Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke

NCT ID: NCT02898610

Last Updated: 2025-03-13

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

3154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-12

Study Completion Date

2024-01-31

Brief Summary

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This study evaluates the use of Colchicine in adults over 40 years of age who have suffered an ischaemic stroke or transient ischaemic attack NOT caused by cardiac embolism or other defined causes. Patients will be randomised to 0.5 mg/day of Colchicine plus usual care, or to usual care alone.

To investigate the efficacy of low dose colchicine (0.5mg/day) plus usual care (defined as antiplatelet, lipid-lowering, antihypertensive treatment, and appropriate lifestyle advice) compared with usual care alone to prevent non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, hospitalization for unstable angina and vascular death after ischaemic stroke or transient ischaemic attack (TIA) not caused by cardiac embolism or other defined causes unrelated to atherosclerosis

Detailed Description

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Inflammation is a key pathophysiological contributor to unstable atherosclerotic plaque and thrombo-embolic events, stroke, myocardial infarction, and vascular death. Internationally, clinical trials are targeting atherosclerotic inflammation in patients with coronary disease using methotrexate, colchicine, and canukinumab.

Aims:

The primary aim is to compare low-dose colchicine (0.5mg/day) plus usual care, to usual care alone, to prevent non-fatal recurrent ischaemic stroke and coronary events and vascular death after non-severe, noncardioembolic TIA/stroke. Secondary objectives will investigate safety of low-dose colchicine, and efficacy for each component of the primary outcome, fatal and non-fatal events, disabling and non-disabling stroke, effect modification by prespecified subgroups, and impact on direct health care costs, adjusted for quality-adjusted life years.

Conditions

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Ischemic Attack, Transient Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Colchicine treatment

Colchicine 0.5mg/day plus usual care for 60 months

Group Type ACTIVE_COMPARATOR

Colchicine

Intervention Type DRUG

Usual Standard of care alone

Normal standard of care remains for these patients

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Colchicine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent consistent with ICH-GCP guidelines and local laws signed prior to all trial-related procedures.
2. Age 40 years or greater
3. Either,

* ischaemic stroke without major disability (modified Rankin score 3 or less)
* or high-risk TIA
4. Qualifying stroke/TIA probably caused by large artery stenosis, small artery occlusion (lacunar stroke), or cryptogenic embolism, with cardiac embolism or other defined stroke mechanism deemed unlikely in the opinion of the treating physician.
5. GFRgreater than or equal to 50 ml/min.
6. In the opinion of the treating physician, patient is medically-stable, capable of participating in a randomised trial, and willing to attend follow-up.

Exclusion Criteria

1. Cardio-embolic stroke/TIA, probably caused by identified atrial fibrillation (permanent or paroxysmal), in the opinion of the treating physician.
2. Cardio-embolic stroke/TIA probably caused by other identified cardiac source (intra-cardiac thrombus, endocarditis, metallic heart valve, low ejection fraction \<30%), in the opinion of the treating physician.
3. Stroke/TIA caused by dissection, endocarditis, paradoxical embolism, drug use, venous thrombosis, within 48 hours aftercarotid or cardiac surgery, hypercoagulability states, migraine, or inherited cerebrovascular disorders (eg. Fabry's disease, CADASIL), in the opinion of the treating physician.
4. History of myopathy or myalgias with raised creatine kinase (CK) on statin therapy.
5. Blood dyscrasia defined as anaemia (haemoglobin \<10g/dL), thrombocytopenia (platelet count \<150 x109/L) or leucopenia (white cell count \<4 x109/L) at randomisation.
6. Impaired hepatic function (transaminases greater than twice upper limit of normal) at randomisation.
7. Concurrent treatment with moderate or strong CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, other macrolide antibiotics, ketoconazole, itraconazole, voriconazole, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram) or P-gp inhibitors (cyclosporine) at randomisation.
8. Symptomatic peripheral neuropathy and pre-existing progressive neuromuscular disease
9. Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhoea.

9\. Dementia, sufficient to impair independence in basic activities of daily living.

10\. Active malignancy, known hepatitis B or C, or HIV infection prior to qualifying stroke/TIA.

11\. Impaired swallow preventing oral administration of study medication. 12. History of poor medication compliance. 13. Unlikely to comply with study procedures and follow-up visits due to severe or fatal comorbid illness or other factor (eg. inability to travel for follow up visits), in opinion of randomising physician.

14\. Pregnancy, breast-feeding, or pre-menopausal women 15. Patient concurrently participating in another clinical trial with an investigational drug or device, or use of investigational drug within 30 days or 5 half-lives before the Screening visit (whichever is longer) 16. Known allergy or sensitivity to colchicine.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Health Research Board, Ireland

OTHER

Sponsor Role collaborator

Irish Heart Foundation

OTHER

Sponsor Role collaborator

University of Limerick

OTHER

Sponsor Role collaborator

University of Edinburgh

OTHER

Sponsor Role collaborator

National University of Ireland, Galway, Ireland

OTHER

Sponsor Role collaborator

Universitat de Lleida

OTHER

Sponsor Role collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role collaborator

University College Dublin

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Prof Peter Kelly

Role: STUDY_DIRECTOR

Mater Hospital

Locations

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Uza, Antwerpen

Antwerp, , Belgium

Site Status

AZ Sint Jan

Bruges, , Belgium

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AZ St. Lucas, BRUGGE

Bruges, , Belgium

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UCL, Brussels

Brussels, , Belgium

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UZ Brussel

Brussels, , Belgium

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UZ Gent

Ghent, , Belgium

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AZ Groeninge Kortrijk

Kortrijk, , Belgium

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UZ Leuven

Leuven, , Belgium

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CHC Liege

Liège, , Belgium

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AZ Damiaan, OOSTENDE

Ostend, , Belgium

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AZ Delta, ROESELARE

Roeselare, , Belgium

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Foothills Medical Centre, Calgary

Calgary, , Canada

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Kingston Hospital

Kingston, , Canada

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Vancouver General Hospital

Vancouver, , Canada

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St. Anne´s University Hospital

Brno, , Czechia

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Hospital Jihlava

Jihlava, , Czechia

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Bispebjerg Hospital

Bispebjerg, , Denmark

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Rigshospitalet Glostrup

Glostrup Municipality, , Denmark

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Herlev Hospital

Herlev, , Denmark

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Nordsjællands Hospital

Hillerød, , Denmark

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Tartu University Hospital

Tartu, , Estonia

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Rhön-Klinikum Campus Bad Neustadt

Bad Neustadt an der Saale, , Germany

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Vivantes Auguste-Viktoria Klinikum

Berlin, , Germany

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Vivantes Humboldt-Klinikum

Berlin, , Germany

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Vivantes Klinikum Neukölln, Berlin

Berlin, , Germany

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St. Josef-Hospital Klinikum der Ruhr-Universität Bochum

Bochum, , Germany

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Universitätsklinikum Bonn

Bonn, , Germany

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Krankenhaus Buchholz

Buchholz, , Germany

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Klinikum Dortmund gGmbH

Dortmund, , Germany

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Universitätsklinikum Essen

Essen, , Germany

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Frankfurt University Hospital

Frankfurt, , Germany

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Klinikum Fulda gAG, Universitätsmedizin Marburg-Campus Fulda

Fulda, , Germany

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SRH Wald-Klinikum Gera GmbH

Gera, , Germany

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Krakenhaus Martha Maria Halle Dolau

Halle, , Germany

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Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

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Medizinische Hochschule Hannover

Hanover, , Germany

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Universitätsklinikum Heidelberg

Heidelberg, , Germany

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Universitätsklinikum Leipzig AöR

Leipzig, , Germany

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Klinikum Main-Spessart, Standort Krankenhaus Lohr

Lohr, , Germany

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Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, , Germany

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Klinikum der Universität München

München, , Germany

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Mediclin-Fachklinik Rhein/Ruhr

Rheine, , Germany

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Medinos Kliniken des Landkreises Sonneberg

Sonneberg, , Germany

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Universitätsklinikum Würzburg

Würzburg, , Germany

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Cavan General Hospital

Cavan, Cavan, Ireland

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Cork University Hospital

Cork, , Ireland

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Beaumont Hospital

Dublin, , Ireland

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Connolly Hospital, Blanchardstown

Dublin, , Ireland

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Mater Misericordiae University Hospital

Dublin, , Ireland

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St James's Hospital

Dublin, , Ireland

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St Vincent's University Hospital

Dublin, , Ireland

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Tallaght University Hospital

Dublin, , Ireland

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Galway University Hospital

Galway, , Ireland

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St Lukes General Hospital

Kilkenny, , Ireland

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University Hospital Limerick

Limerick, , Ireland

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Our Lady of Lourdes, Drogheda

Louth, , Ireland

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Sligo University Hospital

Sligo, , Ireland

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South Tipperary General Hospital, Clonmel

Tipperary, , Ireland

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University Hospital Waterford

Waterford, , Ireland

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Lithuanian University Hospital of Health Sciences Kaunos Klinikos

Kaunas, , Lithuania

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Vilnius University Hospital Santaros Clinics

Vilnius, , Lithuania

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Academic Medical Center

Amsterdam, , Netherlands

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Gelre Ziekenhuis Apeldoorn

Apeldoorn, , Netherlands

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Reinier de Graaf Hospital

Delft, , Netherlands

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Radboud University Medical Centre

Nijmegen, , Netherlands

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Hospital Nicholas Copernicus

Gdansk, , Poland

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Specialist Hospital of Saint Luke

Gmina Końskie, , Poland

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Medical University of Silesia Hospital No7

Rokietnica, , Poland

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Institute of Psychiatry and Neurology

Warsaw, , Poland

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Hospital de Santa Maria, Centro Hospitalar Lisboa Norte

Lisbon, , Portugal

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Hospital Egas Moniz

Lisbon, , Portugal

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Hospital Universitario de Sao Jao

Porto, , Portugal

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Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

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H. de Albacete

Albacete, , Spain

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Hospital de Sant Pau

Barcelona, , Spain

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Hospital del Mar

Barcelona, , Spain

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Hospital Moises Broggi. Comprehensive Health Consortium

Barcelona, , Spain

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H U. Josep Trueta, Girona

Girona, , Spain

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Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

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H. U. Ramón y Cajal, Madrid

Madrid, , Spain

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Centro Medico de Asturias

Oviedo, , Spain

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H Parc Taulí de Sabadell

Sabadell, , Spain

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H U. Virgen del Rocío, Sevilla

Seville, , Spain

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Hospital Virgen Macarena Sevilla

Seville, , Spain

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H Joan XXIII, Tarragona

Tarragona, , Spain

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University Hospital Bern

Bern, , Switzerland

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Bronglais General Hospital

Aberystwyth, , United Kingdom

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Aintree University Hospital

Aintree, , United Kingdom

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Monklands Hospital

Airdrie, , United Kingdom

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Antrim Area Hospital

Antrim, , United Kingdom

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William Harvey Hospital

Ashford, , United Kingdom

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Royal Victoria Hospital

Belfast, , United Kingdom

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Royal Blackburn Hospital

Blackburn, , United Kingdom

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Pilgrim Hospital

Boston, , United Kingdom

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Royal Bournemouth Hospital

Bournemouth, , United Kingdom

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West Suffolk Hospital

Bury St Edmunds, , United Kingdom

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Addenbrookes Hospital

Cambridge, , United Kingdom

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Kent and Canterbury Hospital

Canterbury, , United Kingdom

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Countess of Chester Hospital

Chester, , United Kingdom

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Chesterfield Royal Hospital

Chesterfield, , United Kingdom

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St Richards Hospital

Chichester, , United Kingdom

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Craigavon Area Hospital

Craigavon, , United Kingdom

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Northumbria Specialist Emergency Care Hospital

Cramlington, , United Kingdom

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Croydon University Hospital

Croydon, , United Kingdom

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Royal Derby Hospital

Derby, , United Kingdom

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North Durham University Hospital

Durham, , United Kingdom

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South West Acute Hospital

Enniskillen, , United Kingdom

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Royal Devon & Exeter Hospital

Exeter, , United Kingdom

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Queen Elizabeth Hospital Gateshead

Gateshead, , United Kingdom

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Medway Maritime Hospital

Gillingham, , United Kingdom

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Hairmyres Hospital

Glasgow, , United Kingdom

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Queen Elizabeth University Hospital Glasgow

Glasgow, , United Kingdom

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Wycombe Hospital

High Wycombe, , United Kingdom

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Raigmore Hospital

Inverness, , United Kingdom

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Kingston Hospital

Kingston, , United Kingdom

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Leicester Royal Infirmary

Leicester, , United Kingdom

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University Hospital Lewisham

Lewisham, , United Kingdom

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Lincoln County Hospital

Lincoln, , United Kingdom

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Royal Liverpool University Hospital

Liverpool, , United Kingdom

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Charing Cross Hospital

London, , United Kingdom

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King's College Hospital

London, , United Kingdom

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Royal London Hospital

London, , United Kingdom

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St George's Hospital

London, , United Kingdom

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St Thomas' Hospital

London, , United Kingdom

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University College London Hospital

London, , United Kingdom

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Altnagelvin Area Hospital

Londonderry, , United Kingdom

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Luton & Dunstable University Hospital

Luton, , United Kingdom

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Queen Elizabeth the Queen Mother Hospital

Margate, , United Kingdom

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Norfolk and Norwich Hospital

Norwich, , United Kingdom

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Nottingham City Hospital

Nottingham, , United Kingdom

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Peterborough Hospital

Peterborough, , United Kingdom

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Derriford Hospital

Plymouth, , United Kingdom

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Royal Hallamshire Hospital

Sheffield, , United Kingdom

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Southend University Hospital

Southend, , United Kingdom

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Stepping Hill Hospital

Stockport, , United Kingdom

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Royal Stoke University Hospital

Stoke, , United Kingdom

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Sunderland Royal Hospital

Sunderland, , United Kingdom

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King's Mill Hospital

Sutton in Ashfield, , United Kingdom

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Great Western Hospital

Swindon, , United Kingdom

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Princess Royal Hospital

Telford, , United Kingdom

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Royal Cornwall Hospital

Truro, , United Kingdom

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Whiston Hospital

Whiston, , United Kingdom

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New Cross Hospital

Wolverhampton, , United Kingdom

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Worthing Hospital

Worthing, , United Kingdom

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Yeovil District Hospital

Yeovil, , United Kingdom

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Countries

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Belgium Canada Czechia Denmark Estonia Germany Ireland Lithuania Netherlands Poland Portugal Spain Switzerland United Kingdom

References

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Kelly P, Lemmens R, Weimar C, Walsh C, Purroy F, Barber M, Collins R, Cronin S, Czlonkowska A, Desfontaines P, De Pauw A, Evans NR, Fischer U, Fonseca C, Forbes J, Hill MD, Jatuzis D, Korv J, Kraft P, Kruuse C, Lynch C, McCabe D, Mikulik R, Murphy S, Nederkoorn P, O'Donnell M, Sandercock P, Schroeder B, Shim G, Tobin K, Williams DJ, Price C. Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial. Lancet. 2024 Jul 13;404(10448):125-133. doi: 10.1016/S0140-6736(24)00968-1. Epub 2024 Jun 7.

Reference Type BACKGROUND
PMID: 38857611 (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)

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)

Other Identifiers

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2015-004505-16

Identifier Type: -

Identifier Source: org_study_id

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