Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
2,500
Countries
1
Sites
19
Heart Failure
In an RCT of individuals with HF secondary to ischemic heart disease (IHD): 1) To examine the impact of colchicine compared to placebo on the composite outcome of CV death, a HF event (defined a HF hospitalization or urgent HF visit), or ischemic cardiovascular events (myocardial infarction, ischemic stroke, or arteria…
Key facts
- Sponsor
- Hamilton Health Sciences Corporation
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 23 Jan 2025 → ongoing
- Decision date (initial)
- 2024-10-30
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Canadian Institutes of Health Research (CIHR)
External identifiers
- EU CT number
- 2023-506675-96-00
- ClinicalTrials.gov
- NCT05873881
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
In an RCT of individuals with HF secondary to ischemic heart disease (IHD):
1) To examine the impact of colchicine compared to placebo on the composite outcome of CV death, a HF event (defined a HF hospitalization or urgent HF visit), or ischemic cardiovascular events (myocardial infarction, ischemic stroke, or arterial revascularization).
2) To examine the impact of thiamine on the composite outcome of CV death, or HF hospitalization.
Secondary objectives 2
- Colchicine: To determine whether colchicine reduces the risk of i) death from any cause, and ii) hospitalization from any cause.
- Thiamine: To determine whether thiamine reduces the risk of i) death from any cause, and ii) hospitalization from any cause.
Conditions and MedDRA coding
Heart Failure
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10019279 | Heart failure | 10007541 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Colchicine Compared to Placebo
|
Randomised Controlled | Double | [{"id":188900,"code":3,"name":"Monitor"},{"id":188898,"code":1,"name":"Subject"},{"id":188899,"code":2,"name":"Investigator"}] | Thaimine: Compared to no thiamine (control) in a prospective randomized open-label blinded endpoint (PROBE) design |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Age greater than or equal to 45 years
- Documented ischemic heart disease as the etiology of HF, which includes: a) a history of CAD, and b) determination of the cause of HF to be due to IHD based on local investigator assessment
- NYHA class II-IV symptoms
- Documented LVEF less than or equal to 45% within 1 year prior to enrollment
- Optimal medical treatment for HF as per local clinical practice
- Participants can be enrolled in the ambulatory or hospitalized setting
Exclusion criteria 10
- Female who is pregnant, breast-feeding or is considering becoming pregnant during the study
- Regular or required use colchicine or thiamine for other clinical indications
- History of allergic reaction to colchicine or to thiamine; or current or planned use of cyclosporine, verapamil, diltiazem, azole antifungal, macrolide antibiotic (except azithromycin), or HIV protease inhibitor
- Use of a ventricular assist device or prior heart transplant
- Severe valvular disease
- Coronary revascularization (coronary artery bypass graft surgery or percutaneous coronary intervention) within the 4 weeks prior to enrollment, or planned within the next 4 weeks.
- Chronic and severe renal dysfunction defined as eGFR < 15 mL/min/1.73m2 based on local laboratory measurement done within 6 months prior to run-in
- History of liver cirrhosis
- Active malignancy (excluding basal cell or treated squamous cell carcinoma of the skin) requiring treatment and with a life-expectancy of <2 years.
- Concurrent use of other experimental pharmacologic agents
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Colchicine arm: Composite of CV death, HF event, or ischemic CV event (defined as myocardial infarction, ischemic stroke, or arterial revascularization)
- Thiamine arm: Composite of CV death or HF event
Secondary endpoints 3
- All cause death, hospitalization
- Serious adverse events
- Side effects or adverse events resulting in study drug discontinuation
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Benerva 300 mg compresse gastroresistenti
PRD2755129 · Product
- Active substance
- Thiamine Hydrochloride
- Pharmaceutical form
- GASTRO-RESISTANT TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 300 mg milligram(s)
- Max treatment duration
- 48 Month(s)
- Authorisation status
- Authorised
- ATC code
- A11DA01 — THIAMINE (VIT B1)
- Marketing authorisation
- 004642031
- MA holder
- TEOFARMA S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
COLCHICINA LIRCA 0.5 mg compresse
PRD10219676 · Product
- Active substance
- Colchicine
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 0.5 mg milligram(s)
- Max total dose
- 0.5 mg milligram(s)
- Max treatment duration
- 48 Month(s)
- Authorisation status
- Authorised
- ATC code
- M04AC01 — COLCHICINE
- Marketing authorisation
- 009964040
- MA holder
- ACARPIA FARMACEUTICI S.R.L
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Placebo tablet matching Colchicina
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
Hamilton Health Sciences Corporation
- Sponsor organisation
- Hamilton Health Sciences Corporation
- Address
- 100 King Street West
- City
- Hamilton
- Postcode
- L8P 1A2
- Country
- Canada
Scientific contact point
- Organisation
- Hamilton Health Sciences Corporation
- Contact name
- Philip Joseph
Public contact point
- Organisation
- Hamilton Health Sciences Corporation
- Contact name
- Philip Joseph
Locations
1 EU/EEA country · 19 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 300 | 19 |
| Rest of world
India, Brazil, Colombia, Canada, Argentina
|
— | 2,200 | — |
Investigational sites
Azienda Socio Sanitaria Territoriale Della Valle Olona
U.O.C. DI CARDIOLOGIA, Via Arnaldo Da Brescia 1, 21052, Busto Arsizio
Alessandro Manzoni Hospital
S.C. DI CARDIOLOGIA, Via Dell' Eremo 9, 23900, Lecco
San Camillo Forlanini Hospital
UOC CARDIOLOGIA, Circonvallazione Gianicolense 87, 00152, Rome
Policlinico San Donato S.p.A.
CARDIOLOGIA RIABILITATIVA, Piazza Edmondo Malan 2, 20097, San Donato Milanese
Azienda Unita Sanitaria Locale Umbria 1
U.O. DI UTIC E CARDIOLOGIA, Via Guerriero Guerra 21, 06127, Perugia
Azienda Unita Sanitaria Locale Della Romagna
U.O. CARDIOLOGIA, Viale Luigi Settembrini 2, 47923, Rimini
Azienda Ospedaliero Universitaria Delle Marche
SOD CARDIOLOGIA OSPEDALIERA E UTIC, Via Conca 71, 60126, Ancona
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
SC CARDIOLOGIA 1, Piazza Oms 1, 24127, Bergamo
Azienda Sanitaria Locale Della Provincia Di Bari
CARDIOLOGIA-UTIC, Via Caposcardicchio Sn, 70132, Bari
ASST Grande Ospedale Metropolitano Niguarda
Cardiologia 2 - insufficienza cardiaca e trapianto, Piazza Dell'ospedale Maggiore 3, 20162, Milan
Azienda Ospedaliero Universitaria Ospedali Riuniti
S.C. DI CARDIOLOGIA UNIVERSITARIA-UTIC, Viale Luigi Pinto 1, 71122, Foggia
Azienda Ospedaliera Per L'Emergenza Cannizzaro
UOC CARDIOLOGIA, Via Messina 829, 95126, Catania
Azienda USL IRCCS Di Reggio Emilia
SOC CARDIOLOGIA OSPEDALIERA, Viale Risorgimento 80, 42123, Reggio Emilia
Azienda Ospedaliera S Giovanni Addolorata
UOC CARDIOLOGIA D'URGENZA E UTIC, Via Dell' Amba Aradam 9, 00184, Rome
ARNAS Civico Di Cristina Benfratelli
UOSD CARDIOLOGIA CLINICA TRATTAM. SCOMPENSO CARD., Piazza Nicola Leotta 4, 90127, Palermo
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
CARDIOLOGIA UTIC, Via Santa Sofia 78, 95123, Catania
Azienda Unita Sanitaria Locale Della Romagna
U.O. DI CARDIOLOGIA-UTIC, Viale Giovanni Ghirotti 286, 47521, Cesena
Azienda Sanitaria Locale Roma 1
CARDIOLOGIA CLINICA E RIABILITATIVA, Borgo Santo Spirito 3, 00193, Rome
Azienda Sanitaria Locale Roma 2
UOC CARDIOLOGIA - UTIC, Via Dei Monti Tiburtini 385, 00157, Rome
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 |
|---|---|---|---|---|---|
| Italy | 2025-01-23 | 2025-02-10 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-506675-96-00 | 4.0 |
| Protocol (for publication) | D1_Protocol 2023-506675-96-00_track | 3.1 |
| Protocol (for publication) | D1_Protocol 2023-506675-96-00_v1_track | 3.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements-ITA_NOT-public_Final | 1.1 |
| Subject information and informed consent form (for publication) | L1_ICF_Consent_Form_IT_Niguarda_public | 1.2 |
| Subject information and informed consent form (for publication) | L1_ICF_Consent_Form_IT_public | 1.2 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_DPIL_IT_public | 1.1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_GP_Letter_IT_public | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Participant Card_IT_public | 1.0 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_Study_Drug_IT_public | 1.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Benerva | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_Eng_2023-506675-96-00 | 2.0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-12 | Italy | Acceptable 2024-10-28
|
2024-10-30 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-04-24 | Italy | Acceptable 2025-08-04
|
2025-08-04 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-06-01 | Italy | Acceptable 2025-08-04
|
2026-06-01 |