The COLchicine HEART Failure PRESERVED Trial (COLHEART-PRESERVED)

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of colchicine on heart failure related health status, quality of life, and vascular and cardiac function in patients with heart failure with preserved ejection fraction (HFpEF).

Detailed Description
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The study is an investigator-initiated, prospective, randomized, double-blind, placebo-controlled study of the effects of colchicine in patients with HFpEF. The study population will consist of approx. 152 patients aged 40 years and above, who meet the criteria of HFpEF. Patients will be randomized to either low-dose colchicine treatment (0.5 mg once daily) or placebo and treatment will continue for 6 months. Patients will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and have echocardiography performed at baseline and after 6 months. Furthermore, the investigators will obtain office blood pressure, ECG, Myovista ECG, 6-minute walk test, pulse wave velocity (PWV), and blood samples at baseline and after 6 months.

Official Title
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The COLchicine HEART Failure PRESERVED Trial (COLHEART-PRESERVED)

Conditions
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Heart Failure With Preserved Ejection Fraction

Intervention / Treatment
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* Drug: Colchicine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LVEF ≥ 45% judged by echocardiography during the screening epoch or within 6 months prior to screening visit Symptom(s) of heart failure for at least 30 days prior to screening visit and current symptoms of heart failure (NYHA functional class II-IV) at screening visit Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures (left atrial enlargement and/or left ventricular hypertrophy) judged by echocardiography at screening epoch or within 12 months prior to screening visit Raised pro-BNP ≥ 125 pg/ml (sinus rhythm) or ≥ 300 pg/ml (atrial fibrillation (AF)). Body Mass Index (BMI) < 40 kg/m2 at screening visit Female patients should either not be of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or 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 Uncontrolled hypertension (systolic BP >180 mmHg or diastolic BP >110 mmHg) 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) < 35 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 109/L White blood cell count < 3.0 x 109/L Acute decompensated heart failure (hospitalization for heart failure within 7 days prior to screening visit) Acute coronary syndrome (including MI), cardiac surgery, other major cardiovascular surgery, ablation of atrial flutter/fibrillation, valve repair/replacement, implanted cardioverter defibrillator or urgent PCI within 3 months prior to screening visit or an elective PCI within 30 days prior to screening visit Planned coronary revascularization (percutaneous intervention or surgical), major cardiac surgery (coronary artery bypass grafting, valve repair/replacement, ventricular assist device, cardiac transplantation, or any other surgery requiring thoracotomy), CRT or ablation of atrial flutter/fibrillation during the trial Any clinical event within 6 months prior to screening visit that could have reduced LVEF (e.g., MI, CABG), unless echocardiographic measurement was performed after the event confirming LVEF ≥ 45% Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within 3 months prior to screening visit Previous cardiac transplantation, complex congenital heart disease or cardiac resynchronization therapy Heart failure due to any of the following: known infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy, obstructive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or uncorrected severe/hemodynamically significant valvular heart disease Life threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and AF or atrial flutter with a resting ventricular rate > 110 beats per minute Evidence of right-sided HF in the absence of left sided structural heart disease Probable alternative diagnosis that in the opinion of the investigator could account for the patient's HF symptoms (i.e., anemia, hypothyroidism, severe obesity) World Health Organization Group 1 pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease, including COPD (i.e., requiring home oxygen, chronic nebulizer therapy or chronic oral steroid therapy, or hospitalization for exacerbation of COPD requiring ventilatory assist within 12 months prior to enrollment) 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 Life expectancy < 2 years at the screening visit

Ages Eligible for Study
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Minimum Age: 40 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 Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) at 6 months | The Kansas City Cardiomyopathy Questionnaire scores are scaled from 0-100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; 75 to 100; good to excellent. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-group difference in change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at 6 months | The Kansas City Cardiomyopathy Questionnaire scores are scaled from 0-100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; 75 to 100; good to excellent. | 6 months | 
| Between-group difference in the proportion of patients with a ≥ 5-point increase in KCCQ-CS and KCCQ-OS at 6 months | The Kansas City Cardiomyopathy Questionnaire scores are scaled from 0-100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; 75 to 100; good to excellent. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular Diseases, Colchicine, Quality of Life, Randomized Controlled Trial, Heart Diseases, Inflammation, Echocardiography, Hypertrophy, Left Ventricular, Ventricular Function, Left, Diastolic Dysfunction, Left Ventricular, Atrial Enlargement, Left, Kansas City Cardiomyopathy Questionnaire