The Use of Colchicine (an anti-inflammatory drug) in Prevention of Recurrent Stroke or heart attack after first Stroke; a randomised controlled trial

Phase 1

• Conditions: The prevention of recurrent stroke and coronary events (fatal and non- fatal) after ischaemic stroke and transient ischaemic attack (TIA) notcaused by cardiac embolism or other causes unrelated to atherosclerosis.; MedDRA version: 20.0Level: HLTClassification code 10044376Term: Transient cerebrovascular eventsSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: HLTClassification code 10008205Term: Cerebrovascular embolism and thrombosisSystem Organ Class: 100000004866; MedDRA version: 20.0Level: LLTClassification code 10023027Term: Ischaemic stroke NOSSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: LLTClassification code 10051615Term: Atherosclerotic cardiovascular diseaseSystem Organ Class: 100000004866; MedDRA version: 20.0Level: HLTClassification code 10007962Term: Central nervous system vascular disorders NECSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 20.0Level: HLGTClassification code 10007963Term: Central nervous system vascular disordersSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-004505-16-PT
• Lead Sponsor: niversity College Dublin

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-18
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 2623

Inclusion Criteria

To be eligible for inclusion, each subject must meet each of the following criteria at Screening Assessment and must continue to fulfil these criteria at enrolment into the trial (Baseline Visit).

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. Patient has had either;-
¿An ischaemic stroke without major disability (modified Rankin score 3 or less)
¿or
¿a high-risk TIA*

AND
A brain CT or MRI has excluded primary intracranial haemorrhage

AND
The stroke/TIA has occurred more than 72 hours before randomisation AND no more than 28 days prior to randomisation

- *High-risk TIA is defined as transient focal neurological symptoms of presumed vascular cause with, in addition, one or more of the following criteria:
(a)ABCD2 score 4 or more, with motor or speech symptoms (dysarthria or dysphasia)
(b)DWI hyperintensity on acute MRI
(c)Stenosis (lumen narrowing of 50% or greater on ultrasound, MRA, CTA, or invasive angiography) of the internal carotid, vertebral, middle cerebral, anterior cerebral, or basilar artery in the arterial territory consistent with symptoms

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. eGFR greater 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 875
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1748

Exclusion Criteria

Subjects are excluded from the study if any of the following criteria are met:

1.Stroke/TIA, probably caused by identified atrial fibrillation (permanent or paroxysmal), in the opinion of the treating physician.

2.Stroke/TIA probably caused by other identified cardiac source (intra-cardiac thrombus, endocarditis, metallic heart valve, low ejection fraction <30%),

3.Stroke/TIA caused by dissection, endocarditis, paradoxical embolism, drug use, venous thrombosis, carotid or cardiac surgery, hypercoagulability states, migraine, or inherited cerebrovascular disorders.

4.History of myopathy or myalgias with raised creatine kinase (CK) on statin therapy.

5.Blood dyscrasia (haemoglobin<10g/dL,platelet count <150 x109/L, white cell count <4 x109/L)

6.Impaired hepatic function (transaminases greater than twice upper limit of normal)

7.Concurrent treatment with colchicine contraindicated drugs:- 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.

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

11.Active malignancy, known hepatitis B or C, or HIV infection.

12.Impaired swallow preventing oral administration of Colchicine

13.History of poor medication compliance.

14.Unlikely to comply with study procedures due to severe or fatal comorbid illness or other factor (eg. inability to travel for follow up visits), in opinion of randomising physician.

15.Pregnancy, breast-feeding, or pre-menopausal woman

16.Patient concurrently participating in another clinical trial with an investigational drug or device, or use of investigational drug within 30 or 5 half-lives before the Screening visit (whichever is longer).

17.Known allergy or sensitivity to colchicine.

18.Requirement for colchicine therapy for treatment of acute gout, gout prevention, or other rheumatological disorder

19.Requirement for chronic daily immunosuppressants oral steroids, or non-steroidal anti-inflammatory drugs (NSAIDs)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified