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: 22.1Level: LLTClassification code 10023027Term: Ischaemic stroke NOSSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 21.1Level: 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; MedDRA version: 20.0Level: HLTClassification code 10008205Term: Cerebrovascular embolism and thrombosisSystem Organ Class: 100000004866; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-06
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 3154

Inclusion Criteria

To be eligible for inclusion, each subject must meet each of the following
criteria at the screening assessment and 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)(Clarification - retinal infarction due to retinal artery occlusion is
allowed )
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 cartoid, 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 1125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2029

Exclusion Criteria

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(intracardiac 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 ALT and/or AST 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,tolbutamide, 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
fatalcomorbid illness or other factor (eg. inability to travel for follow up
visits), in opinion of randomising physician.

15.Women of childbearing potential (WCBP), or pregnant or are
breastfeeding, are not eligible to participate in this study. (Clarification:
A woman of childbearing potential is a woman who:
- has not had surgery to remove the uterus and ovaries
- has had menstrual periods at any time in the preceding 24
consecutive months
- Menstrual periods interrupted due to cancer chemotherapy
treatment are considered WCBP as this may still allow conception.)
Pregnancy is considered highly unlikely during the trial because
women of childbearing potential are excluded. However, in the unlikely
event that a woman in the trial becomes pregnant, pregnancy
information will be collected.

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