Heart Failure, Heart Failure with Preserved Ejection Fraction (HFPEF), Chronic Inflammation, Inflammation, Colchicine
Conditions
Keywords
Heart Failure, Heart Failure with Preserved Ejection Fraction (HFpEF), Inflammation
Brief summary
The main purpose of the CHIPS trial is to evaluate the efficacy and safety of colchicine in heart failure with preserved ejection fraction (HFpEF) patients with inflammation, including the effects of colchicine on circulating inflammatory markers, cardiac structure, cardiac function, clinical symptoms and exercise capacity in HFpEF patients.
Detailed description
HFpEF is a disease with complex pathophysiological mechanisms, and inflammation has been found to be strongly associated with the onset and progression of HFpEF. Anti-inflammatory treatments begin to cut a striking figure in cardiovascular disease therapy. The LoDoCo2 trial showed a significant prognostic improvement of colchicine in patients with chronic coronary artery disease, and the latest COLICA trial, showed that 8 weeks of colchicine treatment significantly reduced levels of circulating inflammatory markers in patients with decompensated heart failure without serious adverse effects. However, at present, the efficacy and safety of colchicine for the treatment of HFpEF remains unclear. The CHIPS trial is a multi-center, randomized, open-label clinical trial. The aim of the study is to evaluate the efficacy and safety of colchicine in patients with heart failure with preserved ejection fraction and inflammation. The investigators proposed to assess changes in KCCQ scores, NT-proBNP levels, echocardiography and plasma inflammatory marker levels in HFpEF patients treated with or without colchicine to evaluate the efficacy of colchicine in HFpEF treatment.
Interventions
The intervention in this study is colchicine, patients randomized to the experimental group will be given oral colchicine 5mg once a day in 12 weeks.
Sponsors
National Natural Science Foundation of China
Dongying Zhang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomly 1:1 allocate into either a colchicine-treated group or a blank control group, and patients included in different centers will be uniformly randomized by the main centre.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Left ventricular ejection fraction measured by echocardiography ≥ 50% * Objective evidence of structural of functional abnormalities measured by echocardiography: 1)LVMI≥95 g/m2 in female and ≥115 g/m2 in male or 2)LAVI greater than 29ml/m2 in sinus rhythm or greater than 40ml/m2 in atrial fibrillation or 3)Average E/e' greater than 14 or 4)TR velocity greater than 2.8 m/s * Patients with elevated NT-proBNP levels 24 hours after discontinuing intravenous diuretics: ≥300 pg/ml in patients with sinus heart rate; ≥600 pg/ml in patients with atrial fibrillation * Both outpatient and admitted patients can be considered for enrollment. All patients must occurred worsening heart failure event within 30 days prior to randomization and a current NYHA cardiac function class II-IV * Patients with CRP levels greater than 2mg/L * Patient agrees to join and signs a written informed consent form
Exclusion criteria
* Received colchicine treatment within one month prior to randomization * Acute coronary syndrome within 3 months prior to randomization, or history of pacemaker implantation, PCI, CABG within 3 months * eGFR less than 25 mL/min/1.73 m2 * Liver function Child-Pugh class B or C * Patient has a history of previous allergy to colchicine or dapagliflozin / empagliflozin * Heart failure due to the following reasons: pericardial disease, pericardial effusion, myocarditis, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and other rare cardiomyopathies such as Fabry disease * Combined diagnosis of gastric ulcer, ulcerative colitis, Crohn disease and other digestive disorders or combined gastrointestinal tumors * Plan to undergo cardiac surgery such as coronary revascularization, radiofrequency ablation of arrhythmias, valve replacement or other surgical procedures * Pregnant or breastfeeding women * The patient who is cognitively impaired and is unable to accurately complete the assessment and completion of the KCCQ scale with the assistance of a physician * Autoimmune diseases such as systemic lupus erythematosus, long-term adrenocorticotropic hormone treatment for other diseases such as Schihan syndrome, or need to accept immunosuppressive drugs and monoclonal antibodies such as IL-1 and IL-6 * Patient with combined active solid tumor or hematological malignancy * Patient comorbidity with other conditions that may be confused with HFpEF symptoms, such as acute exacerbation of COPD * Admission with a well-defined infection (symptoms or pathogenetic evidence of infection, and leukocytes greater than 10\*109/L) * Previously diagnosed with HFrEF (initial assessment of LVEF less than 40%) or diagnosed with LVimpEF
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in KCCQ-CS scores | Up to 12 weeks | Patients were assessed for symptom improvement by Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) |
| Change in 6-MWD | Up to 12 weeks | Improvement in patients exercise capacity assessed by 6-minuet walk distance |
| Change in serum CRP levels | Up to 12 weeks | Change in serum C-reactive protein levels |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum TNF-α levels | Up to 12 weeks | Change in serum tumor necrosis factor-α levels |
| Change in cardiac structure | Up to 12 weeks | Left ventricular mass index (LVMI) measured by echocardiography |
| Change in serum NT-proBNP levels | Up to 12 weeks | Change in serum N-terminal pro-B-type natriuretic peptide levels |
| Worsening heart failure events | Up to 12 weeks | Time to first worsening heart failure events, including hospitalization due to heart failure or intravenous diuretic therapy |
| Change in cardiac function | Up to 12 weeks | Tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography |
| Change in serum IL-1β levels | Up to 12 weeks | Change in serum interleukin-1β levels |
| Change in serum IL-6 levels | Up to 12 weeks | Change in serum interleukin-6 levels |
Countries
China
Contacts
Primary ContactJunlong Chen, MD.
Backup ContactLei Gao, MD.
Outcome results
None listed