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

CONVINCE - (COlchicine for preventioN of Vascular Inflammation in Non- CardioEmbolic Stroke) - a Randomised Clinical Trial of Low-dose Colchicine for Secondary Prevention After Stroke

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

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Ischemic Attack, Transient
• Intervention / Treatment: Drug: Colchicine

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.

• Study Type: Interventional
• Enrollment (Actual): 3154
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Prof Peter Kelly; Email: isctn@ucd.ie
• Study Contact Backup: Name: Prof Sean Murphy; Email: isctn@ucd.ie

Study Locations

• Belgium
  • Antwerp, Belgium
    • Uza, Antwerpen
  • Brugge, Belgium
    • AZ Sint Jan
  • Brugge, Belgium
    • AZ St. Lucas, BRUGGE
  • Brussels, Belgium
    • UZ Brussel
  • Brussels, Belgium
    • UCL, Brussels
  • Gent, Belgium
    • UZ Gent
  • Kortrijk, Belgium
    • AZ Groeninge Kortrijk
  • Leuven, Belgium
    • UZ Leuven
  • Liège, Belgium
    • CHC Liège
  • Oostende, Belgium
    • AZ Damiaan, OOSTENDE
  • Roeselare, Belgium
    • AZ Delta, ROESELARE
• Canada
  • Calgary, Canada
    • Foothills Medical Centre, Calgary
  • Kingston, Canada
    • Kingston Hospital
  • Vancouver, Canada
    • Vancouver General Hospital
• Czechia
  • Brno, Czechia
    • St. Anne´s University Hospital
  • Jihlava, Czechia
    • Hospital Jihlava
• Denmark
  • Bispebjerg, Denmark
    • Bispebjerg Hospital
  • Glostrup, Denmark
    • Rigshospitalet Glostrup
  • Herlev, Denmark
    • Herlev Hospital
  • Hillerød, Denmark
    • Nordsjællands Hospital
• Estonia
  • Tallinn, Estonia
    • Astra Team Clinic
  • Tartu, Estonia
    • Tartu University Hospital
• Germany
  • Bad Neustadt An Der Saale, Germany
    • Rhön-Klinikum Campus Bad Neustadt
  • Berlin, Germany
    • Vivantes Humboldt-Klinikum
  • Berlin, Germany
    • Vivantes Auguste-Viktoria Klinikum
  • Berlin, Germany
    • Vivantes Klinikum Neukölln, Berlin
  • Bielefeld, Germany
    • Evangelisches Krankenhaus Bielefeld gGmbH
  • Bochum, Germany
    • St. Josef-Hospital Klinikum der Ruhr-Universität Bochum
  • Bonn, Germany
    • Universitätsklinikum Bonn
  • Buchholz, Germany
    • Krankenhaus Buchholz
  • Celle, Germany
    • Allgemeines Krankenhaus Celle
  • Dortmund, Germany
    • Klinikum Dortmund gGmbH
  • Essen, Germany
    • Universitätsklinikum Essen
  • Frankfurt, Germany
    • Frankfurt University Hospital
  • Fulda, Germany
    • Klinikum Fulda gAG, Universitätsmedizin Marburg-Campus Fulda
  • Gera, Germany
    • Srh Wald-Klinikum Gera Gmbh
  • Halle, Germany
    • Krakenhaus Martha Maria Halle Dolau
  • Hamburg, Germany
    • Universitätsklinikum Hamburg-Eppendorf
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Universitätsklinikum Heidelberg
  • Leipzig, Germany
    • Universitätsklinikum Leipzig AöR
  • Lohr, Germany
    • Klinikum Main-Spessart, Standort Krankenhaus Lohr
  • Lübeck, Germany
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Magdeburg, Germany
    • Universitätsklinikum Magdeburg A.ö.R.
  • München, Germany
    • Klinikum der Universität München
  • Rheine, Germany
    • Mediclin-Fachklinik Rhein/Ruhr
  • Sonneberg, Germany
    • Medinos Kliniken des Landkreises Sonneberg
  • Würzburg, Germany
    • Universitätsklinikum Würzburg
• Ireland
  • Cavan, Ireland
    • Cavan General Hospital
  • Cork, Ireland
    • Cork University Hospital
  • Dublin, Ireland
    • Beaumont Hospital
  • Dublin, Ireland
    • Mater Misericordiae University Hospital
  • Dublin, Ireland
    • St James's Hospital
  • Dublin, Ireland
    • St Vincent's University Hospital
  • Dublin, Ireland
    • Tallaght University Hospital
  • Dublin, Ireland
    • Connolly Hospital, Blanchardstown
  • Galway, Ireland
    • Galway University Hospital
  • Kilkenny, Ireland
    • St Lukes General Hospital
  • Limerick, Ireland
    • University Hospital Limerick
  • Louth, Ireland
    • Our Lady of Lourdes, Drogheda
  • Sligo, Ireland
    • Sligo University Hospital
  • Tipperary, Ireland
    • South Tipperary General Hospital, Clonmel
  • Waterford, Ireland
    • University Hospital Waterford
• Lithuania
  • Kaunas, Lithuania
    • Lithuanian University Hospital of Health Sciences Kaunos Klinikos
  • Vilnius, Lithuania
    • Vilnius University Hospital Santaros Clinics
  • Vilnius, Lithuania
    • Republican Vilnius University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center
  • Apeldoorn, Netherlands
    • Gelre Ziekenhuis Apeldoorn
  • Delft, Netherlands
    • Reinier de Graaf Hospital
  • Utrecht, Netherlands
    • University Medical Centre
• Poland
  • Gdańsk, Poland
    • Hospital Nicholas Copernicus
  • Końskie, Poland
    • Specialist Hospital of Saint Luke
  • Rokietnica, Poland
    • Medical University of Silesia Hospital No7
  • Warsaw, Poland
    • Institute of Psychiatry and Neurology
• Portugal
  • Coimbra, Portugal
    • Centro Hospitalar e Universitário de Coimbra
  • Lisboa, Portugal
    • Hospital Beatriz Angelo
  • Lisboa, Portugal
    • Hospital de Santa Maria, Centro Hospitalar Lisboa Norte
  • Lisboa, Portugal
    • Hospital Egas Moniz
  • Porto, Portugal
    • Hospital Universitario de Sao Jao
• Spain
  • Albacete, Spain
    • H. de Albacete
  • Barcelona, Spain
    • Hospital del Mar
  • Barcelona, Spain
    • Hospital de Sant Pau
  • Barcelona, Spain
    • Hospital Moises Broggi. Comprehensive Health Consortium
  • Coruna, Spain
    • Complejo Hospitalario Universitario A Coruna
  • Girona, Spain
    • H U. Josep Trueta, Girona
  • Lleida, Spain
    • Hospital Universitari Arnau de Vilanova de Lleida
  • Madrid, Spain
    • H. U. Ramón y Cajal, Madrid
  • Oviedo, Spain
    • Centro Medico de Asturias
  • Sabadell, Spain
    • H Parc Taulí de Sabadell
  • Sevilla, Spain
    • H U. Virgen del Rocío, Sevilla
  • Sevilla, Spain
    • Hospital Virgen Macarena Sevilla
  • Tarragona, Spain
    • H Joan XXIII, Tarragona
• Switzerland
  • Bern, Switzerland
    • University Hospital Bern
• United Kingdom
  • Aberystwyth, United Kingdom
    • Bronglais General Hospital
  • Aintree, United Kingdom
    • Aintree University Hospital
  • Airdrie, United Kingdom
    • Monklands Hospital
  • Antrim, United Kingdom
    • Antrim Area Hospital
  • Ashford, United Kingdom
    • William Harvey Hospital
  • Belfast, United Kingdom
    • Royal Victoria Hospital
  • Blackburn, United Kingdom
    • Royal Blackburn Hospital
  • Boston, United Kingdom
    • Pilgrim Hospital
  • Bournemouth, United Kingdom
    • Royal Bournemouth Hospital
  • Bury Saint Edmunds, United Kingdom
    • West Suffolk Hospital
  • Cambridge, United Kingdom
    • Addenbrookes Hospital
  • Canterbury, United Kingdom
    • Kent and Canterbury Hospital
  • Chester, United Kingdom
    • Countess of Chester Hospital
  • Chesterfield, United Kingdom
    • Chesterfield Royal Hospital
  • Chichester, United Kingdom
    • St Richards Hospital
  • Craigavon, United Kingdom
    • Craigavon Area Hospital
  • Cramlington, United Kingdom
    • Northumbria Specialist Emergency Care Hospital
  • Croydon, United Kingdom
    • Croydon University Hospital
  • Derby, United Kingdom
    • Royal Derby Hospital
  • Derry, United Kingdom
    • Altnagelvin Area Hospital
  • Durham, United Kingdom
    • North Durham University Hospital
  • Enniskillen, United Kingdom
    • South West Acute Hospital
  • Exeter, United Kingdom
    • Royal Devon & Exeter Hospital
  • Gateshead, United Kingdom
    • Queen Elizabeth Hospital Gateshead
  • Gillingham, United Kingdom
    • Medway Maritime Hospital
  • Glasgow, United Kingdom
    • Hairmyres Hospital
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital Glasgow
  • High Wycombe, United Kingdom
    • Wycombe Hospital
  • Inverness, United Kingdom
    • Raigmore Hospital
  • Kingston, United Kingdom
    • Kingston Hospital
  • Leicester, United Kingdom
    • Leicester Royal Infirmary
  • Lewisham, United Kingdom
    • University Hospital Lewisham
  • Lincoln, United Kingdom
    • Lincoln County Hospital
  • Liverpool, United Kingdom
    • Royal Liverpool University Hospital
  • London, United Kingdom
    • University College London Hospital
  • London, United Kingdom
    • Charing Cross Hospital
  • London, United Kingdom
    • St George's Hospital
  • London, United Kingdom
    • Royal London Hospital
  • London, United Kingdom
    • King's College Hospital
  • London, United Kingdom
    • St Thomas' Hospital
  • Luton, United Kingdom
    • Luton & Dunstable University Hospital
  • Maidstone, United Kingdom
    • Maidstone & District General Hospital
  • Margate, United Kingdom
    • Queen Elizabeth the Queen Mother Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich Hospital
  • Nottingham, United Kingdom
    • Nottingham City Hospital
  • Peterborough, United Kingdom
    • Peterborough Hospital
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Sheffield, United Kingdom
    • Royal Hallamshire Hospital
  • Southend, United Kingdom
    • Southend University Hospital
  • Stockport, United Kingdom
    • Stepping Hill Hospital
  • Stoke, United Kingdom
    • Royal Stoke University Hospital
  • Sunderland, United Kingdom
    • Sunderland Royal Hospital
  • Sutton In Ashfield, United Kingdom
    • King's Mill Hospital
  • Swindon, United Kingdom
    • Great Western Hospital
  • Telford, United Kingdom
    • Princess Royal Hospital
  • Truro, United Kingdom
    • Royal Cornwall Hospital
  • Whiston, United Kingdom
    • Whiston Hospital
  • Wolverhampton, United Kingdom
    • New Cross Hospital
  • Worthing, United Kingdom
    • Worthing Hospital
  • Yeovil, United Kingdom
    • Yeovil District Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Colchicine treatment; Colchicine 0.5mg/day plus usual care for 60 months	Drug: Colchicine
No Intervention: Usual Standard of care alone; Normal standard of care remains for these patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of non-fatal ischemic stroke	Any recurrence of non-fatal ischemic stroke	any time within 60 month
on-fatal Major Cardiac event	Non-fatal hospitalization for unstable angina, myocardial infarction, cardiac arrest	any time within 60 months
Vascular death	Fatal ischemic stroke, myocardial infarction, cardiac arrest	60 months

Collaborators and Investigators

• Sponsor: University College Dublin
• Collaborators: Universitaire Ziekenhuizen KU Leuven; National University of Ireland, Galway, Ireland; University of Athens; University of Edinburgh; University of Limerick; Health Research Board, Ireland; Universitat de Lleida; Irish Heart Foundation
• Investigators: Study Director: Prof Peter Kelly, Mater Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2016
• Primary Completion (Actual): November 21, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (Estimate): September 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Inflammation; Ischemic Attack, Transient; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 2015-004505-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A summary report of the trial will be provided to the Ethics Committees and relevant Regulatory Authority within as per national legal requirements in participating countries

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No