Evaluation of Colchicine on Health Status in Patients with Heart Failure with Preserved Ejection Fraction: A Randomized, Placebo-Controlled Trial
- Trial ID
- 2023-506207-26-00
- Sponsor
- Gentofte Hospital
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the effect of **colchicine**, compared with placebo, on heart failure-related health status using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) in patients with **heart failure with preserved ejection fraction (HFpEF)**. This is clinically relevant as it aims to determine whether colchicine can improve the quality of life and functional status in this patient population, which is crucial for managing a condition with limited treatment options.
Secondary objectives include:
- Investigating the effect of colchicine on heart failure-related health status using the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) compared to placebo.
- Assessing the proportion of patients achieving a ≥ 5-point increase in KCCQ-CS and KCCQ-OS when treated with colchicine versus placebo.
Participants
The clinical trial focuses on individuals diagnosed with **heart failure with preserved ejection fraction (HFpEF)**. The study population includes both male and female participants aged 40 years and older. Participants are required to have a left ventricular ejection fraction (LVEF) of 45% or higher, as determined by echocardiography, and must exhibit symptoms of heart failure for at least 30 days prior to the screening visit. The trial does not involve a vulnerable population. Participants must have objective evidence of cardiac structural or functional abnormalities, such as left atrial enlargement or left ventricular hypertrophy, and elevated pro-BNP levels. The study excludes individuals with a body mass index (BMI) of 40 kg/m² or higher. Female participants must either be postmenopausal, surgically sterile, or practicing effective contraception. The sponsor has not provided the total number of participants involved in the trial.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **colchicine** in patients with **heart failure with preserved ejection fraction (HFpEF)**. This study is a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is expected to last until January 2026, with recruitment starting in November 2023. Participants will be involved for a maximum treatment period of six months, during which they will receive either colchicine or a placebo orally. The primary objective is to assess the impact of colchicine on heart failure-related health status using the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS).
Study visits are structured to include an initial screening visit, where eligibility is confirmed based on criteria such as age, left ventricular ejection fraction, and symptoms of heart failure. Participants must be at least 40 years old, have a left ventricular ejection fraction of 45% or higher, and exhibit symptoms consistent with heart failure. Follow-up visits will occur periodically to monitor health status and adherence to the study protocol. The end-of-study visit will conclude the participant's involvement, with final assessments conducted to evaluate the primary and secondary endpoints, including changes in the KCCQ-CS and Overall Summary Score (KCCQ-OS).
Participants may be withdrawn from the study if they fail to comply with the study protocol, experience adverse effects that necessitate discontinuation, or choose to withdraw consent. The trial's design and procedures are meticulously planned to ensure the collection of reliable data while prioritizing participant safety and adherence to ethical standards.
Treatment
The clinical trial involves the administration of **Colchicine**, marketed under the name Colrefuz 500 mikrogram tabletter. This experimental medication is provided in the form of a tablet, with each tablet containing 500 micrograms of the active substance. The route of administration is oral. Participants will receive a maximum daily dose of 0.5 mg, with a total maximum dose of 90 mg over the course of the study. The treatment period is set for a maximum of 6 months. The pharmaceutical product is manufactured by TEVA B.V and is classified under the ATC code M04AC01. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.
The study also includes a **placebo** group for comparison purposes. The placebo is designed to be identical in appearance to the Colrefuz tablets and contains the following inactive ingredients: lactose monohydrate, potato starch, spiritus gelatinae 5%, magnesium stearate, and talcum. The placebo is also administered orally, following the same dosing schedule as the experimental medication. The use of a placebo allows for the assessment of the true efficacy of colchicine by providing a baseline for comparison. Participant compliance with the placebo regimen will be similarly monitored to maintain the integrity of the study results.
Efficacy
Efficacy in the clinical trial titled "The Colchicine heart failure preserved trial" will be assessed by evaluating the effect of **colchicine** compared to placebo on heart failure-related health status. The primary endpoint for efficacy assessment is the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS). This validated tool will be used to measure the health status of patients with heart failure, providing a comprehensive assessment of symptoms, physical limitations, and quality of life.
Secondary endpoints include the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) and the proportion of patients achieving a ≥ 5-point increase in both KCCQ-CS and KCCQ-OS compared to placebo. These endpoints will help determine the broader impact of colchicine on patient health status and symptom improvement. The efficacy parameters will be collected and analyzed at specified timepoints throughout the trial, ensuring a robust evaluation of the treatment's impact on heart failure with preserved ejection fraction.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 40 years
- LVEF ≥ 45% 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 within the past 5 years 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 10˄9/L, White blood cell count < 3.0 x 10˄9/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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Recruiting | 01 Nov 2023 | 152 |
Sites & Investigators
Research 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 |
|---|---|---|---|---|---|---|
Placebo will be identical in appearance and contain the following ingredients: lactosemonohydrate, potato starch, spiritus gelatinae 5%, magnesium stearate, talcum. | Placebo | N/A | ORAL | — | 6 | N/A |
Colrefuz 500 mikrogram tabletter | Test | TABLETTER | ORAL | 0.5 | 6 | PRD2811442 |