Clinical trial NCT04916522: The COlchicine HypERtENsion Trial
Official title: COHERENT - The COlchicine HypERtENsion Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hypertension
Keywords: Inflammation
Vascular Stiffness
Pulse Wave Analysis
Blood Pressure
Echocardiography
Magnetic Resonance Imaging
Computed Tomography Angiography
Hypertrophy, Left Ventricular
Ventricular Function, Left
Endomyocardial Fibrosis
Atherosclerosis
Coronary Atherosclerosis
Colchicine
Cardiovascular Diseases
Heart Diseases
Randomized Controlled Trial
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2021-06-07
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Living address in the Capital Region of Denmark
2. Age \>18 years
3. Diagnosed with hypertension
4. Treatment with 1 or more antihypertensive medications
5. Must fulfill at least one of the following high-risk criteria:

   1. Diagnosed with type 2 diabetes mellitus OR
   2. Treatment with lipid-lowering medication for dyslipidemia OR
   3. Treatment with 2 or more antihypertensive medications
6. 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
7. Patients will have given written, informed consent and are able and willing to comply with the requirements of the study protocol

Exclusion Criteria:

1. Colchicine treatment for another cause, e.g. gout
2. Allergy/hypersensitivity to colchicine
3. Known or suspected secondary hypertension, e.g. renal artery stenosis
4. Uncontrolled hypertension (systolic BP \>180 mmHg or diastolic BP \>110 mmHg)
5. Known other cardiovascular disease (judged by the investigator), e.g. ischemic heart disease, heart failure, significant valvular disease, arrhythmia, stroke, or peripheral artery disease
6. 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
7. Cirrhosis, chronic active hepatitis or other severe hepatic disease
8. Hemodialysis
9. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2
10. Systemic treatment with moderate or strong cytochrome P450 3A4 (CYP3A4) inhibitors or P-glycoprotein inhibitors
11. Anemia, thrombocytopenia or leucopenia defined as any of the following measurements within the last 3 months:

    1. Hemoglobin \< 7 mmol/L
    2. Platelet count \< 110 x 10\^9/L
    3. White blood cell count \< 3.0 x 10\^9/L
12. Female patients who are pregnant, lactating, or considering becoming pregnant during the study or for 6 months after study completion
13. Significant drug or alcohol abuse during the last year
14. Current use of or plans to initiate chronic systemic steroid therapy during the study (topical or inhaled steroids are allowed)
15. Chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) or chronic diarrhea
16. Use of other investigational drugs within 30 days of the time of enrollment
17. 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.

Primary outcomes:
measure: Between-group difference in change in carotid-femoral pulse wave velocity at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Between-group difference in change in office-measured systolic blood pressure at 6 months
timeFrame: 6 months
measure: Between-group difference in change in office-measured diastolic blood pressure at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular mass assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular mass assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in high sensitivity C-reactive protein at 6 months
timeFrame: 6 months
measure: Between-group difference in change in high sensitivity Troponin I at 6 months
timeFrame: 6 months
Other outcomes:
measure: Between-group difference in change in office-measured pulse pressure at 6 months
timeFrame: 6 months
measure: Between-group difference in change in central blood pressure assessed by pulse wave analysis at 6 months
timeFrame: 6 months
measure: Between-group difference in change in augmentation index assessed by pulse wave analysis at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular septal wall thickness assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular posterior wall thickness assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular ejection fraction assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in E/A ratio assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in e' assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in E/e' assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in E/e'sr assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left atrial volume assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in global longitudinal strain assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in myocardial work assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in aortic distensibility assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in aortic strain assessed by echocardiography at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular septal wall thickness assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular posterior wall thickness assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left ventricular ejection fraction assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in left atrial volume assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in myocardial fibrosis assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in myocardial inflammation assessed by cardiac magnetic resonance imaging at 6 months
timeFrame: 6 months
measure: Between-group difference in change in tumor necrosis factor alpha at 6 months
timeFrame: 6 months
measure: Between-group difference in change in pro B-type natriuretic peptide at 6 months
timeFrame: 6 months
measure: Between-group difference in change in interleukin-1 beta at 6 months
timeFrame: 6 months
measure: Between-group difference in change in interleukin-6 at 6 months
timeFrame: 6 months
measure: Between-group difference in change in interleukin-10 at 6 months
timeFrame: 6 months
measure: Between-group difference in change in interleukin-17 at 6 months
timeFrame: 6 months
Locations:
city: Hellerup
country: Denmark
facility: Cardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology, Herlev and Gentofte Hospital
Study officials:
affiliation: Herlev and Gentofte Hospital
name: Niklas Dyrby Johansen, MD
role: PRINCIPAL_INVESTIGATOR
References: