to The Bleeding Academic Research Consortium 2 (BARC-2) scale: 3 or greater

Time Frame

12 months

Title

Technical success

Description

Rate of restoration of antegrade Thrombolysis In Myocardial Infarction (TIMI) flow 2 or 3 and a <30% residual stenosis.

Time Frame

Periprocedural

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Daniel F Zazueta, MD

Phone

6666732911

Ext

1235

drdanfeza@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Guering Eid-Lidt, MD

Phone

5555732911

Ext

1235

guering@yahoo.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Guering Eid-Lidt, MD

Organizational Affiliation

Instituto Nacional de Cardiología "Ignacio Chávez"

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Daniel F Zazueta, MD

Organizational Affiliation

Instituto Nacional de Cardiología "Ignacio Chavez"

Official's Role

Principal Investigator

Facility Information:

Facility Name

Instituto Nacional de Cardiología "Ignacio Chávez"

City

Ciudad de México

ZIP/Postal Code

14080

Country

Mexico

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel F Zazueta, MD

Phone

5555732911

Ext

1235

drdanfeza@gmail.com

First Name & Middle Initial & Last Name & Degree

Guering Eid-Lidt, MD

Phone

5555732911

Ext

1235

guering@yahoo.com

12. IPD Sharing Statement

Plan to Share IPD

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Zotarolimus vs Sirolimus Eluting Stent in High Bleeding Risk

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