Clinical trial NCT05159219: Colchicine for the Prevention of Vascular Events After an Acute Intracerebral Hemorrhage
Official title: A Vanguard, Double-blind, Randomized, Placebo-controlled, Phase 2 Pilot Study to Investigate Prevention of Cardiovascular Events with Oral Colchicine 0.5mg Once Daily Compared with Placebo in Participants with Spontaneous ICH and Established, or Risk Factors For, Atherosclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intracranial Hemorrhages
Keywords: Intracranial Hemorrhage
Colchicine
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2021-12-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Feasibility, double-blind, placebo-controlled randomized controlled trial (RCT)
Primary purpose: PREVENTION

Brief summary: The overall goal is to establish the safety and efficacy of colchicine in ICH patients for the prevention of major cardiovascular events and brain injury. Colchicine for the prevention of vascular events after an acute intracerebral hemorrhage (CoVasc-ICH) is a vanguard pilot trial designed to obtain the factual feasibility prerequisites essential for the planning, design, funding and execution of a subsequent phase III trial.


Eligibility criteria: Inclusion Criteria

Adult participants are eligible to be included in the study only if all of the following criteria apply:

Type of Participant and Disease Characteristics

1. Participants with documented spontaneous intraparenchymal hemorrhage within 48 hours of symptom onset (or last seen normal) and
2. Qualifying for at least one of the following categories:

   i. history of symptomatic coronary, peripheral and/or carotid artery disease (severe atherosclerotic vascular disease), or ii. visualized extracranial cervical/intracranial atherosclerotic disease causing any degree of stenosis/occlusion or presence of aortic arch plaque with maximum thickness ≥1 mm (moderate atherosclerotic vascular disease), or iii. two or more risk factors including: age 60 years or older, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease (eGFR: 15-50mL/min), history of ischemic stroke or current smoking (mild atherosclerotic vascular disease)

   Informed Consent
3. Capable of giving signed informed consent either independently, or by a legally authorized representative (LAR), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. Secondary causes of ICH (relating to trauma, macrovascular anomalies, neoplasms or bleeding diathesis)
2. Inflammatory bowel disease or chronic diarrhea
3. Cirrhosis or severe hepatic dysfunction
4. Renal insufficiency (eGFR \<15mL/min)

   Prior/Concomitant Therapy
5. Concurrent treatment with strong CYP3A4 inhibitors (atazanavir, clarithromycin, darunavir/ritonavir, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, tipranavir/ritonavir) or P-gp inhibitors (cyclosporine, ranolazine)
6. Known allergy or sensitivity to colchicine
7. Strong indication for colchicine where assignment to placebo is deemed unacceptable

   Other Exclusions
8. Pregnant or breast-feeding
9. Inability to adhere to study procedures
10. Estimated life expectancy less than 6 months at the time of enrollment
11. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g., employee or student of the investigational site)

Primary outcomes:
measure: Feasibility - Recruitment
timeFrame: From site activation until the end of recruitment (approximately 18 months)
Secondary outcomes:
measure: Feasibility - Refusal Rate
timeFrame: Exploratory, from first patient, first visit, until the common study end date (approximately 30 months)
measure: Feasibility - Retention Rate
timeFrame: At 6 months from randomization
measure: Feasibility - Medication Adherence
timeFrame: At 12 months from randomization
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary, Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton General Hospital, Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital, Kingston Health Sciences
state: Ontario
city: London
country: Canada
facility: London Health Science Centre, University Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montréal
country: Canada
facility: University of Montreal
state: Quebec
city: Saskatoon
country: Canada
facility: University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: Population Health Research Institute
name: Aristeidis Katsanos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Population Health Research Institute
name: Ashkan Shoamanesh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wilkinson CM, Katsanos AH, Sander NH, Kung TFC, Colbourne F, Shoamanesh A. Colchicine pre-treatment and post-treatment does not worsen bleeding or functional outcome after collagenase-induced intracerebral hemorrhage. PLoS One. 2022 Oct 18;17(10):e0276405. doi: 10.1371/journal.pone.0276405. eCollection 2022.