Evaluation of Colchicine and Tiemonium Methylsulphate in Secondary Prevention of Cardiovascular Events in Moderate Chronic Renal Disease Patients
- Trial ID
- 2023-505868-11-00
- Protocol
- FIBHGM-ECNC002-2022
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the benefit of low-dose **colchicine** treatment (0.5 mg/day) in the secondary prevention of cardiovascular events in patients with moderate chronic kidney disease. The primary events of interest include cardiovascular death, acute coronary syndrome, angina requiring hospitalization, coronary revascularization, transient ischemic attack, non-cardioembolic ischemic stroke, and peripheral vasculopathy, which encompasses acute peripheral arterial embolism or ischemia, and the need for amputation or percutaneous surgical revascularization. This objective is clinically relevant as it aims to reduce the incidence of severe cardiovascular complications in a population with an elevated risk due to underlying renal impairment.
The secondary objectives of the study are as follows:
- To evaluate the efficacy in the prevention of each vascular event separately.
- To assess the effect on renal disease progression.
- To describe the effect on molecular markers of inflammation, fibrosis, and renal progression.
- To determine the safety of the treatment.
Participants
The clinical trial involves participants diagnosed with **chronic renal disease**, specifically targeting individuals with moderate chronic kidney disease. The study population includes both male and female subjects, aged between 18 and 99 years, who have a history of previous cardiovascular events. These events may include acute coronary syndrome, angina requiring hospitalization, transient ischemic attack, non-cardioembolic ischemic stroke, coronary revascularization, or peripheral vasculopathy. Participants are required to have a glomerular filtration rate estimated by the CKD-EPI formula between 30 and 59 mL/min/1.73m². The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include legal capacity and voluntary willingness to sign informed consent. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **colchicine** in the secondary prevention of vascular events and renal progression in patients with moderate **chronic renal disease**. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the treatment or placebo, thus minimizing bias. The trial is expected to last approximately 36 months, with recruitment starting on April 1, 2024, and the estimated end date being July 1, 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age between 18 and 99 years, a history of cardiovascular events, and moderate chronic kidney disease as defined by a specific glomerular filtration rate. Following successful screening, participants will be randomized to receive either colchicine or a placebo. The study will include regular follow-up visits to monitor the incidence of primary and secondary endpoints, such as cardiovascular events and changes in renal function. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted.
The expected length of participant involvement is the full duration of the trial, approximately 36 months, unless early termination is warranted. Conditions that may lead to early termination include adverse events, withdrawal of consent, or any situation where continued participation is deemed unsafe or not in the participant's best interest. The trial aims to provide valuable insights into the potential benefits of colchicine in managing chronic renal disease and associated cardiovascular risks.
Treatment
The clinical trial involves the administration of **colchicine** as the experimental medication. Colchicine is provided in a pharmaceutical form identified as PHF00082MIG. The active substances in this formulation include **colchicine** and **tiemonium methylsulphate**. The medication is administered orally at a dosage of 0.5 mg per day. The maximum treatment period for this trial is 36 months. The trial aims to evaluate the efficacy of low-dose colchicine in the secondary prevention of cardiovascular events and renal progression in patients with moderate chronic kidney disease. Participant compliance with the dosing schedule will be monitored throughout the study.
In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is designed to match the experimental medication in appearance and administration route to ensure blinding. The placebo is administered orally with the same frequency as the experimental treatment, maintaining the integrity of the study design. The use of a placebo allows for the assessment of the true efficacy of colchicine by providing a baseline for comparison.
Efficacy
The efficacy of the clinical trial titled "EFFICACY OF COLCHICINE IN SECONDARY PREVENTION OF VASCULAR EVENTS AND RENAL PROGRESSION IN PATIENTS WITH MODERATE CHRONIC RENAL DISEASE (COLCHIREN STUDY)" will be assessed through a series of primary and secondary endpoints. The primary endpoints focus on the incidence of cardiovascular events, including death from cardiovascular causes, acute coronary syndrome, angina requiring hospitalization, coronary revascularization, transient ischemic attack, non-cardioembolic ischemic stroke, and peripheral vascular disease, defined as acute peripheral arterial embolism or ischemia, or the need for amputation or percutaneous surgical revascularization.
Secondary endpoints will evaluate the incidence of individual cardiovascular events, such as death from cardiovascular causes, acute coronary syndrome, hospitalization for cardiac angina, coronary revascularization, transient ischemic attack, and peripheral vasculopathy. Additionally, the trial will assess renal events, including a 40% decrease in glomerular filtration rate estimated by CKD-EPI, doubling of serum creatinine, a persistent drop in glomerular filtration rate below 15 mL/min/1.73m², and the need for sustained renal replacement therapy. The effect on plasma levels of markers of inflammation, fibrosis, and renal progression, as well as the incidence of adverse events, will also be measured.
The trial aims to determine the benefit of low-dose **colchicine** treatment (0.5 mg/day) in patients with moderate chronic kidney disease. The study will utilize validated clinical assessments and laboratory tests to collect and analyze data at specified timepoints throughout the trial duration, which is estimated to conclude by July 2027.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 01 Apr 2024 | 744 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
clochicine | Placebo | N/A | — | — | — | N/A |
COLCHICINE | Test | PHF00082MIG | ORAL | 0.5 | 36 | SCP129899 |