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

Stroke Clinical Trial

— CONVINCE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02898610
• Other study ID #: 2015-004505-16
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 12, 2016
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2023
• Source: University College Dublin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 3154
• Est. completion date: December 31, 2023
• Est. primary completion date: November 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Inflammation
• Ischemic Attack, Transient
• Stroke

Intervention

Drug:
• Colchicine

Locations

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

Sponsors (9)

Lead Sponsor	Collaborator
University College Dublin	Health Research Board, Ireland, Irish Heart Foundation, National University of Ireland, Galway, Ireland, Universitaire Ziekenhuizen KU Leuven, Universitat de Lleida, University of Athens, University of Edinburgh, University of Limerick

Countries where clinical trial is conducted

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

Outcome

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