Colchicine in Patients with Heart Failure with Preserved Ejection Fraction and Inflammation

Phase 4

Not yet recruiting

• Conditions: Heart Failure; Heart Failure with Preserved Ejection Fraction (HFPEF); Chronic Inflammation; Inflammation; Colchicine
• Interventions: Drug: Colchicine 0.5 MG Oral Tablet Once Daily

• Registration Number: NCT06604611
• Lead Sponsor: Dongying Zhang

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.

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-14
• Study First Submitted QC: 2024-09-17
• Last Update Submitted: 2024-09-17
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19
• Study Start: 2024-10-31
• Primary Completion: 2025-12-31
• Study Completion: 2026-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Colchicine Treatment Group	Colchicine 0.5 MG Oral Tablet Once Daily	This group is intended to include 100 patients, all of the patients will be given 5mg of once-daily the colchicine treatment on top of the SGLT2i treatment

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Change in serum NT-proBNP levels	Up to 12 weeks	Change in serum N-terminal pro-B-type natriuretic peptide levels
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
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 end-diastolic diameter (LVEDD) measured by echocardiography
Change in cardiac function	Up to 12 weeks	Early diastolic mitral annular tissue velocity (e') measured by echocardiography
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

Trial Locations

Locations (1)

The First Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China