Colchicine and Spironolactone in Patients with MI / SYNERGY Stent Registry (CLEAR SYNERGY)

Population Health Research Institute (PHRI)

Status and phase: Completed; Phase 3

Conditions: ST Elevation Myocardial Infarction; Non ST Elevation Myocardial Infarction

Treatments: Drug: Spironolactone; Drug: Colchicine; Drug: Spironolactone-Placebo; Drug: Colchicine-Placebo; Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03048825

OASIS-9 (Other Identifier)

CLSYN.1702

Details and patient eligibility

About

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).

Full 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).

Enrollment: 7,264 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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7,264 participants in 4 patient groups, including a placebo group

Colchicine + Spironolactone +/- SYNERGY Stent

Active Comparator group

Description:

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.

Treatment:

Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Drug: Colchicine

Drug: Spironolactone

Spironolactone +/- SYNERGY Stent

Active Comparator group

Description:

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.

Treatment:

Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Drug: Colchicine-Placebo

Drug: Spironolactone

Colchicine +/- SYNERGY Stent

Active Comparator group

Description:

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.

Treatment:

Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Drug: Spironolactone-Placebo

Drug: Colchicine

Placebo +/- SYNERGY Stent

Placebo Comparator group

Description:

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.

Treatment:

Device: SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Drug: Spironolactone-Placebo

Drug: Colchicine-Placebo