EVOLVE Short DAPT Study

A Prospective, Multicenter, Single-arm Study Designed to Assess the Safety of 3-month Dual Antiplatelet Therapy (DAPT) in Subjects at High Risk for Bleeding Undergoing Percutaneous Coronary Intervention (PCI) With the SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System

The EVOLVE Short DAPT Study is a prospective, multicenter, single-arm study designed to assess the safety of 3-month DAPT in subjects at high risk for bleeding undergoing PCI with a SYNERGY Stent System.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: 3 months of dual antiplatelet therapy (DAPT); Device: SYNERGY Stent System

Detailed Description

The primary objective of the EVOLVE Short DAPT Study is to assess the safety of 3-month dual antiplatelet therapy (DAPT) in subjects at high risk for bleeding undergoing percutaneous coronary intervention (PCI) with the SYNERGY Stent System.

The study will be conducted up to 120 sites worldwide in the United States, Europe, Japan, and Brazil with planned enrollment of up to 2,250 subjects. Clinical follow-up will be required at the following time points: 3 months, 6 months, 12 months and 15 months post index procedure.

Subjects must be treated with one of the following P2Y12 inhibitors (clopidogrel, prasugrel, or ticagrelor) for 3 months following the index procedure. Subjects must be treated with aspirin for the duration of the trial. The minimum daily maintenance dose of aspirin should be 75-100 mg.

Subjects are eligible for discontinuation of P2Y12 inhibitor at 3 months if they meet both of the following criteria: subject was treated with 3 months of study required antiplatelet therapy post index procedure; and subject was free from events (stroke, MI, PCI, coronary artery bypass graft [CABG], and stent thrombosis) between the index procedure and the 3 month visit.

Subjects are not eligible for discontinuation of P2Y12 inhibitor at 3 months if any of the following criteria are met: subject who experiences a stroke, MI, PCI, CABG and/or stent thrombosis, during the 0-3 month period (between the date of the index procedure and the date of the 3-month follow-up visit); or subject who is non-compliant with study required antiplatelet therapy during the 0-3 month period (between the date of the index procedure and the date of the 3-month follow-up visit); or subject judged inappropriate for discontinuation from P2Y12 inhibitor use at 3 months due to another condition requiring chronic P2Y12 inhibitor use.

All enrolled subjects who receive a SYNERGY stent must be followed at all milestones through 15-months, regardless of eligibility to discontinue P2Y12 inhibitor. Following the 3-month milestone, subjects who experience MI or stent thrombosis events should be treated per the investigator's discretion and should be followed through the 15-month visit.

• Study Type: Interventional
• Enrollment (Actual): 2009
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05403-000
    • Instituto do Coracao (InCor)
  • São Paulo, Brazil, 04012-909
    • Instituto de Cardiologia Dante Pazzanese
• Germany
  • Bad Krozingen, Germany, 79189
    • Herzzentrum Bad Krozingen
  • Bad Segeberg, Germany, 23795
    • Herz-Kreislauf-Zentrum Segeberger Kliniken GmbH
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Jena, Germany, 07740
    • Uni Jena
• Japan
  • Kurume-shi, Japan, 830-0011
    • Kurume University Hospital
  • Osaka, Japan
    • Osaka Saiseikai Nakatsu Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 814-0001
      • Fukuoka Sanno Hospital
  • Iwate-ken
    • Morioka-shi, Iwate-ken, Japan, 020-8505
      • Iwate Medical University Hospital
  • Kanagawa
    • Isehara-shi, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
    • Kamakura-shi, Kanagawa, Japan, 247-0072
      • Shonan Kamakura General Hospital
    • Yokohama-shi, Kanagawa, Japan, 230-8765
      • Saiseikai Yokohama-City Eastern Hospital
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-8643
      • Mitsui Memorial Hospital
    • Itabashi-ku, Tokyo, Japan, 173-8606
      • Teikyo University Hospital
    • Meguro-ku, Tokyo, Japan, 153-8515
      • Toho University Ohashi Medical Center
• Latvia
  • Riga, Latvia, LV-1002
    • P. Stradins University Hospital
• Sweden
  • Falun, Sweden, 79182
    • Falu Lasarett
  • Karlstad, Sweden, 65185
    • Karlstadt Central Hospital
  • Malmo, Sweden, SE-214 28
    • Skåne University Hospital
• Switzerland
  • Fribourg, Switzerland, 1708
    • Hospital Cantonal Fribourg
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital & Medical Center
    • Phoenix, Arizona, United States, 85006
      • Banner Good Samaritan Regional Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Heart Hospital
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Medical Center (Little Rock)
  • California
    • Bakersfield, California, United States, 93301
      • Bakersfield Memorial Hospital
    • Los Angeles, California, United States, 90048
      • Cedars - Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • USC Medical Center
    • Mountain View, California, United States, 94040
      • El Camino Hospital
    • Riverside, California, United States, 92506
      • HCA Riverside Community Hospital
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center, Sacramento
    • San Francisco, California, United States, 94115
      • Kaiser Foundation Hospital - San Francisco
    • Walnut Creek, California, United States, 94598
      • John Muir Medical Center
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates, PC
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Atlantis, Florida, United States, 33462
      • JFK Medical Center
    • Clearwater, Florida, United States, 33756
      • Morton Plant Mease Healthcare System
    • Gainesville, Florida, United States, 32605
      • North Florida Regional Medical Center
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
    • Ocala, Florida, United States, 34471
      • MediQuest Research at Munroe Regional Medical Center
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Sebring, Florida, United States, 33870
      • Florida Hospital Heartland Medical Center
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
  • Georgia
    • Augusta, Georgia, United States, 30901
      • University Hospital
    • Macon, Georgia, United States, 31201
      • Medical Center of Central Georgia
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Naperville, Illinois, United States, 60566
      • Edward Hospital
    • Springfield, Illinois, United States, 62701
      • St. John's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Foundation Hospital
  • Indiana
    • Beech Grove, Indiana, United States, 46237
      • Franciscan St. Francis Hospital
    • Fort Wayne, Indiana, United States, 46804
      • Northern Indiana Research Alliance - Lutheran Hospital
    • Indianapolis, Indiana, United States, 46250
      • Community Heart and Vascular Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Mercy Hospital Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital and St. Mary's Healthcare
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Cardiovascular Research, LLC
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Union Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • St. Mary's Duluth Clinic Regional Heart Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
    • Saint Paul, Minnesota, United States, 55102
      • HealthEast St. Joseph's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65802
      • Cox Medical Centers
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-1000
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart and Lung Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Memorial Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Presbyterian Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center/ NewYork Presbyterian Hospital
    • Syracuse, New York, United States, 13202
      • St. Joseph's Hospital Health Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Raleigh, North Carolina, United States, 27610
      • Wake Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital
    • Cincinnati, Ohio, United States, 45219
      • Lindner Center for Research and Education at Christ Hospital
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research and Innovation Institute - Riverside Methodist Hospital
    • Columbus, Ohio, United States, 03210
      • Ohio State University Medical Center
    • Toledo, Ohio, United States, 43608
      • Mercy St. Vincent Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart Hospital
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Hospital
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Sisters of Charity Providence Hospital
    • Greenville, South Carolina, United States, 29605
      • University Medical Center-Greenville Memorial Hospital
    • Myrtle Beach, South Carolina, United States, 29572
      • Grand Strand Regional Medical Center
  • Tennessee
    • Jackson, Tennessee, United States, 38301
      • Jackson-Madison County General Hospital
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital
    • Nashville, Tennessee, United States, 37203
      • Centennial Medical Center
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor Heart & Vascular Hospital
    • Houston, Texas, United States, 77030
      • St. Luke's Episcopal Hospital
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
    • Round Rock, Texas, United States, 78681
      • St. David's Round Rock Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Winchester, Virginia, United States, 26015
      • Winchester Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Charleston Area Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center
    • Wausau, Wisconsin, United States, 54401
      • Aspirus Heart and Vascular Institute - Research and Education

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is considered at high risk for bleeding, defined as meeting one or more of the following criteria at the time of enrollment:

   • ≥ 75 years of age and, in the opinion of the investigator, the risk of major bleeding associated with >3 months of DAPT outweighs the benefit,
   • need for chronic or lifelong anticoagulation,
   • history of major bleeding (severe/life threatening or moderate bleeding based on the GUSTO classification) within 12 months of the index procedure,
   • history of stroke (ischemic or hemorrhagic),
   • renal insufficiency (creatinine ≥2.0 mg/dl) or failure (dialysis dependent),
   • platelet count ≤100,000/μL
2. Subject must be at least 18 years of age
3. Subject must have had implantation of at least one SYNERGY stent within the preceding 3 calendar days
4. Subject must be able to take study required antiplatelet therapy (as required per protocol)
5. Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at the 3-month milestone, if eligible per protocol
6. Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any study-specific procedures are performed
7. For subjects less than 20 years of age enrolled at a Japanese site, the subject/ the subject's legal representative must provide written informed consent before any study-specific tests or procedures are performed

Exclusion Criteria:

1. Subject with an indication for the index procedure of acute ST elevation MI (STEMI)
2. Subject with an indication for the index procedure of Non ST elevation MI (NSTEMI), based on the 3rd Universal MI definition
3. Subject with treatment with another coronary stent, other than SYNERGY, during the index procedure
4. Subject with planned staged procedures. (Note: Planned staged procedures are allowed if performed within 7 days and with only SYNERGY stents).
5. Subject has a known allergy to contrast (that cannot be adequately pre-medicated), the SYNERGY stent system or protocol-required concomitant medications (e.g., everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors and aspirin)
6. Subject with implantation of a drug-eluting stent within 9 months prior to index procedure
7. Subject previously treated at any time with intravascular brachytherapy
8. Subject has an active peptic ulcer or active gastrointestinal (GI) bleeding
9. Subject is participating in an investigational drug or device clinical trial that has not reached its primary endpoint (Note: registry, observational, data collection studies are not exclusionary)
10. Subject intends to participate in an investigational drug or device clinical trial within 15 months following the index procedure (Note: registry, observational, data collection studies are not exclusionary)
11. Subject judged inappropriate for discontinuation from P2Y12 inhibitor use at 3 months, due to another condition requiring chronic P2Y12 inhibitor use
12. Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 3 months following index procedure
13. Subject is a woman who is pregnant or nursing
14. Subject with a current medical condition with a life expectancy of less than 15 months
15. Target lesion(s) is located in the left main
16. Target lesion(s) is located within 3 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCx) coronary artery by visual estimate
17. Subject has unprotected left main coronary artery disease ( > 50% diameter stenosis)
18. Planned treatment of more than 3 lesion
19. Planned treatment of lesions in more than 2 major epicardial vessels
20. Target lesion(s) treated that involve complex bifurcation (i.e. bifurcation lesion requiring treatment with more than one stent)
21. Target lesion(s) is restenotic from a previous stent implantation
22. Target lesion(s) is located within a saphenous vein graft or an arterial graft
23. Target lesion(s) with a TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing
24. Thrombus, or possible thrombus, present in the target vessel (by visual estimate)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SYNERGY stent + 3 month DAPT; Subject with implantation of at least one SYNERGY stent within the preceding 3 calendar days that takes the required dual antiplatelet therapy (3 months of P2Y12 inhibitor, 15 months of aspirin)	Drug: 3 months of dual antiplatelet therapy (DAPT); 3 months of P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) plus 15-months of aspirin; Device: SYNERGY Stent System; SYNERGY Everolimus-Eluting Platinum Chromium Coronary Stent System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Death or Myocardial Infarction (MI)	Rate of death or myocardial infarction	3 to 15 months
Number of Participants Who Experienced Stent Thrombosis (ST)	Rate of stent thrombosis: definite + probable, using the Academic Research Consortium (ARC) definition Confirmed/Definite (is considered either angiographic confirmed or pathologic confirmed) Probable Clinical definition of probable stent thrombosis is considered to have occurred in the following cases: Any unexplained death within the first 30 days; Irrespective of the time after the index procedure and MI in the absence of any obvious cause which is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis Possible Clinical definition of possible stent thrombosis is considered to have occurred with any unexplained death beyond 30 days.	3 to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced Major Bleeding	Rate of Bleeding, per Bleeding Academic Consortium definition (BARC2, 3a, 3b, 3c, 4, 5a and 5b); Type 0: No Bleeding; Type 1: Bleeding that is not actionable and does not cause the patient to seek treatment; Type 2: Any clinically overt sign of hemorrhage that "is actionable" and requires diagnostic studies, hospitalization, or treatment by a health care professional; Type 3a: Overt bleeding plus hemoglobin drop of 3 to < 5 g/dL (provided hemoglobin drop is related to bleed); transfusion with overt bleeding; Type 3b: Overt bleeding plus hemoglobin drop ≥5 g/dL (provided hemoglobin drop is related to bleed); cardiac tamponade; bleeding requiring surgical intervention for control; bleeding requiring IV vasoactive agents; Type 3c: Intracranial hemorrhage confirmed by autopsy, imaging, or lumbar puncture; intraocular bleed compromising vision; Type 4: CABG-related bleeding within 48 hours; Type 5a: Probable fatal bleeding; Type 5b: Definite fatal bleeding	3 to 15 months

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Ajay Kirtane, MD, Columbia University Medical Center/ NewYork Presbyterian Hospital; Principal Investigator: Stephan Windecker, Prof, MD, Inselspital - Universitätsspital Bern

Publications and helpful links

General Publications

• Kirtane AJ, Stoler R, Feldman R, Neumann FJ, Boutis L, Tahirkheli N, Toelg R, Othman I, Stein B, Choi JW, Windecker S, Yeh RW, Dauerman HL, Price MJ, Underwood P, Allocco D, Meredith I, Kereiakes DJ. Primary Results of the EVOLVE Short DAPT Study: Evaluation of 3-Month Dual Antiplatelet Therapy in High Bleeding Risk Patients Treated With a Bioabsorbable Polymer-Coated Everolimus-Eluting Stent. Circ Cardiovasc Interv. 2021 Mar;14(3):e010144. doi: 10.1161/CIRCINTERVENTIONS.120.010144. Epub 2021 Mar 1.
• Balanescu DV, Aziz MK, Donisan T, Palaskas N, Lopez-Mattei J, Hassan S, Kim P, Song J, Ntim W, Cilingiroglu M, Marmagkiolis K, Iliescu C. Cancer treatment resumption in patients with new-generation drug-eluting stents. Coron Artery Dis. 2021 Jun 1;32(4):295-301. doi: 10.1097/MCA.0000000000000986.
• Mauri L, Kirtane AJ, Windecker S, Yeh RW, Dauerman HL, Price MJ, Christen T, Allocco DJ, Meredith IT, Kereiakes DJ. Rationale and design of the EVOLVE Short DAPT Study to assess 3-month dual antiplatelet therapy in subjects at high risk for bleeding undergoing percutaneous coronary intervention. Am Heart J. 2018 Nov;205:110-117. doi: 10.1016/j.ahj.2018.08.004. Epub 2018 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2016
• Primary Completion (Actual): July 17, 2019
• Study Completion (Actual): July 17, 2019

Study Registration Dates

• First Submitted: November 12, 2015
• First Submitted That Met QC Criteria: November 12, 2015
• First Posted (Estimate): November 16, 2015

Study Record Updates

• Last Update Posted (Actual): September 25, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: S2073