Efficacy of Colchicine in Treating Inflammatory Cardiomyopathy: A Single-Blinded, Randomized, Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of colchicine compared to placebo in patients with **inflammatory cardiomyopathy** after a treatment period of 6 months. The study aims to determine if a larger proportion of patients receiving optimal medical therapy (OMT) plus colchicine will achieve the primary endpoint compared to those in the placebo group. This is clinically relevant as it may provide evidence for colchicine as an effective treatment option, potentially improving patient outcomes in this condition.

Secondary objectives include assessing whether the MCGV status (positive or negative) can independently influence the outcome of patients with inflammatory cardiomyopathy after a minimum follow-up of 6 months. Additionally, the study seeks to identify baseline variables that are independently associated with patient outcomes. These objectives are important for understanding the factors that may affect disease progression and treatment response, thereby guiding personalized treatment strategies.

The clinical trial focuses on patients diagnosed with **inflammatory cardiomyopathy**. The study population includes both male and female participants aged 18 years and older. The sponsor has not provided the total number of participants. Participants were selected based on specific inclusion criteria, such as evidence of myocardial inflammation on CMRI or FDG-PET, and the presence of certain cardiac symptoms or conditions, including a high burden of premature ventricular contractions (PVCs), reduced left ventricular ejection fraction (LVEF), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) or B-type natriuretic peptide (BNP) levels, and persistent high-sensitivity troponin levels. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity were highlighted in the selection process.

The clinical trial is designed as a **single-blinded randomized controlled trial** to evaluate the efficacy of **colchicine** in treating patients with **inflammatory cardiomyopathy**. The trial will compare the outcomes of patients receiving colchicine in addition to optimal medical therapy (OMT) against those receiving a placebo. The primary objective is to assess the proportion of patients who are alive and free from any clinical or arrhythmic worsening, as well as imaging outcomes, after a treatment period of six months. The trial is expected to conclude by December 2027, with recruitment starting in October 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 years or older) and evidence of myocardial inflammation. Follow-up visits will occur periodically to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will evaluate the primary and secondary endpoints, including changes in left ventricular ejection fraction and quality of life assessments.

The expected duration of participant involvement is six months, corresponding to the maximum treatment period. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial will employ oral administration of the investigational product, with a maximum daily dose of 3 mg of colchicine. The study will ensure rigorous monitoring and data collection to achieve its objectives and contribute valuable insights into the management of inflammatory cardiomyopathy.

The clinical trial involves the administration of **Colchicine**, marketed under the name "COLCHICINA LIRCA 1 mg compresse." This experimental medication is provided in the form of a **tablet** and is intended for oral administration. The active substance, **colchicine**, is of chemical origin. The maximum daily dose is set at 3 mg, with a total dose of 1 mg per administration. The treatment period is limited to a maximum of 6 months. The pharmaceutical product is manufactured by ACARPIA FARMACEUTICI S.R.L and is authorized for use in Italy. The trial aims to evaluate the efficacy of colchicine in treating patients with cardiomyopathy with myocarditis, specifically chronic inflammatory cardiomyopathy.

The study also includes a **placebo** comparator, which is a tablet composed of lactose, sucrose, arabic gum, and magnesium stearate. This placebo is administered orally, mirroring the administration route of the experimental medication. The placebo is designed to match the experimental treatment in appearance and administration schedule, ensuring blinding of participants and investigators. The maximum daily dose and treatment period for the placebo are identical to those of the colchicine tablets, with a maximum daily dose of 3 mg and a treatment duration of up to 6 months. The placebo serves as a control to assess the efficacy of colchicine in the study population.

The efficacy of colchicine in treating patients with chronic inflammatory cardiomyopathy will be assessed through a single-blinded randomized controlled trial. The primary endpoint is the proportion of patients who are alive and free of any worsening in clinical, arrhythmic burden, and imaging outcomes, while also showing signs of improvement in imaging or arrhythmic outcomes at 6 months from randomization. Clinical worsening is defined by events such as cardiac death, hospitalization for worsening heart failure or arrhythmic events, and the occurrence of sustained ventricular tachycardia. Worsening arrhythmic burden includes a 50% increase in premature ventricular contraction (PVC) burden on ECG ambulatory monitoring, a 30% increase in non-sustained ventricular tachycardia (NSVT), or any sustained ventricular tachycardia (SVT) recorded during follow-up. Worsening imaging outcomes are identified by a reduction in left ventricular ejection fraction (LVEF) greater than 10% on follow-up echocardiogram or CMRI, or new areas of edema on CMRI or FDG-PET.

Secondary endpoints include the absolute change in LVEF on echocardiogram and CMRI at 6 months, the proportion of patients with LVEF less than 55% or left ventricular dilation on CMRI, and a composite endpoint of time to first event such as all-cause death, heart transplantation, or long-term left ventricular assist device implantation. Additional secondary endpoints involve mortality, time to hospitalization for heart failure or ventricular arrhythmias, and changes in quality of life assessed by the EuroQoL 5-dimension, 5-level questionnaire and the Kansas City Cardiomyopathy Questionnaire. The need to initiate an immunosuppressive drug is also evaluated. Efficacy assessments will be conducted at baseline and at the 6-month follow-up, utilizing validated imaging techniques and patient-reported outcomes to ensure comprehensive evaluation of treatment effects.