Efficacy of Colchicine in Secondary Prevention of Vascular Events and Renal Progression in Patients With Moderate Chronic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 744
- 试验地点
- 1
- 主要终点
- Cardiovascular events
研究概览
简要总结
The ColchiRen study is a phase 3, controlled, prospective, randomized, double-blind, and multicenter clinical trial. Its main objective is to demonstrate the benefit of low-dose colchicine treatment in secondary prevention of cardiovascular events in patients with moderate CKD. As a secondary objective, it aims to explore the potential beneficial anti-inflammatory effect on the progression of CKD.
详细描述
A total of 744 patients will be included (50% in each branch), and the follow-up time of the study will be three years.
EXPLORATORY PARAMETERS
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Analytical parameters in blood:
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Hemogram: hemoglobin, erythrocyte sedimentation rate.
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Biochemistry: creatinine, glomerular filtration rate estimated by CKD-EPI, glucose, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, C-reactive protein, fibrinogen, glycosylated hemoglobin.
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Analytical parameter in urine: albumin/creatinine ratio in first morning urine.
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Parameters in samples centralized in the Renal Pathophysiology Laboratory: array including more than 40 molecules that promote and inhibit inflammation and fibrosis; measurement of ACE and ACE2.
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Cardiovascular events defined as one of the following:
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Cardiovascular death.
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Acute coronary syndrome.
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Angina requiring hospitalization.
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Coronary revascularization.
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Transient ischemic attack or noncardioembolic ischemic stroke.
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Peripheral vascular disease, defined as acute peripheral arterial embolism or ischemia, or need for amputation or percutaneous surgical revascularization.
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Renal event, defined as one of the following:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 99 years. Moderate chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) by the CKD-EPI formula between 30 and 59 mL/min/1.73 m².
- •History of a previous cardiovascular event:
- •Acute coronary syndrome. Admission for angina pectoris. Transient ischemic attack or non-cardioembolic ischemic stroke. Coronary revascularization. Peripheral vasculopathy, defined as: embolism or acute peripheral arterial ischemia, or the need for amputation or surgical revascularization.
- •Finding of coronary artery disease on imaging test.
排除标准
- •History of allergy or intolerance to colchicine or any of its excipients (dihydrate calcium hydrogen phosphate, microcrystalline cellulose, anhydrous colloidal silica, magnesium stearate).
- •Current treatment with colchicine, or within the month prior to inclusion.
- •Hospital admission for any cause within the 3 months prior to study inclusion.
- •Active malignant neoplasm (except non-melanoma skin cancer or carcinoma in situ). Patients with a history of malignant neoplasm who have remained disease-free for the past 3 years may be included.
- •Uncontrolled or symptomatic chronic inflammatory disease (rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, etc.).
- •Active infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus.
- •Liver cirrhosis of any cause, grade B or C according to Child-Pugh.
- •Immunosuppressive treatment within the 12 weeks prior to study inclusion.
- •Chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs).
- •Poorly controlled hypertension (>160/90 mmHg) at the time of inclusion.
- •Pregnancy and breastfeeding at the time of inclusion. Contraceptive methods are required for women of reproductive age. Women with no capacity for pregnancy are considered to be those with:
- •History of hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral tubal ligation.
- •Documented infertility. Postmenopausal women, defined as amenorrhea for more than 12 months without other medical cause. In case of doubt, confirmation with elevated follicle-stimulating hormone (FSH) levels is recommended.
- •Women of reproductive capacity must use a method of contraception with proven effectiveness until 8 weeks after the end of the study. Acceptable methods include:
- •Intrauterine device (IUD) placement at least 6 weeks before study inclusion. Hormonal contraception with progestogens only, associated with ovulation inhibition: oral, injectable, or implantable, at least 6 weeks before study inclusion.
- •Progestin-releasing intrauterine system (IUS) at least 6 weeks before study inclusion.
- •Combined hormonal contraception (containing estrogen and progestogens) associated with ovulation inhibition: oral, intravaginal, transdermal, at least 6 weeks before study inclusion.
- •Other contraceptive methods (sexual abstinence, barrier methods, spermicides, etc.) are not considered acceptable for participation in this study
- •Gastric ulcer
- •thrombocytopenia <50,000 cells/μL 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 through bone marrow biopsy.
- •Treatment with CYP3A4 inhibitors and/or P-glycoprotein inhibitors (antivirals, azole antifungals, aminoglycosides, cyclosporine) in the month prior to their inclusion in the study.
研究组 & 干预措施
Colchicine treatment
after randomization, a 0.5 mg tablet of colchicine per day will be administered.
干预措施: colchicine treatment in chronic kidney disease patients (Drug)
placebo treatment
after randomization 0,25 mg of placebo per day will be administered
干预措施: placebo treatment (Drug)
结局指标
主要结局
Cardiovascular events
时间窗: from enrollment to the end of treamtent at three years
Incidence of the primary event consisting of death due to cardiovascular causes; acute coronary syndrome; angina requiring hospitalization; coronary revascularization; transient ischemic attack or non-cardioembolic ischemic stroke; or peripheral vasculopathy, defined as embolism or acute peripheral arterial ischemia, or the need for amputation or surgical or percutaneous revascularization."
次要结局
- cardiovascular death(from enrollment to the end of treamtent at three years)
- Angina pectoris(from enrollment to the end of treamtent at three years)
- stroke(from enrollment to the end of treamtent at three years)
- Acute coronary syndrome(from enrollment to the end of treamtent at three years)
- Peripheral vasculopathy(from enrollment to the end of treamtent at three years)
- renal disease progression(from enrollment to the end of treamtent at three years)
- effect of colchcine treatment on inflammation and fibrosis parameters(from enrollment to the end of treatment at three years)
- Security(from enrollment to the end of treatment at three years)