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
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)
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)
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

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

Bankstown-Lidcombe hospital; 🇦🇺 Bankstown, New South Wales, Australia

SWSLHD - Campbelltown; 🇦🇺 Campbelltown, New South Wales, Australia

SWSLHD - Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 St Leonards, New South Wales, Australia

Peninsula Health; 🇦🇺 Frankston, Victoria, Australia

Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada

Kelowna General Hospital; 🇨🇦 Kelowna, British Columbia, Canada

Fraser Clinical Trials; 🇨🇦 New Westminster, British Columbia, Canada

Victoria Heart Institute Foundation; 🇨🇦 Victoria, British Columbia, Canada

William Osler Health; 🇨🇦 Brampton, Ontario, Canada

Kingston Health Science Centre; 🇨🇦 Kingston, Ontario, Canada

St. Mary's General Hospital; 🇨🇦 Kitchener, Ontario, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

York PCI Group Inc; 🇨🇦 Newmarket, Ontario, Canada

University of Ottawa Heart Institute; 🇨🇦 Ottawa, Ontario, Canada

Niagara Health System; 🇨🇦 Saint Catharines, Ontario, Canada

Scarborough Cardiology Research Associates Inc.; 🇨🇦 Scarborough, Ontario, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

Toronto General Hospital, University Health Network; 🇨🇦 Toronto, Ontario, Canada

Windsor Regional Hospital; 🇨🇦 Windsor, Ontario, Canada

Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont; 🇨🇦 Sherbrooke, Quebec, Canada

PVRI - Regina General Hospital; 🇨🇦 Regina, Saskatchewan, Canada

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada

Institut Universitaire de Cardiologie et de Pneumologie - ULAVAL; 🇨🇦 Quebec, Canada

Czech Center University Hospital Brno; 🇨🇿 Brno, Czechia

St. Anne´s University Hospital; 🇨🇿 Brno, Czechia

Karlovarska krajska nemocnice a.s.; 🇨🇿 Karlovy Vary, Czechia

University Hospital Královské Vinohrady; 🇨🇿 Prague, Czechia

Mansoura University Hospital; 🇪🇬 Mansoura, Dakahlia, Egypt

Kharga Specialized Hospital; 🇪🇬 New Cairo, Kharga, Egypt

Alexandria University Hospital; 🇪🇬 Alexandria, Egypt

Beni Suef University Hospital; 🇪🇬 Banī Suwayf, Egypt

Nasser Institute for Research and Treatment; 🇪🇬 Cairo, Egypt

Fayoum General Hospital; 🇪🇬 Fayoum, Egypt

Tamia Central Hospital; 🇪🇬 Fayoum, Egypt

National Heart Institute; 🇪🇬 Giza, Egypt

Suez Canal University Hospital; 🇪🇬 Ismailia, Egypt

Centre Hospitalier Universitaire de Caen; 🇫🇷 Caen, Calvados, France

Centre Hospitalier Universitaire de Nimes; 🇫🇷 Nimes, France

Institut de Cardiologie de la Pitié-Salpêtrière; 🇫🇷 Paris, France

University of Debrecen; 🇭🇺 Debrecen, Hungary

Bács-Kiskun County Hospital; 🇭🇺 Kecskemét, Hungary

University of Szeged; 🇭🇺 Szeged, Hungary

Chitwan Medical College Teaching Hospital; 🇳🇵 Bharatpur, Bagmati Province/ State 3, Nepal

Shahid Gangalal National Heart Centre; 🇳🇵 Kathmandu, Maharajgung, Nepal

Manmohan Cardiothoracic Vascular and Transplant Center; 🇳🇵 Kathmandu, Nepal

Flevoziekenhuis; 🇳🇱 Almere, Flevoland, Netherlands

Gelre Ziekenhuizen; 🇳🇱 Apeldoorn, Gelderland, Netherlands

St. Jansdal Ziekenhuis; 🇳🇱 Harderwijk, Gelderland, Netherlands

Tergooi Hospital; 🇳🇱 Hilversum, Noord Holland, Netherlands

ZiekenhuisGroepTwente (ZGT); 🇳🇱 Almelo, Overijssel, Netherlands

Beatrixziekenhuis; 🇳🇱 Gorinchem, Zuid Holland, Netherlands

Franciscus Gasthuis; 🇳🇱 Rotterdam, Zuid Holland, Netherlands

Bernhoven Ziekenhuis; 🇳🇱 's-Hertogenbosch, Netherlands

Rijnstate Ziekenhuis; 🇳🇱 Arnhem, Netherlands

Haga Hospital; 🇳🇱 Den Haag, Netherlands

Slingeland Ziekenhuis; 🇳🇱 Doetinchem, Netherlands

Albert Schweitzer ziekenhuis; 🇳🇱 Dordrecht, Netherlands

Gelderse Vallei Ziekenhuis; 🇳🇱 Ede, Netherlands

Admiraal de Ruyter Hospital; 🇳🇱 Goes, Netherlands

Groene Hart Ziekenhuis Gouda; 🇳🇱 Gouda, Netherlands

Radboud UMC; 🇳🇱 Nijmegen, Netherlands

PHI Clinical Hospital "Dr. Trifun Panovski"; 🇲🇰 Bitola, North Macedonia

University Clinic of Cardiology; 🇲🇰 Skopje, North Macedonia

Clinical Hospital Tetovo; 🇲🇰 Tetovo, North Macedonia

Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Institute for Cardiovascular Diseases Dedinje; 🇷🇸 Belgrade, Serbia

University Medical Center Zvezdara; 🇷🇸 Belgrade, Serbia

Institute of Cardiovascular Disease Vojvodina; 🇷🇸 Sremska Kamenica, Serbia

Hospital de Cabueñes; 🇪🇸 Gijon, Asturias, Spain

Hospital Universitario Central de Asturias (HUCA); 🇪🇸 Oviedo, Asturias, Spain

Hospital Son Espases; 🇪🇸 Palma, Baleares, Spain

Hospital Universitario de Bellvitge; 🇪🇸 l'Hospitalet de Llobregat, Barcelona, Spain

Germans Trias i Pujol University Hospital; 🇪🇸 Badalona, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Clínic Barcelona Hospital Universitario; 🇪🇸 Barcelona, Spain

Hospital Universitario Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Álvaro Cunqueiro; 🇪🇸 Vigo, Spain

Hôpitaux Universitaires de Genève; 🇨🇭 Geneva, Switzerland

Luzerner Kantonsspital; 🇨🇭 Luzern, Switzerland

University Hospitals Dorset NHS Foundation Trust; 🇬🇧 Bournemouth, Dorset (county), United Kingdom

Castle Hill Hospital; 🇬🇧 Cottingham, East Riding of Yorkshire (unitary authority), United Kingdom

Brighton & Sussex University Hospital NHS Trust; 🇬🇧 Brighton, East Sussex (county), United Kingdom

Lister Hospital; 🇬🇧 Stevenage, Hertfordshire (county), United Kingdom

William Harvey Hospital -East Kent Hospitals University NHS Foundation Trust; 🇬🇧 Ashford, Kent (county), United Kingdom

Norfolk and Norwich University Hospital; 🇬🇧 Norwich, Norfolk (county), United Kingdom

Kettering General Hospital; 🇬🇧 Kettering, Northamptonshire (county), United Kingdom

Nottingham University Hospitals NHS Trust; 🇬🇧 Nottingham, Nottinghamshire (county), United Kingdom

Ashford & St Peter's Hospitals NHS Foundation Trust; 🇬🇧 Chertsey, Surrey (county), United Kingdom

Salisbury NHS Foundation Trust; 🇬🇧 Salisbury, Wiltshire (county), United Kingdom

St. George's Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom

The James Cook University Hospital; 🇬🇧 Middlesbrough, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust; 🇬🇧 Sheffield, United Kingdom

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada