Low-dose colchicine in patients with circulatory disorders in the legs to reduce the risk of cardiovascular events such as stroke, heart attack, or amputation
Descrizione riassuntiva dello studio
In this study, we investigate how well the study drug colchicine works in patients with peripheral arterial disease (PAD). We want to find out if taking colchicine can prevent further vascular complications and whether it is well tolerated. To this end, eligible participants will be randomly assigned to a group. Half of the participants will receive the study drug at a dosage of 0.5 mg once daily, and the other half will receive a placebo, which is a tablet without an active ingredient. The study is a double-blind study. "Double-blind" means that no one involved in the conduct of the study knows which group the participants have been assigned to. This is to prevent anyone from influencing the study. Eligible participants will undergo a 2-week test phase during which they will take 0.5 mg of colchicine daily. Participants who tolerate colchicine will then be included in the study. After that, participants will be interviewed every six months about their health status, for a minimum of one year and a maximum of five years. Once 6150 people are enrolled, the study will end.
(BASEC)
Intervento studiato
In our study, participants will be randomly assigned to two groups. This is important to obtain reliable results from the study. This is called randomization. Each group receives a different treatment:
• Group 1 (experimental group) receives the study drug at a dosage of 0.5 mg
• Group 2 (control group) receives a placebo, which is a tablet without an active ingredient
Participation in the study is voluntary and lasts at least one year and a maximum of five years.
Eligible participants will undergo a 2-week test phase during which they will take 0.5 mg of colchicine daily. Participants who tolerate colchicine will then be included in the study. After that, participants will be interviewed every six months about their health status. Additionally, study participants will be contacted by phone twice in the first year, after three and nine months. During all study visits, questions will be asked about health status and the tolerability of the study drug.
(BASEC)
Malattie studiate
Peripheral arterial disease (PAD) is a common vascular disease, particularly in older adults. PAD is caused by the buildup of fatty deposits (atherosclerotic plaques) in inflamed arteries, which block blood flow in the legs. Reduced blood flow in the legs can lead to leg pain and limit walking ability. Other arteries, such as those supplying blood to the heart or brain, may also be affected. A blood clot that forms in inflamed arteries can completely block blood flow and lead to complications such as amputation, heart attack, and stroke. Standard treatments for PAD include surgeries (to open the arteries), anticoagulant medications, blood pressure medications, and cholesterol-lowering medications. In the LEADER-PAD study, we will investigate whether the anti-inflammatory drug colchicine reduces vascular complications in patients with PAD. There is already research on humans regarding PAD. Previous studies in humans have shown that despite treatment, about 5-30% of patients experience serious complications. Most of these treatments do not primarily target the inflammations that block the arteries. We already know that in patients with heart attack or angina pectoris (chest pain), colchicine reduces the rate of vascular complications by about 25%, but it has not yet been studied in people with PAD. People with PAD might benefit even more, as they have more deposits in their arteries throughout the body. Therefore, in this study, we investigate whether the anti-inflammatory study drug colchicine (not approved for the treatment of PAD) is effective in PAD. We want to examine whether colchicine can also reduce vascular complications (cardiovascular death, heart attack, stroke, or sudden lack of blood flow to your leg requiring treatment) in patients with PAD. The investigational substance colchicine contains the active ingredient colchicinum, an alkaloid of the autumn crocus. The study drug colchicine is currently approved in Switzerland for the treatment of gout and a rarer inflammatory disease known as familial Mediterranean fever (FMF). Only when the efficacy of the investigational substance colchicine for the treatment of PAD has been scientifically investigated and proven can it be approved in Switzerland and used for the treatment of PAD.
(BASEC)
1. Age > 18 years 2. Symptomatic atherosclerotic peripheral arterial disease (PAD) of the lower extremities, meeting at least one of the following criteria: a. Intermittent claudication with an ankle-brachial index* (ABI ≤ 0.90) or an arterial stenosis ≥ 50% plus one of the following: i. > 1 vascular territory affected by atherosclerosis ii. Diabetes iii. Heart failure iv. Chronic kidney disease (eGFR < 60 mL/min/1.73 m²) b. Rest pain (usually in the foot) OR necrosis of the limb OR gangrene of the limb (corresponding to Fontaine stage 3 or 4 OR Rutherford categories 4 to 6). All must have an ankle-brachial index* (ABI ≤ 0.90) OR an arterial stenosis ≥ 50%. *For non-compressible ankle arteries, the presence of a toe pressure ≥ 60 mm Hg or a toe-brachial index ≤ 0.70 is acceptable. c. Revascularization, defined as bypass surgery of the limbs or endovascular revascularization procedures (regardless of the specific device used), including percutaneous transluminal angioplasty/stenting of the iliac or infrainguinal arteries or extra-anatomical bypass surgeries. d. Amputation of the leg or foot for arterial vascular indications. 3. Written or oral consent of the patient. (BASEC)
Criteri di esclusione
1. Contraindication to colchicine 2. Long-term need for colchicine for another clinical reason 3. Acute diarrhea 4. eGFR < 30 mL/min/1.73 m² 5. Liver cirrhosis or severe chronic liver disease 6. Women who are pregnant, breastfeeding, or of childbearing age who are not protected by reliable contraceptive methods or who plan a pregnancy during the study 7. Current or planned long-term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (except azithromycin) 8. Patients who are unlikely to return for follow-up visits 9. Patients with a life expectancy < 1 year (BASEC)
Luogo dello studio
Basilea, Bellinzona, Friburgo, Ginevra, Zurigo
(BASEC)
Sponsor
Universitätsspital Zürich
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Rebecca Spescha
+41 43 253 03 71
rebecca.spescha@clutterusz.chUniversitätsspital Zürich, Klinik für Angiologie, Rämistrasse 100, 8091 Zürich
(BASEC)
Informazioni generali
Population Health Research Institute, Hamilton, Ontario, Canada
905-521-2100
Noel.Chan@TAARI.CA(ICTRP)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione etica Zurigo
(BASEC)
Data di approvazione del comitato etico
15.10.2024
(BASEC)
ID di studio ICTRP
NCT04774159 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
Low dose ColchicinE in pAtients with peripheral artery DiseasE to address residual vascular Risk: A randomized trial (BASEC)
Titolo accademico
Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk: A Randomized Trial (ICTRP)
Titolo pubblico
Low Dose ColchicinE in pAtients With Peripheral Artery DiseasE to Address Residual Vascular Risk (ICTRP)
Malattie studiate
Peripheral Arterial DiseaseAtherosclerosis of ExtremitiesInflammation (ICTRP)
Intervento studiato
Drug: Colchicine 0.5 MG Oral TabletDrug: Colchicine-Placebo (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Criteri di inclusione/esclusione
Inclusion criteria:
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
d. Leg or foot amputation for arterial vascular indications
3. Written or verbal informed consent from the patient
Exclusion Criteria:
1. Contraindication to colchicine
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 (ICTRP)
non disponibile
Endpoint primari e secondari
Major adverse cardiovascular and limb events (MACE or MALE) (ICTRP)
Extended MALE;Cardiovascular death;Myocardial infarction;Stroke;Hospitalization;Acute or chronic limb-threatening ischemia;All revascularization (coronary or cerebrovascular or lower limb or other peripheral revascularization);Total vascular amputation;Overall mortality;Any thrombosis or thromboembolism (arterial and venous);Fontaine Stage;Standard Assessment of Global Everyday Activities (SAGEA);Vascular Quality of Life Questionnaire-6 (VascQOL-6);EuroQol 5 Dimension 5 Level (EQ-5D-5L) (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
non disponibile
Contatti aggiuntivi
Noel C Chan, MDNoel C Chan, MD, Noel.Chan@TAARI.CA, 905-521-2100, Population Health Research Institute, Hamilton, Ontario, Canada (ICTRP)
ID secondari
LEADER-PAD (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT04774159 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile