Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
2,770
Countries
1
Sites
22
Coronary artery disease
To demonstrate that colchicine 0.5 mg daily reduces first occurrence of a composite endpoint consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation, whichever occurs first, in patients with CAD treated with PCI.
Key facts
- Sponsor
- Universitair Ziekenhuis Gent, Az St-Jan Brugge-Oostende A.V.
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 29 Jan 2024 → ongoing
- Decision date (initial)
- 2023-09-11
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Belgian Health Care Knowledge Centre (KCE)
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy
To demonstrate that colchicine 0.5 mg daily reduces first occurrence of a composite endpoint consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation, whichever occurs first, in patients with CAD treated with PCI.
Secondary objectives 4
- To provide additional support for the effectiveness of colchicine, by comparing the effect of colchicine 0.5 mg daily versus placebo when added to optimized medical therapy in patients with CAD treated with PCI with regards to: a. A specific cardiovascular composite endpoint consisting of: cardiovascular death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke, or coronary revascularisation
- To provide additional support for the effectiveness of colchicine, by comparing the effect of colchicine 0.5 mg daily versus placebo when added to optimized medical therapy in patients with CAD treated with PCI with regards to: b. A specific composite of hard endpoints consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction, non-fatal stroke
- To provide additional support for the effectiveness of colchicine, by comparing the effect of colchicine 0.5 mg daily versus placebo when added to optimized medical therapy in patients with CAD treated with PCI with regards to: c. Breakdown components of the primary outcome and atherosclerosis-related diseases
- To provide additional support for the effectiveness of colchicine, by comparing the effect of colchicine 0.5 mg daily versus placebo when added to optimized medical therapy in patients with CAD treated with PCI with regards to: d. Patients reported outcomes based on the International Consortium for Health Outcome Measurement (ICHOM) Standard Set for CAD
Conditions and MedDRA coding
Coronary artery disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10011078 | Coronary artery disease | 100000004849 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Randomised, double-blind, multicenter, placebo-controlled phase III pragmatic superiority trial 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. Adjudication of all primary and secondary endpoint events will be performed by blinded Event Adjudication Committee members, relying on original source data. Primary endpoint analysis will be performed according to the intent-to-treat principle.
|
Randomised Controlled | Double | [{"id":136382,"code":3,"name":"Monitor"},{"id":136386,"code":1,"name":"Subject"},{"id":136385,"code":4,"name":"Analyst"},{"id":136383,"code":2,"name":"Investigator"},{"id":136384,"code":5,"name":"Carer"}] | Colchicine: colchicine 0.5 mg administered orally once-daily Placebo: Placebo administered orally once-daily |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Age ≥45 years.
- Coronary artery disease treated with PCI and optimal medical therapy, with at least one additional risk factor (based on SMART): a. Age ≥ year b. Diabetes mellitus, on treatment or new diagnosis with HbA1c ≥6.5% c. Current smoking d. Treated hypertension or lood pressure systolic ≥ 4 mmHg or diastolic ≥ mmHg e. Total cholesterol >240 mg/dl untreated, or treated LDL >70 mg/dl f. HDL <40 mg/dl g. hsCRP >2 mg/dl AND chronic coronary syndrome (CCS) h. eGFR <60 ml/min (MDRD) i. 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 15
- 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.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is 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.
Secondary endpoints 3
- Time from randomisation to first occurrence of: ▪ a composite of specific cardiovascular endpoint consisting of: cardiovascular death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke or coronary revascularisation ▪ a composite of hard endpoints consisting of: all-cause death, spontaneous (non-procedural) non-fatal myocardial infarction (Type 1, 4B & C), non-fatal stroke ▪ Breakdown components of primary endpoint and atherosclerosis-related diseases
- 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.
- Change from randomisation to year 1 and to end of study of participants reported outcomes (based on ICHOM Standard Set for CAD) o Seattle Angina Questionnaire (SAQ) Angina Frequency Scale o Dyspnea (Rose Dyspnea Scale) o Depression (Patient Health Questionnaire PHQ-2)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Colchicine Tiofarma 500 microgram Tablets
PRD6141923 · Product
- Active substance
- Colchicine
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 0.5 mg milligram(s)
- Max total dose
- 671 mg milligram(s)
- Max treatment duration
- 44 Month(s)
- Authorisation status
- Authorised
- ATC code
- M04AC01 — COLCHICINE
- Marketing authorisation
- PL 17299/0003
- MA holder
- TIOFARMA BV
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Placebo Colchicine 0.5 mg tablets
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitair Ziekenhuis Gent
- Sponsor organisation
- Universitair Ziekenhuis Gent
- Address
- Corneel Heymanslaan 10
- City
- Gent
- Postcode
- 9000
- Country
- Belgium
Scientific contact point
- Organisation
- Universitair Ziekenhuis Gent
- Contact name
- Ian Buysschaert
Public contact point
- Organisation
- Universitair Ziekenhuis Gent
- Contact name
- Lisette Van Hove
Az St-Jan Brugge-Oostende A.V.
- Sponsor organisation
- Az St-Jan Brugge-Oostende A.V.
- Address
- Ruddershove 10
- City
- Brugge
- Postcode
- 8000
- Country
- Belgium
Scientific contact point
- Organisation
- Az St-Jan Brugge-Oostende A.V.
- Contact name
- Ian Buysschaert
Public contact point
- Organisation
- Az St-Jan Brugge-Oostende A.V.
- Contact name
- Lisette Van Hove
Sponsor responsibilities
- Article 77 implementation
- Universitair Ziekenhuis Gent
Locations
1 EU/EEA country · 22 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruiting | 2,770 | 22 |
| Rest of world | — | 0 | — |
Investigational sites
Antwerp University Hospital
Cardiology, Drie Eikenstraat 655, 2650, Edegem
Grand Hopital De Charleroi
Cardiology, Rue Marguerite Depasse 6, 6060, Charleroi
UCL Mont-Godinne
Cardiology, Avenue Dr-Gaston-Therasse 1, 5530, Yvoir
UZ Leuven
Cardiology, Herestraat 49, 3000, Leuven
Imelda
Cardiology, Imeldalaan 9, 2820, Bonheiden
Jessa Ziekenhuis
Cardiology, Stadsomvaart 11, 3500, Hasselt
Ziekenhuis Oost Limburg
Cardiology, Synaps Park 1, 3600, Genk
Algemeen Ziekenhuis Groeninge
Cardiology, President Kennedylaan 4, 8500, Kortrijk
Algemeen Stedelijk Ziekenhuis Campus Aalst
Cardiology, Merestraat 80, 9300, Aalst
Az Delta
Cardiology, Deltalaan 1, 8800, Roeselare
ISPPC CHU Charleroi
Cardiology, Chaussee De Bruxelles 140, 6042, Charleroi
Centre Hospitalier Regional De La Citadelle
Cardiology, Bld Du Douzieme-De-Ligne 1, 4000, Liege
Universitair Ziekenhuis Gent
Cardiology, Corneel Heymanslaan 10, 9000, Gent
Az St-Jan Brugge-Oostende A.V.
Cardiology, Ruddershove 10, 8000, Brugge
Az Maria Middelares Gent
Cardiology, Buitenring-Sint-Denijs 30, 9000, Gent
Vitaz
Cardiology, Moerlandstraat 1, 9100, Sint-Niklaas
AZ Turnhout
Cardiology, Rubensstraat 166, 2300, Turnhout
Cliniques Universitaires Saint-Luc
Cardiology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
Clinical Saint-Luc Bouge
Cardiology, Rue Saint-Luc 8, 5004, Namur
Het Ziekenhuisnetwerk Antwerpen
Cardiology, Lindendreef 1, 2020, Antwerp
Az Sint-Lucas & Volkskliniek
Cardiology, Groenebriel 1, 9000, Gent
UZ Brussel
Cardiology, Laarbeeklaan 101, 1090, Jette
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2024-01-29 | 2024-01-29 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF EN | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF FR | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF NL | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF sponsor statement_public | 1 |
| Subject information and informed consent form (for publication) | L2_Information leaflet-flyer for females ENG | 1.1 |
| Subject information and informed consent form (for publication) | L2_Information leaflet-flyer for females FR | 1.1 |
| Subject information and informed consent form (for publication) | L2_Information leaflet-flyer for females NL | 1.1 |
| Subject information and informed consent form (for publication) | L3_Informed consent procedure | 1 |
Application history
7 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-29 | Belgium | Acceptable 2023-09-06
|
2023-09-11 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-09-19 | Belgium | Acceptable | 2023-10-16 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-01-11 | Belgium | Acceptable | 2024-01-11 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2024-02-29 | Belgium | Acceptable | 2024-02-29 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-01-16 | Belgium | Acceptable | 2025-01-16 |
| 6 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-03-19 | Belgium | Acceptable | 2025-05-13 |
| 7 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-07-17 | Belgium | Acceptable | 2025-09-08 |