Colchicine in Belgium in Patients With Coronary Artery Disease After Percutaneous Coronary Intervention

Phase 3

Recruiting

• Conditions: Coronary Artery Disease
• Interventions: Drug: Colchicine 0.5 MG Oral Tablet; Drug: Placebo

• Registration Number: NCT06095765
• Lead Sponsor: AZ Sint-Jan AV

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.

Study Timeline

• Study First Submitted: 2023-09-25
• Study First Submitted QC: 2023-10-17
• Study First Posted: 2023-10-23
• Study Start: 2024-01-29
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-07
• Last Update Posted: 2024-03-08
• Primary Completion: 2027-11-01
• Study Completion: 2028-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 2770

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine	Colchicine 0.5 MG Oral Tablet	Colchicine 0.5 mg oral once daily, in addition to SOC
Placebo	Placebo	Placebo oral once daily, in addition to SOC

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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): Health-related quality of life.	44 months	EuroQol five dimensions five level (EQ-5D-5L): consists of a descriptive system of self-perceived health status along fve dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and a visual analogue scale (VAS) which provides a self-rating of the general health status on a scale from 0 (worst imaginable state of health) to 100 (best imaginable state of health).

Trial Locations

Locations (19)

Het Ziekenhuisnetwerk Antwerpen; 🇧🇪 Antwerpen, Belgium

Universitair Ziekenhuis Antwerpen; 🇧🇪 Antwerpen, Belgium

AZ Sint-Lucas & Volkskliniek; 🇧🇪 Gent, Belgium

AZ Sint-Jan Brugge-Oostende AV; 🇧🇪 Brugge, Belgium

Algemeen Stedelijk Ziekenhuis Campus Aalst; 🇧🇪 Aalst, Belgium

Humani Charleroi; 🇧🇪 Charleroi, Belgium

Grand Hôpital de Charleroi; 🇧🇪 Charleroi, Belgium

Centre Hospitalier Regional De La Citadelle; 🇧🇪 Liège, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

Algemeen Ziekenhuis Groeninge; 🇧🇪 Kortrijk, Belgium

AZ Turnhout; 🇧🇪 Turnhout, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Woluwe-Saint-Lambert, Belgium

UCL Mont-Godinne; 🇧🇪 Yvoir, Belgium

AZ Delta; 🇧🇪 Roeselare, Belgium

Ziekenhuis Oost Limburg; 🇧🇪 Genk, Belgium

Clinique Saint-Luc Bouge; 🇧🇪 Namur, Belgium

Imelda; 🇧🇪 Bonheiden, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Jessa Ziekenhuis; 🇧🇪 Hasselt, Belgium