Colchicine in acute heart failure: Rationale and design of a randomized double‐blind placebo‐controlled trial (COLICA)

• Published in: European journal of heart failure Vol. 26; no. 9; pp. 1999 - 2007
• Main Authors: Pascual‐Figal, Domingo, Núñez Villota, Julio, Pérez‐Martínez, Maria Teresa, González‐Juanatey, José Ramón, Taibo‐Urquía, Mikel, Llàcer Iborra, Pau, González‐Martín, Javier, Villar, Sandra, Soler, Meritxel, Mirabet, Sonia, Aimo, Alberto, Riquelme‐Pérez, Alejandro, Anguita Sánchez, Manuel, Martínez‐Sellés, Manuel, Sánchez, Pedro L., Ibáñez, Borja, Bayés‐Genís, Antoni, Martínez, Andrés Ramón, Pérez, Alejandro Riquelme, Bravo, Iris Paula Garrido, López, Alberto Nieto, Pérez, Francisco José Pastor, Villa, Noelia Fernández, Hernández‐Vicente, Alvaro, Núñez, Julio, Mollar, Anna, González‐Juanatey, Jose Ramón, Seijas, Jose, Ibañez, Borja, Taibo, Mikel, Talavera, Sandra Gómez, Álvarez, María López, Viyuela, Alba María Vega, Pérez, Pablo Gil, Balaguer‐Germán, Jorge, Medrado, María José Díez, Martín, Javier González, Fernandez, Laura Morán, García, Juan Carlos López‐Azor, Juan Bagudá, Javier, Cármena, M Dolores García‐Cosio, Delgado Jiménez, Juan F, LLacer, Pau, Manzano, Luis, Ruiz, Raúl, López, Genoveva, Bayes‐Genis, Antoni, Soler, Meritxell, Llibre, Cinta, De Antonio, Marta, Moliner‐Abós, Carlos, Pomares, Antonia, Emdin, Michele, Martinez‐Selles, Manuel, Sousa, Iago, Zataraín, Eduardo, Anguita, Manuel, Sanchez, Pedro Luis
• Format: Journal Article
• Language: English
• Published: Oxford, UK John Wiley & Sons, Ltd 01-09-2024
• Subjects: Colchicine; Heart failure; Inflammation; Randomized controlled trial; Heart failure; Inflammation; Colchicine; Randomized controlled trial
• ISSN: 1388-9842; 1879-0844; 1879-0844
• DOI: 10.1002/ejhf.3300

Aims
Heart failure (HF) elicits a pro‐inflammatory state, which is associated with impaired clinical outcomes, but no anti‐inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin‐1 axis are overactivated during episodes of acute HF. Colchicine, an anti‐inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients.
Methods
COLICA is a multicentre, randomized, double‐blind, placebo‐controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new‐onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time‐averaged proportional change in NT‐proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events.
Conclusion
COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.
Schematic representation of the rationale and design of the COLICA study: acute heart failure (AHF) is associated with an overactivation of the interleukin (IL)‐1 axis and elevated pro‐inflammatory cytokines, which causes cardiac dysfunction and facilitates clinical adverse events. The anti‐inflammatory effect of colchicine, initiated within the first 24 h after AHF presentation, will facilitate clinical stability through such vulnerable period, including lower levels of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and lower rates of worsening heart failure (WHF) at 8 weeks, as compared with placebo.