Cluster and Registry trials Of the Working group of heart failure in Denmark - Are SPironolactone and Eplerenone Comparable Treatments? (CROWD-ASPECT)

The primary objective of the study titled "Cluster and Registry trials Of the Working group of heart failure in Denmark - Are SPironolactone and Eplerenone Comparable Treatments? (CROWD-ASPECT)" is to compare the **efficacy** of spironolactone and eplerenone in reducing the risk of death among patients with heart failure with reduced ejection fraction who are being followed in a heart failure clinic. This comparison is clinically relevant as it aims to determine the most effective aldosterone antagonist for improving survival outcomes in this patient population, potentially guiding treatment decisions and optimizing patient care in heart failure management.

The clinical trial involves participants diagnosed with **heart failure** with a reduced ejection fraction. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants are not considered part of a vulnerable population. The trial focuses on individuals who are registered in the Danish Heart Failure Registry and have claimed at least one prescription for an aldosterone antagonist. The sponsor has not provided information regarding the total number of participants. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria emphasize the inclusion of patients with a specific medical history related to heart failure treatment.

The clinical trial is designed to evaluate the **efficacy** of **spironolactone** and **eplerenone** in patients with **heart failure** and reduced ejection fraction. This study is a randomized, double-blind, controlled trial with a low-intervention classification, as defined by European and Danish authorities. The trial will compare the two aldosterone antagonists, spironolactone and eplerenone, in terms of their impact on the risk of death in patients who are already registered in the Danish Heart Failure Registry and have claimed at least one prescription for an aldosterone antagonist. The primary endpoint is death, while the secondary endpoint includes death or hospitalization for heart failure.

The trial is expected to run from January 1, 2023, to December 31, 2028, with a maximum treatment period of 84 days for each participant. Participants will be involved in the study for the duration of their treatment period, with the possibility of early termination if they experience adverse effects or if they withdraw consent. The study visits will include an initial screening visit to confirm eligibility based on the inclusion criteria, followed by regular follow-up visits to monitor the participants' health status and adherence to the treatment protocol. The end-of-study visit will assess the final outcomes and collect data for analysis.

Participants will be randomly assigned to receive either spironolactone or eplerenone, both administered orally in the form of film-coated tablets. The maximum daily dose for each medication is 50 mg, with a total maximum dose of 126,000 mg over the treatment period. The trial will ensure that all medications are used according to their marketing authorization, and no additional patient assessments are required beyond standard care. Data collection will primarily rely on existing registries, minimizing the need for additional interventions. The study aims to provide valuable insights into the comparative effectiveness of these two treatments in managing heart failure with reduced ejection fraction.

The clinical trial involves the administration of **Spironolactone**, marketed as "Spironolactone 'Accord', filmovertrukne tabletter." This medication is provided in the form of a **film-coated tablet** and is intended for oral administration. The active substance, spironolactone, is of chemical origin. The maximum daily dose is 50 mg, with a total maximum dose of 126,000 mg over a treatment period of 84 days. The trial aims to assess the efficacy of spironolactone in patients with heart failure with reduced ejection fraction, who have an indication for treatment with aldosterone antagonists. The pharmaceutical product is manufactured by Accord Healthcare B.V. and is authorized for use in Denmark.

Another treatment used in the trial is **Eplerenone**, marketed as "Eplerenon 'Stada', filmovertrukne tabletter." Similar to spironolactone, eplerenone is also provided as a **film-coated tablet** for oral administration. The active substance, eplerenone, is of chemical origin. The maximum daily dose is 50 mg, with a total maximum dose of 1,260,000 mg over a treatment period of 84 days. This medication serves as a comparator in the trial, aiming to evaluate its efficacy relative to spironolactone in the same patient population. The product is manufactured by STADA Arzneimittel AG and is authorized for use in Denmark.

Both medications are administered orally, and participant compliance is monitored throughout the trial to ensure adherence to the dosing schedule. The trial does not include any non-experimental treatments such as placebo or standard-of-care therapy, focusing solely on the comparison between spironolactone and eplerenone.

The clinical trial aims to assess the efficacy of **spironolactone** and **eplerenone** in patients with heart failure with reduced ejection fraction. The primary endpoint for evaluating efficacy is the risk of death. A secondary endpoint includes the composite of death or hospitalization for heart failure. These endpoints will be measured and collected through data obtained from the Danish Heart Failure Registry, ensuring that all information is gathered from existing records without additional patient assessments.

The trial is designed as a low-intervention study, with heart failure clinics pre-allocated to use one specific aldosterone antagonist as the first-choice drug. This approach aligns with the marketing authorization of the drugs, and no unapproved drugs or additional patient assessments are involved. The study will utilize registry data to analyze the outcomes, ensuring a comprehensive evaluation of the comparative effectiveness of the two treatments over the maximum treatment period of 84 days.