COL BE PCI: Colchicine in Belgium in Patients With Coronary Artery Disease After Percutaneous Coronary Intervention

Sponsor

AZ Sint-Jan AV (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06095765

Collaborator

University Hospital, Ghent (Other), Belgium Health Care Knowledge Centre (Other)

2,770

Enrollment

Locations

Arms

Anticipated Duration (Months)

145.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Colchicine 0.5 MG Oral Tablet Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2770 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Colchicine versus placebo (1:1)Colchicine versus placebo (1:1)

Masking:

Single (Outcomes Assessor)

Masking Description:

Double-blind

Primary Purpose:

Prevention

Official Title:

Colchicine in Belgium in Patients With Coronary Artery Disease

Anticipated Study Start Date :

Feb 1, 2024

Anticipated Primary Completion Date :

Mar 1, 2028

Anticipated Study Completion Date :

Mar 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Colchicine Colchicine 0.5 mg oral once daily, in addition to SOC	Drug: Colchicine 0.5 MG Oral Tablet Oral intake of 0.5 mg colchicine once daily
Placebo Comparator: Placebo Placebo oral once daily, in addition to SOC	Drug: Placebo Oral intake of matching placebo once daily

Arm

Intervention/Treatment

Experimental: Colchicine

Colchicine 0.5 mg oral once daily, in addition to SOC

Drug: Colchicine 0.5 MG Oral Tablet

Oral intake of 0.5 mg colchicine once daily

Placebo Comparator: Placebo

Placebo oral once daily, in addition to SOC

Drug: Placebo

Oral intake of matching placebo once daily

Outcome Measures

Primary Outcome Measures

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. [44 months]

Secondary Outcome Measures

Time from randomisation to first occurrence of a composite of specific cardiovascular endpoints [44 months]
Time from randomisation to first occurrence of a composite of: cardiovascular death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke or coronary revascularisation
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 [44 months]
Time from randomisation to first occurrence of breakdown components of primary endpoint and atherosclerosis-related diseases [44 months]
Time from randomisation to first occurrence of: all-cause death, cardiovascular death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke, coronary revascularisation, ischemia driven coronary revascularisation, stent thrombosis, peripheral artery revascularisation, transient ischemic attack (TIA) treated with carotid revascularisation
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. [44 months]
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 [44 months]
Change from randomisation to year 1 and to end of study of participants reported outcomes: Seattle Angina Questionnaire (SAQ) Angina Frequency Scale: categorizes angina (chest pain) frequency as following: daily angina (score = 0-30), weekly angina (score = 31-60), monthly angina (score = 61-99), and no angina (score = 100). Higher score indicates better outcome.
Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Dyspnea [44 months]
Change from randomisation to year 1 and to end of study of participants reported outcomes: Dyspnea (Rose Dyspnea Scale): a four-item questionnaire that assesses a patients' dyspnea level with common activities. One point is assigned to each activity associated with dyspnea. Scores range from 0 to 4. Higher score indicates worse outcome.
Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Depression. [44 months]
Change from randomisation to year 1 and to end of study of participants reported outcomes: Depression (Patient Health Questionnaire PHQ-2): inquires about the frequency of depressed mood and anhedonia. Scores range from 0 to 6. Higher score indicates worse outcome.

Other Outcome Measures

Change from randomisation to year 1 (and year 2 if available): in hsCRP as a measure of Inflammation. [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: (high sensitivity) C-reactive protein (mg/dl)
Change from randomisation to year 1 (and year 2 if available): in white blood cell count as a measure of Inflammation. [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: white blood cell count (/μl)
Change from randomisation to year 1 (and year 2 if available) in total cholesterol. [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: total cholesterol (mg/dl)
Change from randomisation to year 1 (and year 2 if available) in low density lipoprotein. [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: low density lipoprotein (LDL) (mg/dl)
Change from randomisation to year 1 (and year 2 if available) in high density lipoprotein . [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: high density lipoprotein (HDL) (mg/dl)
Change from randomisation to year 1 (and year 2 if available) in triglycerides. [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: triglycerides (mg/dl)
Change from randomisation to year 1 (and year 2 if available) in kidney function. [24 months]
Change from randomisation to year 1 (and year 2 if available) in blood lab results from: estimated glomerular filtration rate (ml/min)

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥45 years.
Coronary artery disease treated with PCI and optimal medical therapy, with at least one additional risk factor (based on SMART):
Age ≥ year
Diabetes mellitus, on treatment or new diagnosis with HbA1c ≥6.5%
Current smoking
Treated hypertension or lood pressure systolic ≥ 4 mmHg or diastolic ≥ mmHg
Total cholesterol >240 mg/dl untreated, or treated LDL >70 mg/dl
HDL <40 mg/dl
hsCRP >2 mg/dl AND chronic coronary syndrome (CCS)
eGFR <60 ml/min (MDRD)
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)

Able to be enrolled/randomized between 2 hour and 5 days post PCI.
Written informed consent.

Exclusion Criteria:

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.
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.
Any contraindication or known intolerance to colchicine.
Chronic use of -or need for- colchicine.
Auto-immune disease requiring current or planned chronic systemic steroids, immunosuppressant or biologic drug targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab etc.).
Creatinine clearance <30 mL/min/1.73 m2.
Cirrhosis Child-Pugh stadium B and C, or acute severe liver disease
Neuromuscular disease or non-transient CK levels > 5 x ULN (unless due to MI).
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.
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).
Chronic diarrhea, or inflammatory owel disease (Crohn's disease or ulcerative colitis).
Drug or alcohol abuse.
Planned coronary, carotid or peripheral revascularisation known on the day of screening.
Currently enrolled in another investigational trial.
Considered to be an unsuitable candidate by the investigator.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Algemeen Stedelijk Ziekenhuis Campus Aalst	Aalst	Belgium	9300
2	Het Ziekenhuisnetwerk Antwerpen	Antwerpen	Belgium	2020
3	Universitair Ziekenhuis Antwerpen	Antwerpen	Belgium	2650
4	Imelda	Bonheiden	Belgium	2820
5	AZ Sint-Jan Brugge-Oostende AV	Brugge	Belgium	8000
6	ISPPC CHU Charleroi	Charleroi	Belgium	6042
7	Grand Hôpital de Charleroi	Charleroi	Belgium	6060
8	Ziekenhuis Oost Limburg	Genk	Belgium	3600
9	AZ Sint-Lucas & Volkskliniek	Gent	Belgium	9000
10	Universitair Ziekenhuis Gent	Gent	Belgium	9000
11	Jessa Ziekenhuis	Hasselt	Belgium	3500
12	Algemeen Ziekenhuis Groeninge	Kortrijk	Belgium	8500
13	UZ Leuven	Leuven	Belgium	3000
14	Centre Hospitalier Regional De La Citadelle	Liège	Belgium	4000
15	Clinique Saint-Luc Bouge	Namur	Belgium	5004
16	AZ Delta	Roeselare	Belgium	8800
17	AZ Turnhout	Turnhout	Belgium	2300
18	Cliniques Universitaires Saint-Luc	Woluwe-Saint-Lambert	Belgium	1200
19	UCL Mont-Godinne	Yvoir	Belgium	5530