Colchicine in HFpEF (COLpEF)

This is an interventional treatment trial for Heart Failure Read More

Inclusion Criteria:

• Patients ≥ 40 years of age;
• Chronic symptomatic HFpEF defined as follows: left ventricular ejection fraction (LVEF) > or = 45% within 6 months prior to screening visit (regardless of the imaging modality);
• No recent change in RAAS inhibitors regimen for at least 1 month before enrolment (excluding changes in oral diuretics);
• NYHA functional class II to IV;
• Evidence of structural heart disease defined by at least 1 of the following echocardiography findings: LV hypertrophy (i.e. septal or posterior wall thickness ≥1.1 cm) or left atrial enlargement (i.e., width ≥3.8 cm, length ≥5.0 cm, area ≥20 cm2, volume ≥55 ml, or volume index ≥29 ml/m2);
• Patients with a diagnosis of acute heart failure (treated with intravenous diuretics) within 12 months before screening; or an NT-proBNP of ≥300 pg/ml if in sinus rhythm, and ≥900 pg/ml if in atrial fibrillation within 30 days before screening (if multiple measurements, consider the highest);

• At least one of the following criteria defining chronic enhanced inflammatory milieu:

  1. Obesity, defined as body mass index (BMI) > 30kg/m2,
  2. Type 2 diabetes according to Diabetes Canada definition (http://guidelines.diabetes.ca/cpg/chapter3), and regardless of therapy,
  3. Evidence of pathological systemic inflammation including: high hs-CRP levels (hs-CRP>2mg/L), or the combination of high neutrophil count and low lymphocyte count (Neutrophil to Lymphocyte Ratio >3) within 30 days before screening (if multiple measurements, consider the higher),
• Subjects with the capacity to provide informed consent.

Exclusion Criteria:

• Any prior measurement of LVEF <40%;
• Patients with a diagnosis of hypertrophic or infiltrative cardiomyopathy;
• Presence of hemodynamically significant valvular heart disease in the opinion of the investigator;
• Presence of active infection within the 3 months prior to visit 1 needing antibiotics (excluding COVID-19);
• Acute decompensated HF, acute coronary syndrome (including myocardial infarction), cardiac surgery, other major cardiovascular surgery, or urgent percutaneous coronary intervention (PCI) within the 3 months prior to visit 1;
• Elective PCI within 30 days prior to visit 1;
• Known or clinically judged significant (i.e., angina with CCS class >2/4) epicardial coronary artery disease (CAD) that has not been revascularized (revascularized CAD is defined by a history of myocardial infraction, percutaneous intervention, or coronary artery bypass grafting);
• Changes renin-angiotensin-aldosterone system (RAAS) inhibitors regimen within 30 days prior to screening visit;
• History of hypersensitivity to colchicine;
• Life-threatening or uncontrolled dysrhythmia, including symptomatic or sustained ventricular tachycardia and atrial fibrillation or atrial flutter with a resting ventricular rate >120 beats per minute;
• Any surgical or medical condition that 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;
• Evidence of hepatic disease as determined by any 1 of the following: serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) values exceeding 3× the upper limit of normal, bilirubin>1.5 mg/dL (>25.65 μmol/L) at baseline visit; or patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease;
• Patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula at baseline visit;
• History or presence of any other disease with a life expectancy of <1 year;
• Patient with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patient with chronic diarrhea;
• Patient with pre-existent progressive neuromuscular disease;
• Patient currently taking colchicine for other indications (mainly chronic indications represented by Familial Mediterranean Fever or gout). There is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrolment;
• Patients currently under long-term steroid medication for a chronic condition, or steroid medication within 30 days before screening;
• Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Positive pregnancy test result at the screening visit, and females of childbearing potential who do not agree to use adequate method of contraception for the duration of the study; acceptable means of birth control include: implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner.