Clinical trial NCT03048825: Colchicine and Spironolactone in Patients with MI / SYNERGY Stent Registry
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: ST Elevation Myocardial Infarction
Non ST Elevation Myocardial Infarction
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
name: Canadian Institutes of Health Research (CIHR)
First posted: 2017-02-09
Enrollment: 7264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Major Adverse Cardiac Events (MACE)
timeFrame: up to 1 year
measure: Composite of cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia driven revascularization
timeFrame: through study completion, an estimated average of 3 years
measure: Total composite events of cardiovascular death or new or worsening heart failure (co-primary 1)
timeFrame: through study completion, an estimated average of 3 years
measure: Composite of cardiovascular death, new or worsening heart failure, recurrent myocardial infarction, or stroke (co-primary 2)
timeFrame: through study completion, an estimated average of 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Central Cardiology
state: California
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Springfield
country: United States
facility: Prairie Education & Research Cooperative
state: Illinois
city: Munster
country: United States
facility: Community Hospital
state: Indiana
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Cincinnati
country: United States
facility: The Christ Hospital Lindner Research Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Bankstown
country: Australia
facility: Bankstown-Lidcombe hospital
state: New South Wales
city: Campbelltown
country: Australia
facility: SWSLHD - Campbelltown
state: New South Wales
city: Liverpool
country: Australia
facility: SWSLHD - Liverpool Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: New Westminster
country: Canada
facility: Fraser Clinical Trials
state: British Columbia
city: Victoria
country: Canada
facility: Victoria Heart Institute Foundation
state: British Columbia
city: Brampton
country: Canada
facility: William Osler Health
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Science Centre
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Newmarket
country: Canada
facility: York PCI Group Inc
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Saint Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough Cardiology Research Associates Inc.
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital, University Health Network
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - CHUS - Hôpital Fleurimont
state: Quebec
city: Regina
country: Canada
facility: PVRI - Regina General Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Quebec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie - ULAVAL
city: Brno
country: Czechia
facility: Czech Center University Hospital Brno
city: Brno
country: Czechia
facility: St. Anne´s University Hospital
city: Karlovy Vary
country: Czechia
facility: Karlovarska krajska nemocnice a.s.
city: Prague
country: Czechia
facility: University Hospital Královské Vinohrady
city: Mansoura
country: Egypt
facility: Mansoura University Hospital
state: Dakahlia
city: New Cairo
country: Egypt
facility: Kharga Specialized Hospital
state: Kharga
city: Alexandria
country: Egypt
facility: Alexandria University Hospital
city: Banī Suwayf
country: Egypt
facility: Beni Suef University Hospital
city: Cairo
country: Egypt
facility: Nasser Institute for Research and Treatment
city: Fayoum
country: Egypt
facility: Fayoum General Hospital
city: Fayoum
country: Egypt
facility: Tamia Central Hospital
city: Giza
country: Egypt
facility: National Heart Institute
city: Ismailia
country: Egypt
facility: Suez Canal University Hospital
city: Caen
country: France
facility: Centre Hospitalier Universitaire de Caen
state: Calvados
city: Nimes
country: France
facility: Centre Hospitalier Universitaire de Nimes
city: Paris
country: France
facility: Institut de Cardiologie de la Pitié-Salpêtrière
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Kecskemét
country: Hungary
facility: Bács-Kiskun County Hospital
city: Szeged
country: Hungary
facility: University of Szeged
city: Bharatpur
country: Nepal
facility: Chitwan Medical College Teaching Hospital
state: Bagmati Province/ State 3
city: Kathmandu
country: Nepal
facility: Shahid Gangalal National Heart Centre
state: Maharajgung
city: Kathmandu
country: Nepal
facility: Manmohan Cardiothoracic Vascular and Transplant Center
city: Almere
country: Netherlands
facility: Flevoziekenhuis
state: Flevoland
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen
state: Gelderland
city: Harderwijk
country: Netherlands
facility: St. Jansdal Ziekenhuis
state: Gelderland
city: Hilversum
country: Netherlands
facility: Tergooi Hospital
state: Noord Holland
city: Almelo
country: Netherlands
facility: ZiekenhuisGroepTwente (ZGT)
state: Overijssel
city: Gorinchem
country: Netherlands
facility: Beatrixziekenhuis
state: Zuid Holland
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis
state: Zuid Holland
city: 's-Hertogenbosch
country: Netherlands
facility: Bernhoven Ziekenhuis
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis
city: Den Haag
country: Netherlands
facility: Haga Hospital
city: Doetinchem
country: Netherlands
facility: Slingeland Ziekenhuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis
city: Ede
country: Netherlands
facility: Gelderse Vallei Ziekenhuis
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Hospital
city: Gouda
country: Netherlands
facility: Groene Hart Ziekenhuis Gouda
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Bitola
country: North Macedonia
facility: PHI Clinical Hospital "Dr. Trifun Panovski"
city: Skopje
country: North Macedonia
facility: University Clinic of Cardiology
city: Tetovo
country: North Macedonia
facility: Clinical Hospital Tetovo
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Belgrade
country: Serbia
facility: Institute for Cardiovascular Diseases Dedinje
city: Belgrade
country: Serbia
facility: University Medical Center Zvezdara
city: Sremska Kamenica
country: Serbia
facility: Institute of Cardiovascular Disease Vojvodina
city: Gijon
country: Spain
facility: Hospital de Cabueñes
state: Asturias
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias (HUCA)
state: Asturias
city: Palma
country: Spain
facility: Hospital Son Espases
state: Baleares
city: l'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Badalona
country: Spain
facility: Germans Trias i Pujol University Hospital
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Clínic Barcelona Hospital Universitario
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset NHS Foundation Trust
state: Dorset (county)
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: East Riding of Yorkshire (unitary authority)
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospital NHS Trust
state: East Sussex (county)
city: Stevenage
country: United Kingdom
facility: Lister Hospital
state: Hertfordshire (county)
city: Ashford
country: United Kingdom
facility: William Harvey Hospital -East Kent Hospitals University NHS Foundation Trust
state: Kent (county)
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: Norfolk (county)
city: Kettering
country: United Kingdom
facility: Kettering General Hospital
state: Northamptonshire (county)
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: Nottinghamshire (county)
city: Chertsey
country: United Kingdom
facility: Ashford & St Peter's Hospitals NHS Foundation Trust
state: Surrey (county)
city: Salisbury
country: United Kingdom
facility: Salisbury NHS Foundation Trust
state: Wiltshire (county)
city: London
country: United Kingdom
facility: St. George's Hospital NHS Foundation Trust
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: Population Health Research Institute
name: Sanjit S Jolly, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.