Clinical trial NCT06604611: Colchicine in Patients with Heart Failure with Preserved Ejection Fraction and Inflammation
Official title: Efficacy and Safety of Colchicine in Patients with Heart Failure with Preserved Ejection Fraction and Inflammation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Heart Failure
Heart Failure with Preserved Ejection Fraction (HFPEF)
Chronic Inflammation
Inflammation
Colchicine
Keywords: Heart Failure
Heart Failure with Preserved Ejection Fraction (HFpEF)
Inflammation
Lead sponsor: Chongqing Medical University
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2024-09-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in KCCQ-CS scores
timeFrame: Up to 12 weeks
measure: Change in 6-MWD
timeFrame: Up to 12 weeks
measure: Change in serum CRP levels
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Change in serum NT-proBNP levels
timeFrame: Up to 12 weeks
measure: Change in serum IL-1β levels
timeFrame: Up to 12 weeks
measure: Change in serum IL-6 levels
timeFrame: Up to 12 weeks
measure: Change in serum TNF-α levels
timeFrame: Up to 12 weeks
measure: Change in cardiac structure
timeFrame: Up to 12 weeks
measure: Change in cardiac structure
timeFrame: Up to 12 weeks
measure: Change in cardiac structure
timeFrame: Up to 12 weeks
measure: Change in cardiac function
timeFrame: Up to 12 weeks
measure: Change in cardiac function
timeFrame: Up to 12 weeks
measure: Change in cardiac function
timeFrame: Up to 12 weeks
measure: Change in cardiac function
timeFrame: Up to 12 weeks
measure: Worsening heart failure events
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: First Affiliated Hospital of Chongqing Medical University
name: Dongying Zhang, MD. Ph.D.
role: STUDY_CHAIR
References:
citation: Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022 May 3;145(18):e895-e1032. doi: 10.1161/CIR.0000000000001063. Epub 2022 Apr 1.
citation: Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847. doi: 10.1056/NEJMoa2021372. Epub 2020 Aug 31.
citation: Pascual-Figal D, Nunez J, Perez-Martinez MT, Gonzalez-Juanatey JR, Taibo-Urquia M, Llacer-Iborra P, Delgado J, Villar S, Mirabet S, Aimo A, Riquelme-Perez A, Anguita-Sanchez M, Martinez-Selles M, Noguera-Velasco JA, Ibanez B, Bayes-Genis A. Colchicine in acutely decompensated heart failure: the COLICA trial. Eur Heart J. 2024 Dec 1;45(45):4826-4836. doi: 10.1093/eurheartj/ehae538.