CONCISE COlchicine iN Circulating Inflammatory markers after StrokE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University College Dublin

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

completed 19 Nov 2024

Decision date (initial)

2024-02-16

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

HRB Stroke Clinical Trials Network Ireland (UCD)

External identifiers

EU CT number

2023-506967-33-00

ClinicalTrials.gov

NCT06062277

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Vascular inflammation drives risk of recurrent stroke, cardiac and vascular events in patients with atheroma and atherosclerosis. Anti inflammatory therapies, such as colchicine, can reduce the risk of further events but little is known whether colchicine also lowers serum biomarkers of inflammation.

Patients with a history of stroke or TIA and evidence of atherosclerosis at any site, defined as any of:
• intra-cranial or extra-cranial atheroma causing >30% stenosis or occlusion ipsilateral to the infarct
• Any atheroma proximal to the infarct in patients with cryptogenic stroke/ESUS in whom an alternative mechanism if not felt to be more likely in the opinion of the investigator
• Patient has a history of ischemic heart disease (IHD) or peripheral vascular disease (PVD), or has undergone
revascularisation procedures for IHD or PVD. and raised hsCRP ³2mg/L on baseline blood tests will be eligible for inclusion. Patients will be prescribed pleotropicanti-inflammatory colchicine 0.5mg daily for 30 days. A panel of
blood biomarkers will be drawn pre and post treatment.

The primary outcome will be calculated % change in hsCRP , IL-6 and other blood biomarkers of inflammation comparing before
treatment with after treatment.

Secondary objectives 1

1. The safety, tolerability, level of discontinuation and occurrence of adverse effects of colchicine will be assessed as secondary aims.

Conditions and MedDRA coding

Stroke

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Prior ischaemic stroke or ischaemic attack.
2. Living at home and independent (walking without the aid of another person, but may have some help for daily activities) without cognitive impairment causing limitation of daily function.
3. Medically-stable, and capable of participating in a research study and likely to follow study procedures, in the opinion of the study physician
4. Willing to provide informed consent
5. Age >18 years and <90 years
6. No history of chronic kidney disease and eGFR>50ml/min measured during screening phase
7. Serum hsCRP³2mg/L measured within 6 months of study entry
8. History of ischaemic stroke or TIA defined as a. Cerebral, spinal cord or retinal ischaemia based on neuropathological or neuroimaging evidence or clinical evidence of permanent injury. TIA= neurological dysfunction caused by focal cerebral or retinal ischaemia with clinical symptoms lasting <24 hours.
9. Presence of atheroma defined as: - intra-cranial or extra-cranial atheroma causing >30% stenosis or occlusion ipsilateral to the infarct AND/OR - Any atheroma proximal to the infarct in patients with cryptogenic stroke/ESUS in whom an alternative mechanism if not felt to be more likely in the opinion of the investigator AND/OR - Patient has a history of ischemic heart disease (IHD) or peripheral arterial disease (PAD), or has undergone revascularisation procedures for IHD or PAD.

Exclusion criteria 15

1. Stroke or TIA likely caused by identified atrial fibrillation (permanent or paroxysmal)
2. Stroke or TIA caused by other identified cardiac source (intracardiac thrombus, endocarditis, metallic heart value, low ejection fraction <30%)
3. History of myalgia with raised CK on statin therapy
4. Blood dyscrasia (Hb <10g/dl, Plt <150x1o^9/L, WCC <4x10^9/L) or other history of blood dyscrasia requiring follow up with haematology.
5. Impaired hepatic function (transaminases >twice ULN)
6. Concurrent treatment with contra-indicated drugs: CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, macrolides, ketoconazole, itraconazole, voriconazole, tolbutamide, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram) or P-gp inhibitors (cyclosporine) at screening.
7. Symptomatic peripheral neuropathy or progressive neuromuscular disease
8. Pre-existing inflammatory bowel disease, Crohn’s disease, Ulcerative colitis or chronic diarrhoea
9. Pre-existing inflammatory condition, intercurrent infection or other indication for regular anti-inflammatory therapies e.g., steroid, NSAIDs, immunosuppressants.
10. Requirement for colchicine therapy for acute gout or gout prevention or other rheumatological disorder.
11. Known sensitivity or allergy to colchicine.
12. Active malignancy or known Hepatitis B, C or HIV infection.
13. Dementia or cognitive impairment sufficient to impair independence in basic activities of daily living.
14. Women of childbearing potential. (Must be >24 months free of menstrual periods)
15. Patient concurrently enrolled in CONVINCE trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the difference in mean or median change in inflammatory biomarker panel from baseline to end of treatment

Secondary endpoints 1

1. The secondary endpoint is the proportion of patients at the end of treatment whose hsCRP level is suppressed below 2mg/L. Description of changes in inflammatory markers after treatment will also be a secondary analysis. Secondary endpoints will also include proportion of patients who discontinue colchicine treatment due to poor tolerability and prevalence of adverse events associated with colchicine treatment.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University College Dublin

Sponsor organisation

University College Dublin

Address

Catherine Mcauley Centre, 21 Nelson Street, Phibsborough 21 Nelson Street Phibsborough

City

Dublin 7

Postcode

DUB LIN7

Country

Ireland

Scientific contact point

Organisation

University College Dublin

Contact name

Prof Peter Kelly

Public contact point

Organisation

University College Dublin

Contact name

Prof Peter Kelly

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications