Colchicine and Spironolactone in Patients with MI / SYNERGY Stent Registry

NCT ID: NCT03048825

Last Updated: 2024-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

7264 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-01

Study Completion Date

2024-08-09

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).

Conditions

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ST Elevation Myocardial Infarction Non ST Elevation Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
double-dummy masking of colchicine and spironolactone in 2x2 factorial

Study Groups

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Colchicine + Spironolactone +/- SYNERGY 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.

Group Type ACTIVE_COMPARATOR

Colchicine

Intervention Type DRUG

Colchicine 0.5 mg once daily

Spironolactone

Intervention Type DRUG

Spironolactone 25 mg once daily

SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Intervention Type DEVICE

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.

Spironolactone +/- SYNERGY 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.

Group Type ACTIVE_COMPARATOR

Spironolactone

Intervention Type DRUG

Spironolactone 25 mg once daily

SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Intervention Type DEVICE

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.

Colchicine-Placebo

Intervention Type DRUG

Matching Colchicine-placebo once daily

Colchicine +/- SYNERGY 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.

Group Type ACTIVE_COMPARATOR

Colchicine

Intervention Type DRUG

Colchicine 0.5 mg once daily

SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Intervention Type DEVICE

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.

Spironolactone-Placebo

Intervention Type DRUG

Matching Spironolactone-Placebo once daily

Placebo +/- SYNERGY 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.

Group Type PLACEBO_COMPARATOR

SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

Intervention Type DEVICE

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.

Colchicine-Placebo

Intervention Type DRUG

Matching Colchicine-placebo once daily

Spironolactone-Placebo

Intervention Type DRUG

Matching Spironolactone-Placebo once daily

Interventions

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Colchicine

Colchicine 0.5 mg once daily

Intervention Type DRUG

Spironolactone

Spironolactone 25 mg once daily

Intervention Type DRUG

SYNERGY Bioabsorbable Polymer Drug-Eluting Stent

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 DEVICE

Colchicine-Placebo

Matching Colchicine-placebo once daily

Intervention Type DRUG

Spironolactone-Placebo

Matching Spironolactone-Placebo once daily

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boston Scientific Corporation

INDUSTRY

Sponsor Role collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role collaborator

Population Health Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sanjit S Jolly, MD

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

Locations

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Central Cardiology

Bakersfield, California, United States

Site Status

Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Prairie Education & Research Cooperative

Springfield, Illinois, United States

Site Status

Community Hospital

Munster, Indiana, United States

Site Status

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status

New Mexico Heart Institute

Albuquerque, New Mexico, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

The Christ Hospital Lindner Research Center

Cincinnati, Ohio, United States

Site Status

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Bankstown-Lidcombe hospital

Bankstown, New South Wales, Australia

Site Status

SWSLHD - Campbelltown

Campbelltown, New South Wales, Australia

Site Status

SWSLHD - Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Peninsula Health

Frankston, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

University of Alberta Hospital

Edmonton, Alberta, Canada

Site Status

Kelowna General Hospital

Kelowna, British Columbia, Canada

Site Status

Fraser Clinical Trials

New Westminster, British Columbia, Canada

Site Status

Victoria Heart Institute Foundation

Victoria, British Columbia, Canada

Site Status

William Osler Health

Brampton, Ontario, Canada

Site Status

Hamilton General Hospital

Hamilton, Ontario, Canada

Site Status

Kingston Health Science Centre

Kingston, Ontario, Canada

Site Status

St. Mary's General Hospital

Kitchener, Ontario, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

York PCI Group Inc

Newmarket, Ontario, Canada

Site Status

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Scarborough Cardiology Research Associates Inc.

Scarborough Village, Ontario, Canada

Site Status

Niagara Health System

St. Catharines, Ontario, Canada

Site Status

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

Toronto General Hospital, University Health Network

Toronto, Ontario, Canada

Site Status

Windsor Regional Hospital

Windsor, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Institut Universitaire de Cardiologie et de Pneumologie - ULAVAL

Québec, Quebec, Canada

Site Status

CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont

Sherbrooke, Quebec, Canada

Site Status

PVRI - Regina General Hospital

Regina, Saskatchewan, Canada

Site Status

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Site Status

Czech Center University Hospital Brno

Brno, , Czechia

Site Status

St. Anne´s University Hospital

Brno, , Czechia

Site Status

Karlovarska krajska nemocnice a.s.

Karlovy Vary, , Czechia

Site Status

University Hospital Královské Vinohrady

Prague, , Czechia

Site Status

Mansoura University Hospital

Al Mansurah, Dakahlia Governorate, Egypt

Site Status

Kharga Specialized Hospital

New Cairo, Kharga, Egypt

Site Status

Fayoum General Hospital

Al Fayyum, , Egypt

Site Status

Tamia Central Hospital

Al Fayyum, , Egypt

Site Status

Alexandria University Hospital

Alexandria, , Egypt

Site Status

Beni Suef University Hospital

Banī Suwayf, , Egypt

Site Status

Nasser Institute for Research and Treatment

Cairo, , Egypt

Site Status

National Heart Institute

Giza, , Egypt

Site Status

Suez Canal University Hospital

Ismailia, , Egypt

Site Status

Centre Hospitalier Universitaire de Caen

Caen, Calvados, France

Site Status

Centre Hospitalier Universitaire de Nimes

Nîmes, , France

Site Status

Institut de Cardiologie de la Pitié-Salpêtrière

Paris, , France

Site Status

University of Debrecen

Debrecen, , Hungary

Site Status

Bács-Kiskun County Hospital

Kecskemét, , Hungary

Site Status

University of Szeged

Szeged, , Hungary

Site Status

Chitwan Medical College Teaching Hospital

Bharatpur, Bagmati Province/ State 3, Nepal

Site Status

Shahid Gangalal National Heart Centre

Kathmandu, Maharajgung, Nepal

Site Status

Manmohan Cardiothoracic Vascular and Transplant Center

Kathmandu, , Nepal

Site Status

Flevoziekenhuis

Almere Stad, Flevoland, Netherlands

Site Status

Gelre Ziekenhuizen

Apeldoorn, Gelderland, Netherlands

Site Status

St. Jansdal Ziekenhuis

Harderwijk, Gelderland, Netherlands

Site Status

Tergooi Hospital

Hilversum, North Holland, Netherlands

Site Status

ZiekenhuisGroepTwente (ZGT)

Almelo, Overijssel, Netherlands

Site Status

Beatrixziekenhuis

Gorinchem, South Holland, Netherlands

Site Status

Franciscus Gasthuis

Rotterdam, South Holland, Netherlands

Site Status

Bernhoven Ziekenhuis

's-Hertogenbosch, , Netherlands

Site Status

Rijnstate Ziekenhuis

Arnhem, , Netherlands

Site Status

Slingeland Ziekenhuis

Doetinchem, , Netherlands

Site Status

Albert Schweitzer ziekenhuis

Dordrecht, , Netherlands

Site Status

Gelderse Vallei Ziekenhuis

Ede, , Netherlands

Site Status

Admiraal de Ruyter Hospital

Goes, , Netherlands

Site Status

Groene Hart Ziekenhuis Gouda

Gouda, , Netherlands

Site Status

Radboud UMC

Nijmegen, , Netherlands

Site Status

Haga Hospital

The Hague, , Netherlands

Site Status

PHI Clinical Hospital "Dr. Trifun Panovski"

Bitola, , North Macedonia

Site Status

University Clinic of Cardiology

Skopje, , North Macedonia

Site Status

Clinical Hospital Tetovo

Tetovo, , North Macedonia

Site Status

Clinical Center of Serbia

Belgrade, , Serbia

Site Status

Institute for Cardiovascular Diseases Dedinje

Belgrade, , Serbia

Site Status

University Medical Center Zvezdara

Belgrade, , Serbia

Site Status

Institute of Cardiovascular Disease Vojvodina

Kamenitz, , Serbia

Site Status

Hospital Son Espases

Palma, Balearic Islands, Spain

Site Status

Hospital del Mar

Barcelona, Barcelona, Spain

Site Status

Clínic Barcelona Hospital Universitario

Barcelona, Barcelona, Spain

Site Status

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

Hospital Universitario Virgen de las Nieves

Granada, Granada, Spain

Site Status

Hospital de Cabueñes

Gijón, Principality of Asturias, Spain

Site Status

Hospital Universitario Central de Asturias (HUCA)

Oviedo, Principality of Asturias, Spain

Site Status

Germans Trias i Pujol University Hospital

Badalona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Álvaro Cunqueiro

Vigo, , Spain

Site Status

Hôpitaux Universitaires de Genève

Geneva, , Switzerland

Site Status

Luzerner Kantonsspital

Lucerne, , Switzerland

Site Status

University Hospitals Dorset NHS Foundation Trust

Bournemouth, Dorset (county), United Kingdom

Site Status

Castle Hill Hospital

Cottingham, East Riding of Yorkshire (unitary Authority), United Kingdom

Site Status

Brighton & Sussex University Hospital NHS Trust

Brighton, East Sussex (county), United Kingdom

Site Status

Lister Hospital

Stevenage, Hertfordshire (county), United Kingdom

Site Status

William Harvey Hospital -East Kent Hospitals University NHS Foundation Trust

Ashford, Kent (county), United Kingdom

Site Status

Norfolk and Norwich University Hospital

Norwich, Norfolk (county), United Kingdom

Site Status

Kettering General Hospital

Kettering, Northamptonshire (county), United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire (county), United Kingdom

Site Status

Ashford & St Peter's Hospitals NHS Foundation Trust

Chertsey, Surrey (county), United Kingdom

Site Status

Salisbury NHS Foundation Trust

Salisbury, Wiltshire (county), United Kingdom

Site Status

St. George's Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

The James Cook University Hospital

Middlesbrough, , United Kingdom

Site Status

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, , United Kingdom

Site Status

Countries

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United States Australia Canada Czechia Egypt France Hungary Nepal Netherlands North Macedonia Serbia Spain Switzerland United Kingdom

References

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Jolly SS, d'Entremont MA, Lee SF, Mian R, Tyrwhitt J, Kedev S, Montalescot G, Cornel JH, Stankovic G, Moreno R, Storey RF, Henry TD, Mehta SR, Bossard M, Kala P, Layland J, Zafirovska B, Devereaux PJ, Eikelboom J, Cairns JA, Shah B, Sheth T, Sharma SK, Tarhuni W, Conen D, Tawadros S, Lavi S, Yusuf S; CLEAR Investigators. Colchicine in Acute Myocardial Infarction. N Engl J Med. 2025 Feb 13;392(7):633-642. doi: 10.1056/NEJMoa2405922. Epub 2024 Nov 17.

Reference Type DERIVED
PMID: 39555823 (View on PubMed)

Jolly SS, d'Entremont MA, Pitt B, Lee SF, Mian R, Tyrwhitt J, Kedev S, Montalescot G, Cornel JH, Stankovic G, Moreno R, Storey RF, Henry TD, Mehta SR, Bossard M, Kala P, Bhindi R, Zafirovska B, Devereaux PJ, Eikelboom J, Cairns JA, Natarajan MK, Schwalm JD, Sharma SK, Tarhuni W, Conen D, Tawadros S, Lavi S, Asani V, Topic D, Cantor WJ, Bertrand OF, Pourdjabbar A, Yusuf S; CLEAR investigators; CLEAR Investigators. Routine Spironolactone in Acute Myocardial Infarction. N Engl J Med. 2025 Feb 13;392(7):643-652. doi: 10.1056/NEJMoa2405923. Epub 2024 Nov 17.

Reference Type DERIVED
PMID: 39555814 (View on PubMed)

d'Entremont MA, Lee SF, Mian R, Kedev S, Montalescot G, Cornel JH, Stankovic G, Moreno R, Storey RF, Henry TD, Skuriat E, Tyrwhitt J, Mehta SR, Devereaux PJ, Eikelboom J, Cairns JA, Pitt B, Jolly SS. Design and rationale of the CLEAR SYNERGY (OASIS 9) trial: A 2x2 factorial randomized controlled trial of colchicine versus placebo and spironolactone vs placebo in patients with myocardial infarction. Am Heart J. 2024 Sep;275:173-182. doi: 10.1016/j.ahj.2024.06.007. Epub 2024 Jun 25.

Reference Type DERIVED
PMID: 38936755 (View on PubMed)

Akl E, Sahami N, Labos C, Genest J, Zgheib A, Piazza N, Jolly S. Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease. J Interv Cardiol. 2024 Mar 12;2024:8646351. doi: 10.1155/2024/8646351. eCollection 2024.

Reference Type DERIVED
PMID: 38505729 (View on PubMed)

Granger CB, Pocock SJ, Gersh BJ. The need for new clinical trials of old cardiovascular drugs. Nat Rev Cardiol. 2023 Feb;20(2):71-72. doi: 10.1038/s41569-022-00819-1. No abstract available.

Reference Type DERIVED
PMID: 36526898 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34269908 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32648087 (View on PubMed)

Other Identifiers

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OASIS-9

Identifier Type: OTHER

Identifier Source: secondary_id

CLSYN.1702

Identifier Type: -

Identifier Source: org_study_id

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