SYNergy Stent® System Implantation With Mandatory Intra-VascularUltra-Sound Guidance and Dual Anti-Platelet Therapy (SYNIVUS-DAPT)

SYNergy Stent® System Implantation With Mandatory Intra-VascularUltra-Sound Guidance to Examine the Safety of Cessation of Dual Anti-Platelet Therapy in High Bleeding Risk Patients at One Month

The purpose of this study is to see if one month of dual antiplatelet therapy (DAPT) combined with the placement of the Synergy® Stent with IVUS (intravascular ultrasound) is safe for patients who are at high risk of bleeding (HBR).

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; Atherosclerosis; Stent Placement
• Intervention / Treatment: Drug: Dual Antiplatelet (DAPT) Therapy; Device: The Synergy® stent

Detailed Description

DAPT or Dual Antiplatelet Therapy is a combination of two medications given after a percutaneous coronary intervention (PCI) with a drug eluting stent. DAPT is used to help make the platelets in your blood slick so they don't clump or stick together. If the platelets stick together and form a blood clot in the stent it is called a stent thrombosis and will cause an immediate heart attack or MI.

The medications used for DAPT are low dose Aspirin (81mg) and one of three (3) antiplatelet medications: ticagrelor (Brilinta), clopidogrel (Plavix) or prasugrel (Effient) . The standard length of time to take DAPT after a stent placement is 6 months to 1 year. Dapt is associated with an increased risk of bleeding. Because you are considered to be at a high risk for bleeding due to one or a combination of reasons this study is trying to determine if a shorter use of DAPT in combination with the Synergy® stent and an imaging tool called IVUS used during your PCI procedure is safe and effective to reduce the potential for serious bleeding events and early stent thrombosis.

The Synergy® stent was chosen because of its enhanced method of healing and reduced inflammation of the artery after placement. Because of this the Synergy stent may be a better choice for patients who are at high risk for bleeding and could benefit from a shortened period of DAPT.

Intravascular ultrasound or IVUS provides a visual image of the inside of the coronary artery. It is used in patients undergoing PCI or stent placement for a few reasons; prior to placing the stent it is used to measure the artery's width to select the proper size diameter of a stent, also the length of the blockage to select the appropriate length of the stent and to visualize the amount of narrowing or blockage. After the stent is placed IVUS is used to make sure the stent itself is fully expanded and sits up against the wall of the artery. This is called apposition. If stents are not fully expanded and sit up against the wall of the artery early reblockage may occur. In short the IVUS aids in the ideal placement of the stent.

By using the combination of the Synergy® Stent with the IVUS the expectation is to safely decrease the length of time you take DAPT from 6-12 months to 1 month. With the benefit of decreasing the risk of bleeding events.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital, Corrigan Minehan Heart Center
  • New York
    • New York, New York, United States, 10075
      • Northwell Hospital Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 bleeding associated with >1 months of DAPT outweighs the benefit,
• need for chronic or lifelong anticoagulation therapy
• 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 ≥20,000/μLto ≤100,000/μL
• In the opinion of investigator, patient is at significant risk of falling
• Patient abuses drugs or alcohol
• Hemoglobin ≤11.0 u/dl 2. Subject must be 18 years of age 3. Subject must be able to take study required dual antiplatelet therapy (1 month of P2Y12 inhibitor and aspirin, 13 months of antiplatelet monotherapy) 4. Subject is willing to comply with all protocol requirements, including agreement to stop taking P2Y12 inhibitor at the 1-month milestone if eligible per protocol 5. Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific procedures are performed

Angiographic Inclusion Criteria:

1. Subject must have had implantation of at least one Synergy Stent and the use of Boston Scientific IVUS for guided stent implantation

2. All implanted stents must be post dilated and must meet the following IVUS success criteria:

   • treated lesions in which the stent cross sectional area exceeds the distal reference cross sectional area
   • if the stent cross sectional area is less than the distal reference cross sectional area additional post-dilatation must be performed, followed by IVUS
   • above IVUS criteria must be met after the 2nd post dilatation NOTE: if the IVUS criteria is not met after the 2 post dilatation the patient is excluded
3. Stent procedure performed by an approved investigator
4. Vessel diameter ≥ 2.25 mm and ≤4.0 mm and lesion length ≤34mm
5. Pre-dilatation is up to the discretion of the investigator

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 Stent during the index procedure
4. Subject with a planned staged procedure >7 days following the index procedure. (Note: Planned staged procedures are allowed if performed within 7 days of the index procedure and only when SYNERGY stents are used for both the index and staged procedure). Discontinuation of DAPT should occur 1 month after the last PCI procedure is completed.
5. A staged procedure cannot in a 3rd epicardial vessel if 2 epicardial vessels were treated during the index procedure
6. 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)
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 12 months following the index procedure (Note: registry, observational, data collection studies are not exclusionary)

11. Subject is judged inappropriate for discontinuation from P2Y12 inhibitor use at 1 month, due to another condition requiring chronic P2Y12 inhibitor use

    • if at the 30 day visit, the patient has had a peri-procedural NSTEMI with an enzyme elevation >5% of the upper 99th percentile of either CK-MB or Troponin, the patient should not be taken off DAPT
12. Subject with planned surgery or procedure necessitating discontinuation of P2Y12 inhibitor within 1 month 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 12 months
15. Subject with implantation of a drug-eluting stent other than SYNERGY Stent within 11 months prior to index procedure
16. Have been previously consented for this trial and screen failed
17. Any other clinically significant comorbidities, which in the judgement of the investigator, could compromise compliance with the protocol, interfere with interpretation of the study results, or predispose the patient to safety risks.

Angiographic Exclusion Criteria:

1. Target lesion(s) is located within a saphenous vein graft or an arterial graft
2. TIMI flow 0 (total occlusion)
3. Target lesion(s) is located in the left main
4. Potential Target lesion(s) that involve a complex bifurcation (i.e. bifurcation lesion requiring treatment with more than one stent)
5. Thrombus, or possible thrombus, present in the target vessel (by visual estimate)
6. Patients requiring a treatment of more than two native epicardial vessels
7. More than three lesions in two epicardial vessels unless they can be covered in one stent
8. In-stent restenosis of target lesion
9. Treatment of non-target lesions or lesions not treated with a Synergy stent
10. Subject who did not receive Boston Scientific IVUS guided stent implantation and assessment
11. Any target lesion that has not been post dilated and has not had post dilatation IVUS

12. Patients who do not meet the following IVUS success criteria:

    • target lesion(s) in which the stent cross sectional area is less than the distal reference cross sectional area and additional post-dilatation should be performed, followed by repeat IVUS.

NOTE: if the IVUS criteria is not met after the 2nd post dilatation, the patient is excluded

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: PCI with 30 day DAPT Therapy; Single group of patients undergoing IVUS stent placement for PCI with 30 day DAPT therapy regimen. DAPT therapy consists of Aspirin (325 mg loading dose [if applicable] and 81 mg for maintenance dose) and P2Y12 Inhibitor (INFO ABOUT THE DRUGS)

Drug: Dual Antiplatelet (DAPT) Therapy; DAPT - one of three (3) antiplatelet medications: ticagrelor (Brilinta), clopidogrel (Plavix) or prasugrel (Effient) with Aspirin. Aspirin loading dose (LD) = 325 mg. Aspirin maintenance dose (MD) = 81 mg. P2Y12 Inhibitor Loading Dose (investigator preference): Clopidogrel 600 mg PO x 1 or 75 mg PO daily x 4; Prasugrel 60 mg PO x 1; Ticagrelor 180 mg PO x 1. P2Y12 Inhibitor Maintenance Dose (investigator preference): Clopidogrel 75 mg PO daily; Prasugrel 10 mg PO daily; Ticagrelor 90 mg PO BID.; Other Names: Clopidogrel (Plavix); Ticagrelor (Brilinta); Prasugrel (Effient) with Aspirin; Device: The Synergy® stent; IVUS guided stent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of cardiac death	Rate of cardiac death from 1 to 13 months post-index procedure in the "as treated" (eligible for 30 day DAPT cessation) population.	1 to 13 months
Rate of myocardial infarction	Rate of myocardial infarction (SCAI definition) from 1 to 13 months post-index procedure in the overall enrolled "intent-to-treat" patient population	1 to 13 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Academic Research Consortium (ARC) definite/probable stent thrombosis (ST)	Rate of Academic Research Consortium (ARC) definite/probable stent thrombosis (ST) involving SYNERGY Stent® from 1 to 13 months post-index procedure	1 to 13 months
Rate of major bleeding	Rate of major bleeding (GUSTO severe/life threatening + moderate)	1 to 13 months
Ischemia-Driven (ID) Target Lesion Revascularization	Angina Assessment	1 to 13 months
ID Target Vessel Revascularization,	Angina Assessment	1 to 13 months
Target Lesion Failure	Angina Assessment	1 to 13 months
Target Vessel Failure	Angina Assessment	1 to 13 months
All-Cause Death	Angina Assessment	1 to 13 months
All-Cause MI	Angina Assessment	1 to 13 months

Collaborators and Investigators

• Sponsor: HonorHealth Research Institute
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: David Rizik, MD, HonorHealth Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2018
• Primary Completion (Actual): December 31, 2021
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 23, 2018
• First Submitted That Met QC Criteria: July 23, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Ischemia; peripheral vascular disease (PVD)
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Atherosclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: SYNIVUS-DAPT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes