Low dose ColchicinE in pAtients with peripheral artery DiseasE to address residual vascular Risk: A randomized trial- LEADER PAD

Overview

Sponsor-declared trial summary

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

17 Jun 2025 → ongoing

Decision date (initial)

2025-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

1)Canadian Institute of Health Research 2) British Heart Foundation 3) National Institutes of Health

External identifiers

EU CT number

2024-512091-35-01

ClinicalTrials.gov

NCT04774159

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The overall objective of this research program is to examine the efficacy and safety of colchicine
0.5 mg/daily in reducing the incidence of cardiovascular death, myocardial infarction, stroke or
severe limb ischemia requiring an intervention including major vascular amputation in PAD
patients.

Conditions and MedDRA coding

Peripheral arterial disease

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age > 18 years
2. Symptomatic atherosclerotic LE PAD fulfilling at least one of the following: a. Intermittent claudication with ankle/arm blood pressure ratio* (ABI ≤ 0.90) or artery stenosis ≥ 50% plus one of i. >1 vascular bed affected by atherosclerosis ii. Diabetes iii. Heart failure iv. Chronic kidney disease (eGFR < 60 mL/min/1.73 m2); b. Rest pain (mostly in foot) OR necrosis of limb OR gangrene of limb (corresponding to either Fontaine stages 3 or 4 OR Rutherford Classification categories 4 to 6). All must have an ankle/arm blood pressure ratio* (ABI ≤ 0.90) OR artery stenosis ≥ 50%. * In cases of incompressible ankle arteries, the presence of toe pressure ≤ 60 mm Hg or toe-brachial index ≤ 0.70 is acceptable; c. Revascularization defined as limb bypass surgery or endovascular revascularization procedures (irrespective of the specific device used), including percutaneous transluminal angioplasty/stent of iliac or infra-inguinal arteries or extra-anatomical bypass surgery; or d. Leg or foot amputation for arterial vascular indications
3. Written informed consent from the patient

Exclusion criteria 13

1. Contraindication to colchicine (including hypersensitivity to the active substance or to any of the excipients)
2. Long term requirement for colchicine for another clinical indication
3. Active diarrhoea
4. eGFR < 30 mL/min/1.73 m2
5. Cirrhosis or severe chronic liver disease
6. Woman who is pregnant, or breast-feeding or of child-bearing potential not protected by reliable contraception or is planning conception during the study
7. Current or planned long term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (with the exception of azithromycin)
8. Patients who are deemed unlikely to return for follow-up
9. Patients with life expectancy < 1 year
10. Patients with blood dyscrasias
11. Patients with severe heart failure (NYHA class IV)
12. Patients with severe gastrointestinal insufficiency
13. Participation in a clinical trial in which an investigational drug was administered within 30 days of screening, or within the 5 half-lives of the study drug, whichever is longer

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of major adverse cardiovascular and limb events (MACE or MALE). This composite outcome consists of cardiovascular deaths, myocardial infarction, stroke, and severe limb ischemia that requires a vascular intervention (i.e., pharmacological reperfusion, endovascular or surgical revascularization) or a major vascular amputation (defined as ankle/transtibial amputation or higher).

Secondary endpoints 14

1. Extended MALE; This composite outcome includes major adverse limb events (MALE) as well as revascularization for new or worsening claudication of new stenosis or occlusion detected on screening after a previous intervention
2. Cardiovascular death
3. Myocardial infarction
4. Stroke
5. Hospitalization
6. Acute or chronic limb-threatening ischemia
7. All revascularization (coronary or cerebrovascular or lower limb or other peripheral revascularization)
8. Total vascular amputation
9. Overall mortality
10. Any thrombosis or thromboembolism (arterial and venous)
11. Fontaine Stage
12. Standard Assessment of Global Everyday Activities (SAGEA)
13. Vascular Quality of Life Questionnaire-6 (VascQOL-6)
14. EuroQol 5 Dimension 5 Level (EQ-5D-5L)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

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

Dr. Noel Chan, Central Study Investigator

Public contact point

Organisation

Hamilton Health Sciences Corporation

Contact name

LEADER-PAD Project Office

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications