Zotarolimus vs Sirolimus Eluting Stent in High Bleeding Risk

NCT05240781 | Unknown DMC

• 1 other identifier: 21-1277
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

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).

Conditions

High Bleeding Risk; Coronary Artery Disease; Percutaneous Coronary Intervention

Keywords

Short DAPT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Cardiovascular death

  12 months

• Myocardial Infarction related to the treated vessel

  12 months

• Target Lesion Revascularization

  12 months

• Target Vessel Failure (TVF)

  12 months

• Target Vessel Revascularization

  12 months

Study Arms (2)

Zotarolimus Eluting Stent

ACTIVE COMPARATOR

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

Sirolimus Eluting Stent

EXPERIMENTAL

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

Interventions

Zotarolimus eluting stent DEVICE

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.

Also known as: Resolute Onyx, Zotarolimus eluting stent (Medtronic, Santa Rosa, CA, USA)

Zotarolimus Eluting Stent

Sirolimus eluting stent DEVICE

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.

Also known as: Ultimaster, Sirolimus eluting stent (Terumo; Tokyo, Japan), Ultimaster Tansei, Sirolimus eluting stent (Terumo; Tokyo, Japan)

Sirolimus Eluting Stent

Eligibility Criteria

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

You may qualify if:

• 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:
• \. Anticipated use of long-term oral anticoagulation
• \. Severe or end-stage Chronic Kidney Disease (CKD) (eGFR \<30 mL/min)
• \. Hemoglobin \< 11 g/dL
• \. Spontaneous bleeding requiring hospitalization or transfusion in the last 6 months, or any time, if recurrent.
• \. Moderate or severe baseline thrombocytopenia (\<100,000/uL)
• \. Chronic bleeding diathesis
• \. Liver cirrhosis with portal hypertension
• \. Active malignancy (excluding nonmelanoma skin cancer) within the past 12 months
• \. Previous spontaneous intracranial hemorrhage
• \. Previous traumatic intracranial hemorrhage within the past 12 months
• \. Presence of Brain Arteriovenous malformation (AVM)
• \. Moderate or severe ischemic stroke (NIHSS score equal or more than 5) within the past 6 months
• \. Non-deferrable major surgery on DAPT

You may not qualify if:

• 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

Sponsors & Collaborators

• Instituto Nacional de Cardiologia Ignacio Chavez: lead

Study Sites (1)

Instituto Nacional de Cardiología "Ignacio Chávez"

Mexico City, 14080, Mexico

RECRUITING

Related Publications (11)

• Costa F, Van Klaveren D, Feres F, James S, Raber L, Pilgrim T, Hong MK, Kim HS, Colombo A, Steg PG, Bhatt DL, Stone GW, Windecker S, Steyerberg EW, Valgimigli M; PRECISE-DAPT Study Investigators. Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting. J Am Coll Cardiol. 2019 Feb 26;73(7):741-754. doi: 10.1016/j.jacc.2018.11.048.

  PMID: 30784667 BACKGROUND

• Costa F, Tijssen JG, Ariotti S, Giatti S, Moscarella E, Guastaroba P, De Palma R, Ando G, Oreto G, Zijlstra F, Valgimigli M. Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy. J Am Heart Assoc. 2015 Dec 7;4(12):e002524. doi: 10.1161/JAHA.115.002524.

  PMID: 26643501 BACKGROUND

• Urban P, Mehran R, Colleran R, Angiolillo DJ, Byrne RA, Capodanno D, Cuisset T, Cutlip D, Eerdmans P, Eikelboom J, Farb A, Gibson CM, Gregson J, Haude M, James SK, Kim HS, Kimura T, Konishi A, Laschinger J, Leon MB, Magee PFA, Mitsutake Y, Mylotte D, Pocock S, Price MJ, Rao SV, Spitzer E, Stockbridge N, Valgimigli M, Varenne O, Windhoevel U, Yeh RW, Krucoff MW, Morice MC. Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention. Circulation. 2019 Jul 16;140(3):240-261. doi: 10.1161/CIRCULATIONAHA.119.040167. Epub 2019 May 22.

  PMID: 31116032 BACKGROUND

• Varenne O, Cook S, Sideris G, Kedev S, Cuisset T, Carrie D, Hovasse T, Garot P, El Mahmoud R, Spaulding C, Helft G, Diaz Fernandez JF, Brugaletta S, Pinar-Bermudez E, Mauri Ferre J, Commeau P, Teiger E, Bogaerts K, Sabate M, Morice MC, Sinnaeve PR; SENIOR investigators. Drug-eluting stents in elderly patients with coronary artery disease (SENIOR): a randomised single-blind trial. Lancet. 2018 Jan 6;391(10115):41-50. doi: 10.1016/S0140-6736(17)32713-7. Epub 2017 Nov 1.

  PMID: 29102362 BACKGROUND

• Rissanen TT, Uskela S, Eranen J, Mantyla P, Olli A, Romppanen H, Siljander A, Pietila M, Minkkinen MJ, Tervo J, Karkkainen JM; DEBUT trial investigators. Drug-coated balloon for treatment of de-novo coronary artery lesions in patients with high bleeding risk (DEBUT): a single-blind, randomised, non-inferiority trial. Lancet. 2019 Jul 20;394(10194):230-239. doi: 10.1016/S0140-6736(19)31126-2. Epub 2019 Jun 13.

  PMID: 31204115 BACKGROUND

• Urban P, Meredith IT, Abizaid A, Pocock SJ, Carrie D, Naber C, Lipiecki J, Richardt G, Iniguez A, Brunel P, Valdes-Chavarri M, Garot P, Talwar S, Berland J, Abdellaoui M, Eberli F, Oldroyd K, Zambahari R, Gregson J, Greene S, Stoll HP, Morice MC; LEADERS FREE Investigators. Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk. N Engl J Med. 2015 Nov 19;373(21):2038-47. doi: 10.1056/NEJMoa1503943. Epub 2015 Oct 14.

  PMID: 26466021 BACKGROUND

• Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020 Mar 3;141(9):e139-e596. doi: 10.1161/CIR.0000000000000757. Epub 2020 Jan 29.

  PMID: 31992061 BACKGROUND

• Palmerini T, Bacchi Reggiani L, Della Riva D, Romanello M, Feres F, Abizaid A, Gilard M, Morice MC, Valgimigli M, Hong MK, Kim BK, Jang Y, Kim HS, Park KW, Colombo A, Chieffo A, Ahn JM, Park SJ, Schupke S, Kastrati A, Montalescot G, Steg PG, Diallo A, Vicaut E, Helft G, Biondi-Zoccai G, Xu B, Han Y, Genereux P, Bhatt DL, Stone GW. Bleeding-Related Deaths in Relation to the Duration of Dual-Antiplatelet Therapy After Coronary Stenting. J Am Coll Cardiol. 2017 Apr 25;69(16):2011-2022. doi: 10.1016/j.jacc.2017.02.029.

  PMID: 28427576 BACKGROUND

• Xu XM, Vestesson E, Paley L, Desikan A, Wonderling D, Hoffman A, Wolfe CD, Rudd AG, Bray BD. The economic burden of stroke care in England, Wales and Northern Ireland: Using a national stroke register to estimate and report patient-level health economic outcomes in stroke. Eur Stroke J. 2018 Mar;3(1):82-91. doi: 10.1177/2396987317746516. Epub 2017 Nov 30.

  PMID: 29900412 BACKGROUND

• Windecker S, Latib A, Kedhi E, Kirtane AJ, Kandzari DE, Mehran R, Price MJ, Abizaid A, Simon DI, Worthley SG, Zaman A, Hudec M, Poliacikova P, Abdul Ghapar AKB, Selvaraj K, Petrov I, Mylotte D, Pinar E, Moreno R, Fabbiocchi F, Pasupati S, Kim HS, Aminian A, Tie C, Wlodarczak A, Hur SH, Marx SO, Jankovic I, Brar S, Bousquette L, Liu M, Stone GW; ONYX ONE Investigators. Polymer-based or Polymer-free Stents in Patients at High Bleeding Risk. N Engl J Med. 2020 Mar 26;382(13):1208-1218. doi: 10.1056/NEJMoa1910021. Epub 2020 Feb 12.

  PMID: 32050061 RESULT

• Valgimigli M, Frigoli E, Heg D, Tijssen J, Juni P, Vranckx P, Ozaki Y, Morice MC, Chevalier B, Onuma Y, Windecker S, Tonino PAL, Roffi M, Lesiak M, Mahfoud F, Bartunek J, Hildick-Smith D, Colombo A, Stankovic G, Iniguez A, Schultz C, Kornowski R, Ong PJL, Alasnag M, Rodriguez AE, Moschovitis A, Laanmets P, Donahue M, Leonardi S, Smits PC; MASTER DAPT Investigators. Dual Antiplatelet Therapy after PCI in Patients at High Bleeding Risk. N Engl J Med. 2021 Oct 28;385(18):1643-1655. doi: 10.1056/NEJMoa2108749. Epub 2021 Aug 28.

  PMID: 34449185 RESULT

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Guering Eid-Lidt, MD

  Instituto Nacional de Cardiología "Ignacio Chávez"

  STUDY DIRECTOR

• Daniel F Zazueta, MD

  Instituto Nacional de Cardiología "Ignacio Chavez"

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel F Zazueta, MD

CONTACT

6666732911; drdanfeza@gmail.com

Guering Eid-Lidt, MD

CONTACT

5555732911; guering@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: February 15, 2022
• Study Start: September 29, 2021
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2025
• Last Updated: March 4, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)