Clinical trial NCT06095765: Colchicine in Belgium in Patients With Coronary Artery Disease After Percutaneous Coronary Intervention
Official title: Colchicine in Belgium in Patients With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Coronary Artery Disease
Keywords: percutaneous coronary intervention
colchicine
Lead sponsor: AZ Sint-Jan AV
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: Belgium Health Care Knowledge Centre
First posted: 2023-10-23
Enrollment: 2770
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Colchicine versus placebo (1:1)
Primary purpose: PREVENTION

Brief summary: The main aim of this trial is to determine whether there are fewer cardiovascular events when patients with coronary artery disease take a low dose of colchicine of 0.5 mg daily on top of optimal standard treatment after treatment with PCI, compared with placebo in combination with optimal standard treatment. More specifically, we aim to investigate the benefits of a daily low dose of colchicine in patients with coronary artery disease after treatment with PCI, to confirm that a daily low dose of colchicine helps prevent additional incidents in coronary artery disease, and to identify a subgroup of patients with CAD who are at increased risk for cardiovascular events and could benefit most from colchicine.

Detailed description: This is a prospective, randomised, double-blind, multicenter, placebo-controlled phase III pragmatic superiority trial comparing colchicine 0.5 mg with placebo administered orally once-daily in up to 2770 participants with CAD treated with PCI. Participants will be randomised in a 1:1 ratio to receive either colchicine 0.5 mg or placebo as an adjunct to standard of care. The trial is event driven with trial closure being performed when the targeted number of 566 primary endpoint events has been reached.

Participants will be seen by the site staff 1 month after randomisation and thereafter every 12 months as per standard of care (SOC) and for IMP dispense and compliance, completing questionnaires and outcome event assessment until end of study. After the first month, a telephone visit will be scheduled every 6 months in between two standard of care on-site visits.

Eligibility criteria: Inclusion Criteria:

1. Age ≥45 years.
2. Coronary artery disease treated with PCI and optimal medical therapy, with at least one additional risk factor (based on SMART):

   1. Age ≥ year
   2. Diabetes mellitus, on treatment or new diagnosis with HbA1c ≥6.5%
   3. Current smoking
   4. Treated hypertension or lood pressure systolic ≥ 4 mmHg or diastolic ≥ mmHg
   5. Total cholesterol \>240 mg/dl untreated, or treated LDL \>70 mg/dl
   6. HDL \<40 mg/dl
   7. hsCRP \>2 mg/L AND chronic coronary syndrome (CCS)
   8. eGFR \<60 ml/min (MDRD)
   9. history of vascular disease:

      * CAD (PCI prior to index, CABG, MI)
      * stroke (ischemic or hemorrhagic)
      * carotid artery revascularisation
      * PAD (revascularisation, ABI \<0.85 at rest, amputation due to atherosclerotic disease)
      * AAA (repair, distal aortic anteroposterior diameter \>3.0cm)
3. Able to be enrolled/randomized between 2 hour and 5 days post PCI.
4. Written informed consent.

Exclusion Criteria:

1. Women who are pregnant, breastfeeding, or of childbearing potential who are not using an effective method of contraception. Or women who intend to donate oocytes.
2. Men who plan to father children during the study period or who are unwilling to use effective forms of contraception. Or men who intend to donate sperm.
3. Any contraindication or known intolerance to colchicine.
4. Chronic use of -or need for- colchicine.
5. Auto-immune disease or other condition requiring current or planned chronic systemic steroids, immunosuppressant or biologic drug targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab etc.).
6. Creatinine clearance \<30 mL/min/1.73 m2.
7. Cirrhosis Child-Pugh stadium B and C, or acute severe liver disease
8. Neuromuscular disease or non-transient CK levels \> 5 x ULN (unless due to MI).
9. History of cancer or lymphoproliferative disease within the last 3 years, other than successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, or localized cervix carcinoma in situ.
10. Current or planned use of any strong inhibitor of CYP3A4 or p-glycoprotein: macrolide antibiotics (clarithromycin, telithromycin), azole antifungal agents (ketoconazole, voriconazole, fluconazole, itraconazole), cyclosporine, HIV medication (ritonavir, lopinavir, tipranavir, atazanavir, darunavir, indinavir, saquinavir).
11. Chronic diarrhea, or inflammatory owel disease (Crohn's disease or ulcerative colitis).
12. Drug or alcohol abuse.
13. Planned cardiovascular intervention known on the day of screening.
14. Currently enrolled in another investigational trial.
15. Considered to be an unsuitable candidate by the investigator.

Primary outcomes:
measure: Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke, or coronary revascularisation.
timeFrame: 44 months
Secondary outcomes:
measure: Time from randomisation to first occurrence of a composite of specific cardiovascular endpoints
timeFrame: 44 months
measure: Time from randomisation to first occurrence of a composite of hard endpoints consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke
timeFrame: 44 months
measure: Time from randomisation to first occurrence of breakdown components of primary endpoint and atherosclerosis-related diseases
timeFrame: 44 months
measure: Time from randomisation to occurrence of first as well as recurrent endpoints consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke, or coronary revascularisation.
timeFrame: 44 months
measure: Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Angina Frequency scale
timeFrame: 44 months
measure: Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Dyspnea
timeFrame: 44 months
measure: Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Depression.
timeFrame: 44 months
measure: Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Health-related quality of life.
timeFrame: 44 months
Other outcomes:
measure: Change from randomisation to year 1 (and year 2 if available): in hsCRP as a measure of Inflammation.
timeFrame: 24 months
measure: Change from randomisation to year 1 (and year 2 if available): in white blood cell count as a measure of Inflammation.
timeFrame: 24 months
measure: Change from randomisation to year 1 (and year 2 if available) in total cholesterol.
timeFrame: 24 months
measure: Change from randomisation to year 1 (and year 2 if available) in low density lipoprotein.
timeFrame: 24 months
measure: Change from randomisation to year 1 (and year 2 if available) in high density lipoprotein .
timeFrame: 24 months
measure: Change from randomisation to year 1 (and year 2 if available) in triglycerides.
timeFrame: 24 months
measure: Change from randomisation to year 1 (and year 2 if available) in kidney function.
timeFrame: 24 months
Locations:
city: Aalst
country: Belgium
facility: Algemeen Stedelijk Ziekenhuis Campus Aalst
city: Antwerpen
country: Belgium
facility: Het Ziekenhuisnetwerk Antwerpen
city: Antwerpen
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Bonheiden
country: Belgium
facility: Imelda
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende AV
city: Charleroi
country: Belgium
facility: Humani Charleroi
city: Charleroi
country: Belgium
facility: Grand Hôpital de Charleroi
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
city: Gent
country: Belgium
facility: AZ Sint-Lucas & Volkskliniek
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Kortrijk
country: Belgium
facility: Algemeen Ziekenhuis Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Regional De La Citadelle
city: Namur
country: Belgium
facility: Clinique Saint-Luc Bouge
city: Roeselare
country: Belgium
facility: AZ Delta
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Yvoir
country: Belgium
facility: UCL Mont-Godinne
Study officials:
affiliation: ian.buysschaert@azsintjan.be
name: Ian Buysschaert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L'Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16.
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citation: Tong DC, Quinn S, Nasis A, Hiew C, Roberts-Thomson P, Adams H, Sriamareswaran R, Htun NM, Wilson W, Stub D, van Gaal W, Howes L, Collins N, Yong A, Bhindi R, Whitbourn R, Lee A, Hengel C, Asrress K, Freeman M, Amerena J, Wilson A, Layland J. Colchicine in Patients With Acute Coronary Syndrome: The Australian COPS Randomized Clinical Trial. Circulation. 2020 Nov 17;142(20):1890-1900. doi: 10.1161/CIRCULATIONAHA.120.050771. Epub 2020 Aug 29.
citation: Dorresteijn JA, Visseren FL, Wassink AM, Gondrie MJ, Steyerberg EW, Ridker PM, Cook NR, van der Graaf Y; SMART Study Group. Development and validation of a prediction rule for recurrent vascular events based on a cohort study of patients with arterial disease: the SMART risk score. Heart. 2013 Jun;99(12):866-72. doi: 10.1136/heartjnl-2013-303640. Epub 2013 Apr 10.
citation: Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013 Jan 29;61(4):404-410. doi: 10.1016/j.jacc.2012.10.027. Epub 2012 Dec 19.