The COlchicine HypERtENsion Trial

Study Overview
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Brief Summary
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The purpose of this study to investigate the effects of colchicine on measures of vascular and cardiac function in patients with hypertension.

Detailed Description
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The study is an investigator-initiated, prospective, double-blind, placebo-controlled, randomized clinical trial investigating the effects of colchicine in patients with hypertension. The study population will consist of approximately 150 patients aged 18 years and above with a diagnosis of hypertension and in active treatment with at least 1 antihypertensive drug. Patients will be randomized to either low-dose colchicine treatment (0,5 mg once daily) or placebo. Treatment will continue for 6 months. Patients will be assessed by measurement of pulse wave velocity (PWV), office blood pressure, echocardiography, cardiac MRI, and blood samples at baseline and after 6 months.

Official Title
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COHERENT - The COlchicine HypERtENsion Trial

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Colchicine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living address in the Capital Region of Denmark Age >18 years Diagnosed with hypertension Treatment with 1 or more antihypertensive medications Must fulfill at least one of the following high-risk criteria: Diagnosed with type 2 diabetes mellitus OR Treatment with lipid-lowering medication for dyslipidemia OR Treatment with 2 or more antihypertensive medications Female patients should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing one of the following methods of contraception throughout the study and for 30 days after study completion: Hormonal contraception (oral contraceptives, contraceptive implant, injectable birth control, contraceptive patch, or vaginal ring) or intrauterine device Patients will have given written, informed consent and are able and willing to comply with the requirements of the study protocol Exclusion Criteria: Colchicine treatment for another cause, e.g. gout Allergy/hypersensitivity to colchicine Known or suspected secondary hypertension, e.g. renal artery stenosis Uncontrolled hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg) Known other cardiovascular disease (judged by the investigator), e.g. ischemic heart disease, heart failure, significant valvular disease, arrhythmia, stroke, or peripheral artery disease History of malignancy of any organ system excluding a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, localized prostate cancer and/or localized carcinoma in situ of the cervix Cirrhosis, chronic active hepatitis or other severe hepatic disease Hemodialysis Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 Systemic treatment with moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors or P-glycoprotein inhibitors Anemia, thrombocytopenia or leucopenia defined as any of the following measurements within the last 3 months: Hemoglobin < 7 mmol/L Platelet count < 110 x 10^9/L White blood cell count < 3.0 x 10^9/L Female patients who are pregnant, lactating, or considering becoming pregnant during the study or for 6 months after study completion Significant drug or alcohol abuse during the last year Current use of or plans to initiate chronic systemic steroid therapy during the study (topical or inhaled steroids are allowed) Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) or chronic diarrhea Use of other investigational drugs within 30 days of the time of enrollment Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Colchicine<br>Colchicine 0.5 mg once daily | Drug: Colchicine<br>* 0.5 mg once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Drug: Placebo<br>* Once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group difference in change in carotid-femoral pulse wave velocity at 6 months |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group difference in change in office-measured systolic blood pressure at 6 months |  | 6 months | 
| Between-group difference in change in office-measured diastolic blood pressure at 6 months |  | 6 months | 
| Between-group difference in change in left ventricular mass assessed by echocardiography at 6 months |  | 6 months | 
| Between-group difference in change in left ventricular mass assessed by cardiac magnetic resonance imaging at 6 months |  | 6 months | 
| Between-group difference in change in high sensitivity C-reactive protein at 6 months |  | 6 months | 
| Between-group difference in change in high sensitivity Troponin I at 6 months |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Computed Tomography Angiography, Hypertrophy, Left Ventricular, Ventricular Function, Left, Colchicine, Cardiovascular Diseases, Heart Diseases, Randomized Controlled Trial, Endomyocardial Fibrosis, Atherosclerosis, Coronary Atherosclerosis, Inflammation, Vascular Stiffness, Pulse Wave Analysis, Blood Pressure, Echocardiography, Magnetic Resonance Imaging