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

Primary Purpose

ST Elevation Myocardial Infarction, Non ST Elevation Myocardial Infarction

Status
Active
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Colchicine
Spironolactone
SYNERGY Bioabsorbable Polymer Drug-Eluting Stent
Colchicine-Placebo
Spironolactone-Placebo
Sponsored by
Population Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ST Elevation Myocardial Infarction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

  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

Sites / Locations

  • Hamilton General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Colchicine + Spironolactone +/- SYNERGY Stent

Spironolactone +/- SYNERGY Stent

Colchicine +/- SYNERGY Stent

Placebo +/- SYNERGY Stent

Arm 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.

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 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-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.

Outcomes

Primary Outcome Measures

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
Composite of cardiovascular death, recurrent myocardial infarction, or stroke
The first occurrence of cardiovascular death, recurrent myocardial infarction, or stroke in the colchicine comparison
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

Secondary Outcome Measures

Full Information

First Posted
February 3, 2017
Last Updated
June 1, 2023
Sponsor
Population Health Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR), Boston Scientific Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT03048825
Brief Title
Colchicine and Spironolactone in Patients With MI / SYNERGY Stent Registry
Acronym
CLEAR SYNERGY
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 1, 2018 (Actual)
Primary Completion Date
May 30, 2024 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Population Health Research Institute
Collaborators
Canadian Institutes of Health Research (CIHR), Boston Scientific Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ST Elevation Myocardial Infarction, Non ST Elevation Myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Factorial Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double-dummy masking of colchicine and spironolactone in 2x2 factorial
Allocation
Randomized
Enrollment
7063 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Colchicine + Spironolactone +/- SYNERGY Stent
Arm Type
Experimental
Arm 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.
Arm Title
Spironolactone +/- SYNERGY Stent
Arm Type
Experimental
Arm 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.
Arm Title
Colchicine +/- SYNERGY Stent
Arm Type
Experimental
Arm 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.
Arm Title
Placebo +/- SYNERGY Stent
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Colchicine
Intervention Description
Colchicine 0.5 mg once daily
Intervention Type
Drug
Intervention Name(s)
Spironolactone
Intervention Description
Spironolactone 25 mg once daily
Intervention Type
Device
Intervention Name(s)
SYNERGY Bioabsorbable Polymer Drug-Eluting Stent
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Colchicine-Placebo
Intervention Description
Matching Colchicine-placebo once daily
Intervention Type
Drug
Intervention Name(s)
Spironolactone-Placebo
Intervention Description
Matching Spironolactone-Placebo once daily
Primary Outcome Measure Information:
Title
Major Adverse Cardiac Events (MACE)
Description
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
Time Frame
up to 1 year
Title
Composite of cardiovascular death, recurrent myocardial infarction, or stroke
Description
The first occurrence of cardiovascular death, recurrent myocardial infarction, or stroke in the colchicine comparison
Time Frame
through study completion, an estimated average of 2 years
Title
Composite of cardiovascular death or new or worsening heart failure
Description
The first occurrence of cardiovascular death or new or worsening heart failure in the spironolactone comparison
Time Frame
through study completion, an estimated average of 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sanjit S Jolly, MD
Organizational Affiliation
Population Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton General Hospital
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L2X2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34269908
Citation
Bouabdallaoui N, Tardif JC. Colchicine in the Management of Acute and Chronic Coronary Artery Disease. Curr Cardiol Rep. 2021 Jul 16;23(9):120. doi: 10.1007/s11886-021-01560-w.
Results Reference
derived
PubMed Identifier
32648087
Citation
Silvis MJM, Demkes EJ, Fiolet ATL, Dekker M, Bosch L, van Hout GPJ, Timmers L, de Kleijn DPV. Immunomodulation of the NLRP3 Inflammasome in Atherosclerosis, Coronary Artery Disease, and Acute Myocardial Infarction. J Cardiovasc Transl Res. 2021 Feb;14(1):23-34. doi: 10.1007/s12265-020-10049-w. Epub 2020 Jul 9.
Results Reference
derived

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Colchicine and Spironolactone in Patients With MI / SYNERGY Stent Registry

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