Colchicine and Spironolactone in Patients With MI / SYNERGY Stent Registry

Phase 3

Completed

• Conditions: ST Elevation Myocardial Infarction; Non ST Elevation Myocardial Infarction
• Interventions: Drug: Colchicine; Drug: Spironolactone; Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent; Drug: Colchicine-Placebo; Drug: Spironolactone-Placebo

• Registration Number: NCT03048825
• Lead Sponsor: Population Health Research Institute

Brief Summary

The CLEAR SYNERGY trial will study the long term effects of treatments following PCI to treat myocardial infarction. These treatments address both the culprit artery (PCI with SYNERGY stent) as well as the non-culprit arteries (randomization to routine colchicine and spironolactone).

Detailed Description

This is a multicenter, international SYNERGY stent registry that is embedded within a randomized, blinded, double-dummy, 2x2 factorial design trial of colchicine versus placebo and spironolactone versus placebo in patients with myocardial infarction who have undergone primary percutaneous coronary intervention (PCI).

Study Timeline

• Study First Submitted: 2017-02-03
• Study First Submitted QC: 2017-02-07
• Study First Posted: 2017-02-09
• Study Start: 2018-02-01
• Primary Completion: 2024-08-09
• Study Completion: 2024-08-09
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7264

Inclusion Criteria

1. a) Patients with STEMI referred for PCI within 12 hours of symptom onset, have a culprit lesion amenable to stenting, and with planned SYNERGY stent implantation for SYNERGY registry

   OR

   b) Patients with STEMI referred for PCI within 48 hours of symptom onset, not prospectively enrolled in SYNERGY stent registry

   OR

   c) Patients with diagnosis of Non STEMI with ischemic symptoms and either Hs Troponin > or = 300x ULN or Troponin > or = 200x ULN who have undergone PCI with one of the following:

   i. LVEF< or =45% ii. Diabetes iii. Multivessel CAD defined as 50% stenosis in 2nd major epicardial vessel iv. Prior MI v. Age >60 years

2. Able to be enrolled/randomized within 72 hours of index PCI (however patients should be randomized as soon as possible after PCI)

3. Written informed consent

Exclusion Criteria

1. Age ≤18 years
2. Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception
3. Any medical, geographic, or social factor making study participation impractical or precluding required follow-up
4. Systolic blood pressure <90 mm Hg
5. Active diarrhea
6. Known allergy or contraindication to everolimus, the SYNERGY stent or any of its components
7. Unable to receive dual antiplatelet therapy
8. Any contraindication or known intolerance to colchicine or spironolactone
9. Requirement for colchicine or mineralocorticoid antagonist for another indication
10. History of cirrhosis or current severe hepatic disease
11. Current or planned use of any of: cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics
12. Creatinine clearance <30 mL/min/1.73 m2
13. Serum Potassium >5.0 meq/L

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Colchicine + Spironolactone +/- SYNERGY Stent	Spironolactone	Colchicine 0.5 mg tablet + Spironolactone 25 mg tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Colchicine + Spironolactone +/- SYNERGY Stent	SYNERGY Bioabsorbable Polymer Drug-Eluting Stent	Colchicine 0.5 mg tablet + Spironolactone 25 mg tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Spironolactone +/- SYNERGY Stent	SYNERGY Bioabsorbable Polymer Drug-Eluting Stent	Colchicine-placebo tablet + Spironolactone 25 mg tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Spironolactone +/- SYNERGY Stent	Colchicine-Placebo	Colchicine-placebo tablet + Spironolactone 25 mg tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Colchicine +/- SYNERGY Stent	Colchicine	Colchicine 0.5 mg tablet + Spironolactone-placebo tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Colchicine +/- SYNERGY Stent	SYNERGY Bioabsorbable Polymer Drug-Eluting Stent	Colchicine 0.5 mg tablet + Spironolactone-placebo tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Colchicine +/- SYNERGY Stent	Spironolactone-Placebo	Colchicine 0.5 mg tablet + Spironolactone-placebo tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Placebo +/- SYNERGY Stent	SYNERGY Bioabsorbable Polymer Drug-Eluting Stent	Colchicine-placebo tablet + Spironolactone-placebo tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Placebo +/- SYNERGY Stent	Colchicine-Placebo	Colchicine-placebo tablet + Spironolactone-placebo tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Placebo +/- SYNERGY Stent	Spironolactone-Placebo	Colchicine-placebo tablet + Spironolactone-placebo tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Colchicine + Spironolactone +/- SYNERGY Stent	Colchicine	Colchicine 0.5 mg tablet + Spironolactone 25 mg tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.
Spironolactone +/- SYNERGY Stent	Spironolactone	Colchicine-placebo tablet + Spironolactone 25 mg tablet. Trial participants who receive a SYNERGY Bioabsorbable Polymer Drug-Eluting Stent during their index PCI for STEMI will be included in the embedded SYNERGY Stent Registry.

Primary Outcome Measures

Name	Time	Method
Composite of cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia driven revascularization	through study completion, an estimated average of 3 years	The first occurrence of cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia driven revascularization in the colchicine comparison
Composite of cardiovascular death, new or worsening heart failure, recurrent myocardial infarction, or stroke (co-primary 2)	through study completion, an estimated average of 3 years	The first occurence of cardiovascular death, new or worsening heart failure, recurrent myocardial infarction, or stroke in the spironolactone comparison (co-primary 2)
Total composite events of cardiovascular death or new or worsening heart failure (co-primary 1)	through study completion, an estimated average of 3 years	Total composite of cardiovascular death or new or worsening heart failure in the spironolactone comparison (co-primary 1)
Major Adverse Cardiac Events (MACE)	up to 1 year	Major Adverse Cardiac Events (MACE) for SYNERGY Stent (defined as the composite of death, recurrent target vessel MI, stroke, or ischemia driven target vessel revascularization) compared to performance goal

Trial Locations

Locations (109)

Central Cardiology; 🇺🇸 Bakersfield, California, United States

Medstar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

University of Illinois; 🇺🇸 Chicago, Illinois, United States

Prairie Education & Research Cooperative; 🇺🇸 Springfield, Illinois, United States

Community Hospital; 🇺🇸 Munster, Indiana, United States

Lahey Hospital and Medical Center; 🇺🇸 Burlington, Massachusetts, United States

New Mexico Heart Institute; 🇺🇸 Albuquerque, New Mexico, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

The Christ Hospital Lindner Research Center; 🇺🇸 Cincinnati, Ohio, United States

Penn State Health Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

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