Riisc

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

17 May 2023 → ongoing

Decision date (initial)

2024-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513669-38-00

EudraCT number

2022-001838-11

ClinicalTrials.gov

NCT05476991

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the long-term efficacy of low dose colchicine on the reduction of a composite primary outcome cluster of recurrent major vascular events

Secondary objectives 1

1. To evaluate the efficacy on each individual component of composite outcome, and total death

Conditions and MedDRA coding

Stroke, Ischemic, TIA, Cardiac Disease, Atherosclerosis, Myocardial Infarction, Coronary Syndrome, Cerebral Infarction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Cerebral infarction (CI) proven by neuro-imaging (MRI or head-CT), immediately once the neurologic deficit is stabilized (investigator judgement) if the patient was on antiplatelet agent monotherapy after the qualifying event, or after 21 days if the patient was on clopidogrel plus aspirin after the qualifying event, or after 21 to 30 days if the patient was on ticagrelor plus aspirin after the qualifying event (TIA with documented ischemic lesion (MRI or CT) in the appropriate area corresponding to the symptoms will be considered CI, following the current definition)
2. AND documented atherosclerotic stenosis:- presence of carotid atherosclerotic stenosis (on the basis of carotid duplex, CTA, MRA, XRA – only the report will be required to document atherosclerotic disease) ipsilateral to the cerebral ischemic symptoms -OR presence of atherosclerotic stenosis of another cerebral artery (documented vertebral artery stenosis, basilar artery stenosis, other intracranial artery stenosis) ipsilateral to the ischemic area -OR presence of atherosclerotic disease of the aortic arch with a plaque ≥4mm in thickness with or without superimposed thrombus, OR a plaque <4 mm with a superimposed mobile thrombus (detected by transesophageal echocardiography or CT angiography)
3. OR with a history of symptomatic coronary artery disease
4. OR TIA lasting more 10 minutes or more (with motor symptoms or aphasia/dysarthria or visual defect), with total resolution and no brain lesion on neuro-imaging (TIA) If the patient was on antiplatelet agent monotherapy after the qualifying event, or after 21 days if the patient was on clopidogrel plus aspirin after the qualifying event, or after 21 to 30 days if the patient was on ticagrelor plus aspirin after the qualifying event - AND with ipsilateral carotid stenosis that was revascularized (endarterectomy or stenting) -OR with ipsilateral, potentially causal intracranial stenosis ≥70%
5. with no clear indication of colchicine treatment (gout, Mediterranean fever)
6. age equal or above 18
7. Rankin score less than ≤4 (ranges from 0 to 6, with 0 indicating no symptoms, 1 no disability, 2 to 3 needing some help with daily activities, 4 to 5 dependent or bedridden, and 6 death)
8. fully informed and signed inform consent
9. with social security number
10. medical examination before the participation to the research
11. Under contraception in case of childbearing potential (highly effective: 1) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation et 2) progestogen-only)
12. Pregnancy test for women of childbearing potential

Exclusion criteria 22

1. Hypersensitivity to colchicine or any of the excipients.
2. Anticipated concomitant oral or intravenous therapy with strong CYP3A4 inhibitors than cannot be stopped for the course of the course of this study
3. CI/TIA due to arterial dissection (as documented following the judgment of the investigator) or due to cardiac source of embolism without documented atherosclerotic disease (e.g., mitral stenosis or endomyocardial fibrosis, endocarditis) a patient with atrial fibrillation, or with a history of myocardial infarction, or with calcified aortic stenosis will be eligible if the above inclusion criteria are also met]
4. Symptomatic hemorrhagic stroke (the mere presence of asymptomatic cerebral hemosiderin deposits –so called “microbleedings”
5. Uncontrolled hypertension (investigator judgement)
6. Follow-up visit impossible or anticipated bad compliance.
7. Intercurrent disease that may interfere with evaluation of the primary end-point or that may prevent follow-up study visits
8. Anticipated pregnancy at time of enrollment in the study
9. Breastfeeding woman
10. Patients participating in another pharmaco therapeutic program with an experimental therapy that is known to affect colchicine therapy.
11. Leukopenia <3000UI/μl
12. Major digestive disorders (chronic diarrhea, inflammatory disease of the digestive tract as uncontrolled ulcerative colitis or active Crohn disease)
13. Patients with severe renal impairment (creatinine clearance < 30 ml/min)
14. Patients with severe hepatic impairment (Prothrombin Time < 50%),
15. Immunosuppression (all immunosuppressive treatments are forbidden, except for inhaled form corticosteroids),, medullary aplasia
16. Active chronic inflammatory disease with chronically elevated blood CRP/hsCRP levels (as in lupus or Horton's disease; patients with asthma or COPD are eligible),
17. Chronic active infection (e.g. tuberculosis). HIV is accepted if treatments taken do not interact with experimental treatments,
18. Evolving cancer with a life expectancy less than 3 years,
19. Hemodynamic instability (need for amines for more than 24 hours, circulatory assistance)
20. A recent severe sepsis (7 days) or all recent acute reaches
21. Chronic treatment (for more than 6 months) with corticosteroids (oral or intravenous) or NSAIDs (or repeated high-dose intake for less than 7 days).
22. Prohibited treatments: All treatments contraindicated during the use of colchicine for a few clinical cases, such as chronic inflammatory diseases and chronic infectious diseases, we will ask the coordinating investigator to validate the patient's eligibility.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Composite of: nonfatal ischemic stroke or nonfatal hemorrhagic stroke or undetermined stroke, nonfatal myocardial infarction, urgent coronary or carotid revascularization following new symptoms, and vascular death including sudden death during the study (from 36 to 60 months)

Secondary endpoints 13

1. Recurrent fatal and nonfatal ischemic stroke or urgent carotid revascularization following a new transient ischemic attack with negative neuro-imaging during the study
2. Recurrent fatal and nonfatal ischemic stroke during the study
3. Fatal and nonfatal myocardial infarction or urgent coronary revascularization following a new acute coronary syndrome during the study
4. Fatal and nonfatal myocardial infarction during the study
5. Vascular death during the study
6. Any stroke during the study
7. Any stroke or TIA during the study
8. Major coronary events (including MI) during the study
9. Any coronary end-points (MI, hospitalization for recurrent ACS, coronary revascularization procedure urgent or elective, fatal coronary event) during the study
10. Any death during the study
11. Fatal and non-fatal stroke with mRS>1
12. All revascularization procedures (coronary, carotid, peripheral) during the study
13. Carotid revascularization during the study

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pierre Amarenco

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Christine Pereira

Locations

1 EU/EEA country · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 23 files

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

Application history

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