Colchicine and Spironolactone in Patients With MI / SYNERGY Stent Registry

Study Overview
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Brief Summary
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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
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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).

Official Title
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A 2x2 Factorial Randomized Controlled Trial of Colchicine and Spironolactone in Patients With Myocardial Infarction / SYNERGY Stent Registry - Organization to Assess Strategies for Ischemic Syndromes 9

Conditions
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ST Elevation Myocardial Infarction, Non ST Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: Colchicine
* Drug: Spironolactone
* Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent
* Drug: Colchicine-Placebo
* Drug: Spironolactone-Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Able to be enrolled/randomized within 72 hours of index PCI (however patients should be randomized as soon as possible after PCI) Written informed consent Exclusion Criteria: Age ≤18 years Pregnancy, breastfeeding, or women of childbearing potential who are not using an effective method of contraception Any medical, geographic, or social factor making study participation impractical or precluding required follow-up Systolic blood pressure <90 mm Hg Active diarrhea Known allergy or contraindication to everolimus, the SYNERGY stent or any of its components Unable to receive dual antiplatelet therapy Any contraindication or known intolerance to colchicine or spironolactone Requirement for colchicine or mineralocorticoid antagonist for another indication History of cirrhosis or current severe hepatic disease Current or planned use of any of: cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics Creatinine clearance <30 mL/min/1.73 m2 Serum Potassium >5.0 meq/L

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine + Spironolactone +/- SYNERGY Stent<br>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. | Drug: Colchicine<br>* Colchicine 0.5 mg once daily<br>Drug: Spironolactone<br>* Spironolactone 25 mg once daily<br>Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent<br>* Trial participants who receive a SYNERGY™ Bioabsorbable Polymer Drug-Eluting (everolimus) Stent during their index PCI for STEMI will be included in the SYNERGY Stent Registry.<br>|
| Experimental: Spironolactone +/- SYNERGY Stent<br>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. | Drug: Spironolactone<br>* Spironolactone 25 mg once daily<br>Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent<br>* Trial participants who receive a SYNERGY™ Bioabsorbable Polymer Drug-Eluting (everolimus) Stent during their index PCI for STEMI will be included in the SYNERGY Stent Registry.<br>Drug: Colchicine-Placebo<br>* Matching Colchicine-placebo once daily<br>|
| Experimental: Colchicine +/- SYNERGY Stent<br>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. | Drug: Colchicine<br>* Colchicine 0.5 mg once daily<br>Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent<br>* Trial participants who receive a SYNERGY™ Bioabsorbable Polymer Drug-Eluting (everolimus) Stent during their index PCI for STEMI will be included in the SYNERGY Stent Registry.<br>Drug: Spironolactone-Placebo<br>* Matching Spironolactone-Placebo once daily<br>|
| Placebo Comparator: Placebo +/- SYNERGY Stent<br>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. | Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent<br>* Trial participants who receive a SYNERGY™ Bioabsorbable Polymer Drug-Eluting (everolimus) Stent during their index PCI for STEMI will be included in the SYNERGY Stent Registry.<br>Drug: Colchicine-Placebo<br>* Matching Colchicine-placebo once daily<br>Drug: Spironolactone-Placebo<br>* Matching Spironolactone-Placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Cardiac Events (MACE) | 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 | up to 1 year | 
| Composite of cardiovascular death, recurrent myocardial infarction, or stroke | The first occurrence of cardiovascular death, recurrent myocardial infarction, or stroke in the colchicine comparison | through study completion, an estimated average of 2 years | 
| Composite of cardiovascular death or new or worsening heart failure | The first occurrence of cardiovascular death or new or worsening heart failure in the spironolactone comparison | through study completion, an estimated average of 2 years |