Colchicine and Spironolactone in Patients with MI / SYNERGY Stent Registry
CLEAR SYNERGY
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
2 other identifiers
interventional
7,264
14 countries
109
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2018
Longer than P75 for phase_3
109 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 3, 2017
CompletedFirst Posted
Study publicly available on registry
February 9, 2017
CompletedStudy Start
First participant enrolled
February 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 9, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 9, 2024
CompletedOctober 15, 2024
October 1, 2024
6.5 years
February 3, 2017
October 10, 2024
Conditions
Outcome Measures
Primary Outcomes (4)
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, stroke, or unplanned ischemia driven revascularization
The first occurrence of cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia driven revascularization in the colchicine comparison
through study completion, an estimated average of 3 years
Total composite events of cardiovascular death or new or worsening heart failure (co-primary 1)
Total composite of cardiovascular death or new or worsening heart failure in the spironolactone comparison (co-primary 1)
through study completion, an estimated average of 3 years
Composite of cardiovascular death, new or worsening heart failure, recurrent myocardial infarction, or stroke (co-primary 2)
The first occurence of cardiovascular death, new or worsening heart failure, recurrent myocardial infarction, or stroke in the spironolactone comparison (co-primary 2)
through study completion, an estimated average of 3 years
Study Arms (4)
Colchicine + Spironolactone +/- SYNERGY Stent
ACTIVE COMPARATORColchicine 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
ACTIVE COMPARATORColchicine-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
ACTIVE COMPARATORColchicine 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
PLACEBO COMPARATORColchicine-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.
Interventions
Colchicine 0.5 mg once daily
Spironolactone 25 mg once daily
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.
Matching Colchicine-placebo once daily
Matching Spironolactone-Placebo once daily
Eligibility Criteria
You may qualify if:
- 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
- b) Patients with STEMI referred for PCI within 48 hours of symptom onset, not prospectively enrolled in SYNERGY stent registry
- 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
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Population Health Research Institutelead
- Boston Scientific Corporationcollaborator
- Canadian Institutes of Health Research (CIHR)collaborator
Study Sites (109)
Central Cardiology
Bakersfield, California, 93308, United States
Medstar Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
University of Illinois
Chicago, Illinois, 60612, United States
Prairie Education & Research Cooperative
Springfield, Illinois, 62769, United States
Community Hospital
Munster, Indiana, 46321, United States
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805, United States
New Mexico Heart Institute
Albuquerque, New Mexico, 87102, United States
NYU Langone Medical Center
New York, New York, 10016, United States
The Christ Hospital Lindner Research Center
Cincinnati, Ohio, 45219, United States
Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Bankstown-Lidcombe hospital
Bankstown, New South Wales, 2200, Australia
SWSLHD - Campbelltown
Campbelltown, New South Wales, 2560, Australia
SWSLHD - Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Peninsula Health
Frankston, Victoria, 3199, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, 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
Hamilton General Hospital
Hamilton, Ontario, L8L2X2, 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 Village, 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
Institut Universitaire de Cardiologie et de Pneumologie - ULAVAL
Québec, Quebec, G1V 4G5, Canada
CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont
Sherbrooke, Quebec, Canada
PVRI - Regina General Hospital
Regina, Saskatchewan, Canada
Royal University Hospital
Saskatoon, Saskatchewan, Canada
Czech Center University Hospital Brno
Brno, 625 00, Czechia
St. Anne´s University Hospital
Brno, 656 91, Czechia
Karlovarska krajska nemocnice a.s.
Karlovy Vary, 36225, Czechia
University Hospital Královské Vinohrady
Prague, 10000, Czechia
Mansoura University Hospital
Al Mansurah, Dakahlia Governorate, 35516, Egypt
Kharga Specialized Hospital
New Cairo, Kharga, 72738, Egypt
Fayoum General Hospital
Al Fayyum, 63511, Egypt
Tamia Central Hospital
Al Fayyum, 63711, Egypt
Alexandria University Hospital
Alexandria, 21568, Egypt
Beni Suef University Hospital
Banī Suwayf, 62511, Egypt
Nasser Institute for Research and Treatment
Cairo, 11576, Egypt
National Heart Institute
Giza, 12651, Egypt
Suez Canal University Hospital
Ismailia, 41522, Egypt
Centre Hospitalier Universitaire de Caen
Caen, Calvados, 14000, France
Centre Hospitalier Universitaire de Nimes
Nîmes, 30 000, France
Institut de Cardiologie de la Pitié-Salpêtrière
Paris, 75013, France
University of Debrecen
Debrecen, 4032, Hungary
Bács-Kiskun County Hospital
Kecskemét, 6000, Hungary
University of Szeged
Szeged, 6725, Hungary
Chitwan Medical College Teaching Hospital
Bharatpur, Bagmati Province/ State 3, 44200, Nepal
Shahid Gangalal National Heart Centre
Kathmandu, Maharajgung, 44600, Nepal
Manmohan Cardiothoracic Vascular and Transplant Center
Kathmandu, 44600, Nepal
Flevoziekenhuis
Almere Stad, Flevoland, 1315 RA, Netherlands
Gelre Ziekenhuizen
Apeldoorn, Gelderland, 7334DZ, Netherlands
St. Jansdal Ziekenhuis
Harderwijk, Gelderland, 3844 DG, Netherlands
Tergooi Hospital
Hilversum, North Holland, 1212VG, Netherlands
ZiekenhuisGroepTwente (ZGT)
Almelo, Overijssel, 7609PP, Netherlands
Beatrixziekenhuis
Gorinchem, South Holland, 4204 AA, Netherlands
Franciscus Gasthuis
Rotterdam, South Holland, 3045PM, Netherlands
Bernhoven Ziekenhuis
's-Hertogenbosch, 5223 GV, Netherlands
Rijnstate Ziekenhuis
Arnhem, 6815 AD, Netherlands
Slingeland Ziekenhuis
Doetinchem, 7009 BL, Netherlands
Albert Schweitzer ziekenhuis
Dordrecht, 3318 AT, Netherlands
Gelderse Vallei Ziekenhuis
Ede, 6716 RP, Netherlands
Admiraal de Ruyter Hospital
Goes, 4462 RA, Netherlands
Groene Hart Ziekenhuis Gouda
Gouda, 2803HH, Netherlands
Radboud UMC
Nijmegen, 6525 GA, Netherlands
Haga Hospital
The Hague, 2545AA, Netherlands
PHI Clinical Hospital "Dr. Trifun Panovski"
Bitola, 7000, North Macedonia
University Clinic of Cardiology
Skopje, 1000, North Macedonia
Clinical Hospital Tetovo
Tetovo, 1200, North Macedonia
Clinical Center of Serbia
Belgrade, 11000, Serbia
Institute for Cardiovascular Diseases Dedinje
Belgrade, 11000, Serbia
University Medical Center Zvezdara
Belgrade, 11000, Serbia
Institute of Cardiovascular Disease Vojvodina
Kamenitz, 21208, Serbia
Hospital Son Espases
Palma, Balearic Islands, 07120, Spain
Hospital del Mar
Barcelona, Barcelona, 08003, Spain
Clínic Barcelona Hospital Universitario
Barcelona, Barcelona, 08036, Spain
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital Universitario Virgen de las Nieves
Granada, Granada, 18014, Spain
Hospital de Cabueñes
Gijón, Principality of Asturias, 33394, Spain
Hospital Universitario Central de Asturias (HUCA)
Oviedo, Principality of Asturias, 33011, Spain
Germans Trias i Pujol University Hospital
Badalona, 08916, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Álvaro Cunqueiro
Vigo, 36312, Spain
Hôpitaux Universitaires de Genève
Geneva, 1205, Switzerland
Luzerner Kantonsspital
Lucerne, 6000, Switzerland
University Hospitals Dorset NHS Foundation Trust
Bournemouth, Dorset (county), BH7 7DW, United Kingdom
Castle Hill Hospital
Cottingham, East Riding of Yorkshire (unitary Authority), HU16 5JQ, United Kingdom
Brighton & Sussex University Hospital NHS Trust
Brighton, East Sussex (county), BN2 1ES, United Kingdom
Lister Hospital
Stevenage, Hertfordshire (county), SG14AB, United Kingdom
William Harvey Hospital -East Kent Hospitals University NHS Foundation Trust
Ashford, Kent (county), TN24 0LZ, United Kingdom
Norfolk and Norwich University Hospital
Norwich, Norfolk (county), NR4 7UY, United Kingdom
Kettering General Hospital
Kettering, Northamptonshire (county), NN16 8UZ, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire (county), NG5 1PB, United Kingdom
Ashford & St Peter's Hospitals NHS Foundation Trust
Chertsey, Surrey (county), KT16 0PZ, United Kingdom
Salisbury NHS Foundation Trust
Salisbury, Wiltshire (county), SP2 8BJ, United Kingdom
St. George's Hospital NHS Foundation Trust
London, SW17OQT, United Kingdom
The James Cook University Hospital
Middlesbrough, TS4 3BW, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S57AU, United Kingdom
Related Publications (7)
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.
PMID: 39555823DERIVEDJolly 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.
PMID: 39555814DERIVEDd'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.
PMID: 38936755DERIVEDAkl 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.
PMID: 38505729DERIVEDGranger 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.
PMID: 36526898DERIVEDBouabdallaoui 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.
PMID: 34269908DERIVEDSilvis 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.
PMID: 32648087DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sanjit S Jolly, MD
Population Health Research Institute
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- double-dummy masking of colchicine and spironolactone in 2x2 factorial
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 3, 2017
First Posted
February 9, 2017
Study Start
February 1, 2018
Primary Completion
August 9, 2024
Study Completion
August 9, 2024
Last Updated
October 15, 2024
Record last verified: 2024-10