Colchicine in Secondary Prevention of Vascular Events and Renal Progression in Patients with Moderate Chronic Renal Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

17 Jan 2025 → ongoing

Decision date (initial)

2024-04-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Instituto de Salud Carlos III

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis

To assess the benefit of low-dose colchicine treatment (0. 5 mg/day) in the secondary prevention of cardiovascular events (incidence of the primary event consisting of: cardiovascular death; acute coronary syndrome; angina requiring hospitalisation; coronary revascularisation; transient ischaemic attack or non-cardioembolic ischaemic stroke; or peripheral vasculopathy, defined as acute peripheral arterial embolism or ischaemia, or need for amputation or percutaneous surgical revascularisation) in patients with moderate chronic kidney disease

Secondary objectives 4

1. - To evaluate the efficacy in the prevention of each vascular event separately.
2. - To assess the effect on renal disease progression.
3. - To describe the effect on molecular markers of inflammation, fibrosis and renal progression.
4. To determine the safety of the treatment.

Conditions and MedDRA coding

CHRONIC RENAL DISEASE

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Age between 18 and 99 years. - Moderate chronic kidney disease, defined as a glomerular filtration rate estimated by the CKD-EPI formula between 30 and 59 mL/min/1.73m2. - History of having suffered a previous cardiovascular event: o Acute coronary syndrome. o Admission for angina pectoris. o Transient ischemic attack or non-cardioembolic ischemic stroke. o Coronary revascularization. o Confirmed diagnosis of peripheral vascular disease (PVD) based on clinical criteria and/or imaging studies, including:  Decreased or absent pulses in the femoral, popliteal, tibial or pedial arteries with clinical signs of intermittent claudication or.  Abnormal results on blood flow studies: ankle-brachial index (ABI) less than 0.9 or.  Angiographic evidence of stenosis, occlusions or aneurysms in peripheral arteries. . o Finding of coronary artery disease on imaging test. - Legal capacity and voluntary willingness to sign informed consent.

Exclusion criteria 3

1. - History of allergy or intolerance to colchicine or any of its excipients (calcium hydrogen phosphate dihydrate, microcrystalline cellulose, anhydrous colloidal silica, magnesium stearate). - Current treatment with colchicine, or during the month prior to inclusion. - Hospital admission of any cause in the 3 months prior to inclusion in the study. - Active malignant neoplasm (except non-melanoma skin cancer or carcinoma in situ). Patients with a history of malignant neoplasia who have remained free of disease during the previous 3 years can be included. - Uncontrolled or symptomatic chronic inflammatory disease (rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, etc.). - Active infection by hepatitis B virus, hepatitis C virus or human immunodeficiency virus. - Liver cirrhosis of any cause Child-Pugh grade B or C. - Immunosuppressive treatment in the 12 weeks prior to inclusion in the study. - Chronic treatment with non-steroidal anti-inflammatory drugs. - Poorly controlled arterial hypertension (>160/90 mmHg) at the inclusion visit.
2. - Pregnancy and lactation in the inclusion. The use of contraceptive methods is required for women with gestational capacity. Women with gestational capacity are not considered those with: o History of hysterectomy, double salpingectomy, double oophorectomy, or bilateral tubal ligation. o Documented infertility. o Postmenopausal women, defined as amenorrhea for more than 12 months with no other medical cause. In case of doubt, confirmation with elevated follicle stimulating hormone (FSH) levels is recommended. In women with gestational capacity, the use of a contraceptive method of proven effectiveness is required up to 8 weeks after the end of the study. Acceptable methods are as follows: o intrauterine device (IUD) implantation at least 6 weeks prior to study inclusion. o Progestogen-only hormonal contraception associated with ovulation inhibition: oral, injectable, implantable at least 6 weeks prior to study enrollment. o Intrauterine progestin-releasing system at least 6 weeks prior to study enrollment. Combined hormonal contraception (containing estrogens and progestogens) associated with ovulation inhibition : oral, intravaginal , transdermal at least since 6 weeks prior to study inclusion. Other contraceptive methods (sexual abstinence, barrier methods, spermicides, etc.) are not considered acceptable for the study.
3. - Gastric ulcer. - Thrombocytopenia defined as <50000 cells/mcL during the month prior to inclusion. - Neutropenia defined as <1500 cells/mcL during the month prior to inclusion. - Anemia defined as hemoglobin <10.5 g/dL during the month prior to inclusion. - History of aplastic anemia diagnosed by bone marrow biopsy. - Treatment with CYP3A4 and/or P-glycoprotein inhibitors (antivirals, azole antifungals, aminoglycosides, cisclosporin) in the month prior to inclusion in the trial. Treatment with CYP3A4 and/or P-glycoprotein inhibitors (antivirals, azole antifungals, aminoglycosides, cisclosporin) in the month prior to inclusion in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. incidence of the primary event consisting of: death from cardiovascular causes; acute coronary syndrome; angina requiring hospitalisation; coronary revascularisation; transient ischaemic attack or non-cardioembolic ischaemic stroke; or peripheral vascular disease, defined as acute peripheral arterial embolism or ischaemia, or the need for amputation or percutaneous surgical revascularisation
2. Incidence of primary event consisting of death from cardiovascular causes; acute coronary syndrome; angina requiring hospitalization; coronary revascularization; transient ischemic attack or noncardioembolic ischemic stroke; or peripheral vasculopathy, defined as embolism or acute peripheral arterial ischemia, or need for amputation or surgical or percutaneous revascularization.

Secondary endpoints 2

1. - Incidence of death from cardiovascular causes. - Incidence of acute coronary syndrome. - Incidence of hospitalization for cardiac angina. - Incidence of coronary revascularization. - Incidence of transient ischemic attack or noncardioembolic ischemic stroke. - Incidence of peripheral vasculopathy, defined as embolism or acute peripheral arterial ischemia, or need for amputation or percutaneous surgical revascularization.
2. - Individual and combined incidence of renal events: o 40% decrease in glomerular filtration rate estimated by CKD-EPI with respect to baseline. o Doubling of serum creatinine over its baseline level. o Persistent drop in glomerular filtration rate estimated by CKD-EPI below 15 mL/min/1.73m2. o Need for renal replacement therapy on a sustained basis. - Effect on plasma levels of markers of inflammation, fibrosis and renal progression. - Incidence of adverse events.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Sponsor organisation

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Address

Calle Del Dr. Esquerdo 46

City

Madrid

Postcode

28007

Country

Spain

Scientific contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Contact name

María del Carmen de la Cruz

Public contact point

Organisation

Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon

Contact name

María del Carmen de la Cruz

Locations

1 EU/EEA country · 27 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 11 files

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

Application history

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