Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke
- Registration Number
- NCT02898610
- Lead Sponsor
- University College Dublin
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3154
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Written informed consent consistent with ICH-GCP guidelines and local laws signed prior to all trial-related procedures.
-
Age 40 years or greater
-
Either,
- ischaemic stroke without major disability (modified Rankin score 3 or less)
- or high-risk TIA
-
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.
-
GFRgreater than or equal to 50 ml/min.
-
In the opinion of the treating physician, patient is medically-stable, capable of participating in a randomised trial, and willing to attend follow-up.
-
Cardio-embolic stroke/TIA, probably caused by identified atrial fibrillation (permanent or paroxysmal), in the opinion of the treating physician.
-
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.
-
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.
-
History of myopathy or myalgias with raised creatine kinase (CK) on statin therapy.
-
Blood dyscrasia defined as anaemia (haemoglobin <10g/dL), thrombocytopenia (platelet count <150 x109/L) or leucopenia (white cell count <4 x109/L) at randomisation.
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Impaired hepatic function (transaminases greater than twice upper limit of normal) at randomisation.
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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.
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Symptomatic peripheral neuropathy and pre-existing progressive neuromuscular disease
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Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhoea.
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Dementia, sufficient to impair independence in basic activities of daily living.
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Active malignancy, known hepatitis B or C, or HIV infection prior to qualifying stroke/TIA.
-
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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Colchicine treatment Colchicine Colchicine 0.5mg/day plus usual care for 60 months
- Primary Outcome Measures
Name Time Method on-fatal Major Cardiac event any time within 60 months Non-fatal hospitalization for unstable angina, myocardial infarction, cardiac arrest
Recurrence of non-fatal ischemic stroke any time within 60 month Any recurrence of non-fatal ischemic stroke
Vascular death 60 months Fatal ischemic stroke, myocardial infarction, cardiac arrest
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (144)
Uza, Antwerpen
🇧🇪Antwerp, Belgium
Vivantes Humboldt-Klinikum
🇩🇪Berlin, Germany
UCL, Brussels
🇧🇪Brussels, Belgium
AZ Groeninge Kortrijk
🇧🇪Kortrijk, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
AZ Damiaan, OOSTENDE
🇧🇪Oostende, Belgium
St. Josef-Hospital Klinikum der Ruhr-Universität Bochum
🇩🇪Bochum, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Krankenhaus Buchholz
🇩🇪Buchholz, Germany
Connolly Hospital, Blanchardstown
🇮🇪Dublin, Ireland
Vivantes Klinikum Neukölln, Berlin
🇩🇪Berlin, Germany
Klinikum Dortmund gGmbH
🇩🇪Dortmund, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
🇩🇪Lübeck, Germany
Mediclin-Fachklinik Rhein/Ruhr
🇩🇪Rheine, Germany
Medinos Kliniken des Landkreises Sonneberg
🇩🇪Sonneberg, Germany
Cork University Hospital
🇮🇪Cork, Ireland
St James's Hospital
🇮🇪Dublin, Ireland
Galway University Hospital
🇮🇪Galway, Ireland
Reinier de Graaf Hospital
🇳🇱Delft, Netherlands
Medical University of Silesia Hospital No7
🇵🇱Rokietnica, Poland
Royal Victoria Hospital
🇬🇧Belfast, United Kingdom
Royal Blackburn Hospital
🇬🇧Blackburn, United Kingdom
Pilgrim Hospital
🇬🇧Boston, United Kingdom
Croydon University Hospital
🇬🇧Croydon, United Kingdom
Altnagelvin Area Hospital
🇬🇧Derry, United Kingdom
North Durham University Hospital
🇬🇧Durham, United Kingdom
Royal Devon & Exeter Hospital
🇬🇧Exeter, United Kingdom
Medway Maritime Hospital
🇬🇧Gillingham, United Kingdom
Hairmyres Hospital
🇬🇧Glasgow, United Kingdom
Kingston Hospital
🇬🇧Kingston, United Kingdom
AZ Delta, ROESELARE
🇧🇪Roeselare, Belgium
Hospital Jihlava
🇨🇿Jihlava, Czechia
Rigshospitalet Glostrup
🇩🇰Glostrup, Denmark
Herlev Hospital
🇩🇰Herlev, Denmark
Nordsjællands Hospital
🇩🇰Hillerød, Denmark
Beaumont Hospital
🇮🇪Dublin, Ireland
Frankfurt University Hospital
🇩🇪Frankfurt, Germany
Klinikum Main-Spessart, Standort Krankenhaus Lohr
🇩🇪Lohr, Germany
Klinikum der Universität München
🇩🇪München, Germany
Krakenhaus Martha Maria Halle Dolau
🇩🇪Halle, Germany
Cavan General Hospital
🇮🇪Cavan, Ireland
Sligo University Hospital
🇮🇪Sligo, Ireland
South Tipperary General Hospital, Clonmel
🇮🇪Tipperary, Ireland
University Hospital Waterford
🇮🇪Waterford, Ireland
Lithuanian University Hospital of Health Sciences Kaunos Klinikos
🇱🇹Kaunas, Lithuania
Hospital de Sant Pau
🇪🇸Barcelona, Spain
Hospital Nicholas Copernicus
🇵🇱Gdańsk, Poland
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Universitari Arnau de Vilanova de Lleida
🇪🇸Lleida, Spain
University Hospital Bern
🇨🇭Bern, Switzerland
Whiston Hospital
🇬🇧Whiston, United Kingdom
Hospital de Santa Maria, Centro Hospitalar Lisboa Norte
🇵🇹Lisboa, Portugal
Hospital Moises Broggi. Comprehensive Health Consortium
🇪🇸Barcelona, Spain
Aintree University Hospital
🇬🇧Aintree, United Kingdom
Complejo Hospitalario Universitario A Coruña
🇪🇸Coruna, Spain
H Joan XXIII, Tarragona
🇪🇸Tarragona, Spain
Bronglais General Hospital
🇬🇧Aberystwyth, United Kingdom
Monklands Hospital
🇬🇧Airdrie, United Kingdom
Antrim Area Hospital
🇬🇧Antrim, United Kingdom
West Suffolk Hospital
🇬🇧Bury Saint Edmunds, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
William Harvey Hospital
🇬🇧Ashford, United Kingdom
Kent and Canterbury Hospital
🇬🇧Canterbury, United Kingdom
Chesterfield Royal Hospital
🇬🇧Chesterfield, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom
Countess of Chester Hospital
🇬🇧Chester, United Kingdom
St Richards Hospital
🇬🇧Chichester, United Kingdom
Northumbria Specialist Emergency Care Hospital
🇬🇧Cramlington, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Queen Elizabeth Hospital Gateshead
🇬🇧Gateshead, United Kingdom
Norfolk and Norwich Hospital
🇬🇧Norwich, United Kingdom
Raigmore Hospital
🇬🇧Inverness, United Kingdom
University Hospital Lewisham
🇬🇧Lewisham, United Kingdom
Queen Elizabeth the Queen Mother Hospital
🇬🇧Margate, United Kingdom
Queen Elizabeth University Hospital Glasgow
🇬🇧Glasgow, United Kingdom
St George's Hospital
🇬🇧London, United Kingdom
University College London Hospital
🇬🇧London, United Kingdom
Luton & Dunstable University Hospital
🇬🇧Luton, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Peterborough Hospital
🇬🇧Peterborough, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Southend University Hospital
🇬🇧Southend, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, United Kingdom
King's Mill Hospital
🇬🇧Sutton In Ashfield, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
Yeovil District Hospital
🇬🇧Yeovil, United Kingdom
Princess Royal Hospital
🇬🇧Telford, United Kingdom
H U. Josep Trueta, Girona
🇪🇸Girona, Spain
H. U. Ramón y Cajal, Madrid
🇪🇸Madrid, Spain
Hospital Virgen Macarena Sevilla
🇪🇸Sevilla, Spain
Centro Medico de Asturias
🇪🇸Oviedo, Spain
UZ Brussel
🇧🇪Brussels, Belgium
St. Anne´s University Hospital
🇨🇿Brno, Czechia
Bispebjerg Hospital
🇩🇰Bispebjerg, Denmark
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Our Lady of Lourdes, Drogheda
🇮🇪Louth, Ireland
St Vincent's University Hospital
🇮🇪Dublin, Ireland
St Lukes General Hospital
🇮🇪Kilkenny, Ireland
University Hospital Limerick
🇮🇪Limerick, Ireland
Vilnius University Hospital Santaros Clinics
🇱🇹Vilnius, Lithuania
Radboud University Medical Centre
🇳🇱Nijmegen, Netherlands
Hospital Egas Moniz
🇵🇹Lisboa, Portugal
Institute of Psychiatry and Neurology
🇵🇱Warsaw, Poland
H. de Albacete
🇪🇸Albacete, Spain
H U. Virgen del Rocío, Sevilla
🇪🇸Sevilla, Spain
H Parc Taulí de Sabadell
🇪🇸Sabadell, Spain
Royal Bournemouth Hospital
🇬🇧Bournemouth, United Kingdom
Craigavon Area Hospital
🇬🇧Craigavon, United Kingdom
South West Acute Hospital
🇬🇧Enniskillen, United Kingdom
Lincoln County Hospital
🇬🇧Lincoln, United Kingdom
Wycombe Hospital
🇬🇧High Wycombe, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Stepping Hill Hospital
🇬🇧Stockport, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke, United Kingdom
Great Western Hospital
🇬🇧Swindon, United Kingdom
Worthing Hospital
🇬🇧Worthing, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Vivantes Auguste-Viktoria Klinikum
🇩🇪Berlin, Germany
AZ St. Lucas, BRUGGE
🇧🇪Brugge, Belgium
CHC Liege
🇧🇪Liège, Belgium
Tartu University Hospital
🇪🇪Tartu, Estonia
Rhön-Klinikum Campus Bad Neustadt
🇩🇪Bad Neustadt An Der Saale, Germany
AZ Sint Jan
🇧🇪Brugge, Belgium
UZ Gent
🇧🇪Gent, Belgium
Vancouver General Hospital
🇨🇦Vancouver, Canada
Universitätsklinikum Essen
🇩🇪Essen, Germany
Klinikum Fulda gAG, Universitätsmedizin Marburg-Campus Fulda
🇩🇪Fulda, Germany
SRH Wald-Klinikum Gera GmbH
🇩🇪Gera, Germany
Universitätsklinikum Leipzig AöR
🇩🇪Leipzig, Germany
Foothills Medical Centre, Calgary
🇨🇦Calgary, Canada
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitätsklinikum Würzburg
🇩🇪Würzburg, Germany
Tallaght University Hospital
🇮🇪Dublin, Ireland
Academic Medical Center
🇳🇱Amsterdam, Netherlands
Gelre Ziekenhuis Apeldoorn
🇳🇱Apeldoorn, Netherlands
Mater Misericordiae University Hospital
🇮🇪Dublin, Ireland
Specialist Hospital of Saint Luke
🇵🇱Końskie, Poland
Hospital Universitario de Sao Jao
🇵🇹Porto, Portugal
St Thomas' Hospital
🇬🇧London, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom
Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom