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

Coronary Artery Disease Clinical Trial

— COL BE PCI  

Official title:

Colchicine in Belgium in Patients With Coronary Artery Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06095765
• Other study ID #: ONZ-2023-0237
• Secondary ID: KCE-INV-21-13242
• Status: Recruiting
• Phase: Phase 3
• Start date: January 29, 2024
• Est. completion date: March 1, 2028

Study information

• Verified date: March 2024
• Source: AZ Sint-Jan AV
• Contact: Lisette Van Hove
• Phone: +32 50 45 39 07
• Email: Lisette.VanHove[@]azsintjan.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2770
• Est. completion date: March 1, 2028
• Est. primary completion date: November 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Colchicine 0.5 MG Oral Tablet
Oral intake of 0.5 mg colchicine once daily
• Placebo
Oral intake of matching placebo once daily

Locations

Country	Name	City	State
Belgium	Algemeen Stedelijk Ziekenhuis Campus Aalst	Aalst
Belgium	Het Ziekenhuisnetwerk Antwerpen	Antwerpen
Belgium	Universitair Ziekenhuis Antwerpen	Antwerpen
Belgium	Imelda	Bonheiden
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	Humani Charleroi	Charleroi
Belgium	Ziekenhuis Oost Limburg	Genk
Belgium	AZ Sint-Lucas & Volkskliniek	Gent
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Jessa Ziekenhuis	Hasselt
Belgium	Algemeen Ziekenhuis Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	Centre Hospitalier Regional De La Citadelle	Liège
Belgium	Clinique Saint-Luc Bouge	Namur
Belgium	AZ Delta	Roeselare
Belgium	AZ Turnhout	Turnhout
Belgium	Cliniques Universitaires Saint-Luc	Woluwe-Saint-Lambert
Belgium	UCL Mont-Godinne	Yvoir

Sponsors (3)

Lead Sponsor	Collaborator
AZ Sint-Jan AV	Belgium Health Care Knowledge Centre, University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

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. — View Citation

Fiolet ATL, Opstal TSJ, Mosterd A, Eikelboom JW, Jolly SS, Keech AC, Kelly P, Tong DC, Layland J, Nidorf SM, Thompson PL, Budgeon C, Tijssen JGP, Cornel JH. Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials. Eur Heart J. 2021 Jul 21;42(28):2765-2775. doi: 10.1093/eurheartj/ehab115. Erratum In: Eur Heart J. 2021 May 23;: — View 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. — View Citation

Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847. doi: 10.1056/NEJMoa2021372. Epub 2020 Aug 31. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from randomisation to year 1 (and year 2 if available): in hsCRP as a measure of Inflammation.	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: (high sensitivity) C-reactive protein (mg/dl)	24 months
Other	Change from randomisation to year 1 (and year 2 if available): in white blood cell count as a measure of Inflammation.	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: white blood cell count (/µl)	24 months
Other	Change from randomisation to year 1 (and year 2 if available) in total cholesterol.	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: total cholesterol (mg/dl)	24 months
Other	Change from randomisation to year 1 (and year 2 if available) in low density lipoprotein.	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: low density lipoprotein (LDL) (mg/dl)	24 months
Other	Change from randomisation to year 1 (and year 2 if available) in high density lipoprotein .	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: high density lipoprotein (HDL) (mg/dl)	24 months
Other	Change from randomisation to year 1 (and year 2 if available) in triglycerides.	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: triglycerides (mg/dl)	24 months
Other	Change from randomisation to year 1 (and year 2 if available) in kidney function.	Change from randomisation to year 1 (and year 2 if available) in blood lab results from: estimated glomerular filtration rate (ml/min)	24 months
Primary	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	Time from randomisation to first occurrence of a composite of specific cardiovascular endpoints	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	44 months
Secondary	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
Secondary	Time from randomisation to first occurrence of breakdown components of primary endpoint and atherosclerosis-related diseases	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	44 months
Secondary	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
Secondary	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	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.	44 months
Secondary	Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Dyspnea	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.	44 months
Secondary	Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD): Depression.	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.	44 months
Secondary	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.	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).	44 months