Comparative Efficacy of Carvedilol and Metoprolol Succinate in Heart Failure Patients with Reduced Ejection Fraction: A Cluster and Registry Trial

The primary objective of the CROWD-COMPARE study is to evaluate the **efficacy** of Carvedilol and Metoprolol succinate in patients with **heart failure** with reduced ejection fraction. This evaluation focuses on comparing the impact of these beta-blockers on all-cause mortality or the first hospitalization due to worsening heart failure. This is clinically relevant as it aims to determine the most effective treatment option for improving patient outcomes in this population, potentially guiding therapeutic decisions in heart failure management.

The clinical trial focuses on patients diagnosed with **heart failure** with reduced ejection fraction, specifically those registered in the Danish Heart Failure Registry. The study population includes both male and female participants, with an age range that encompasses adults and the elderly. The trial does not involve a vulnerable population. Participants are selected based on their registration in the registry and their history of claiming at least one prescription for either Carvedilol or Metoprolol succinate. 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 study aims to evaluate the efficacy of these beta-blockers on all-cause mortality or first hospitalization for worsening heart failure.

The clinical trial is designed to evaluate the efficacy of **Carvedilol** and **Metoprolol succinate** in patients with **heart failure** with reduced ejection fraction. This trial is a randomized, double-blind, controlled study, aiming to compare the effects of these two beta-blockers on all-cause mortality or first hospitalization for worsening heart failure. The trial is expected to run from May 2023 to October 2029, with a maximum treatment period of 48 weeks for each participant. Participants will be selected based on their registration in the Danish Heart Failure Registry and must have claimed at least one prescription for either Carvedilol or Metoprolol succinate.

The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor health status and medication adherence, and an end-of-study visit to assess the primary and secondary endpoints. The primary endpoint is a combined measure of all-cause mortality or first hospitalization for worsening heart failure. Secondary endpoints include all-cause mortality and the combined endpoint stratified by heart rhythm. Participants are expected to be involved in the study for the full duration unless they experience adverse effects, withdraw consent, or if the study is terminated early for any reason.

Throughout the trial, participants will receive either Metoprololsuccinat AL 190 mg prolonged-release tablets or Carvedilol Mylan 25 mg film-coated tablets, administered orally. The maximum daily doses are 190 mg for Metoprolol succinate and 50 mg for Carvedilol. The trial is categorized as low-intervention, aligning with international guidelines for beta-blocker treatment in heart failure patients. The study's design ensures rigorous monitoring and data collection to provide robust evidence on the comparative effectiveness of these treatments in the specified patient population.

The clinical trial involves the administration of two experimental medications to evaluate their efficacy in patients with **heart failure** with reduced ejection fraction. The first medication is **Metoprolol succinate**, marketed under the name Metoprololsuccinat AL 190 mg Retardtabletten. This medication is formulated as a **prolonged-release tablet** and is administered orally. The maximum daily dose is 190 mg, and the treatment period extends up to 48 weeks. The active substance, metoprolol succinate, is of chemical origin and is classified under the ATC code C07AB02. The medication is produced by ALIUD PHARMA GMBH and is not a pediatric formulation.

The second experimental medication is **Carvedilol**, marketed as Carvedilol Mylan 25 mg, filmomhulde tabletten. This medication is provided as a **film-coated tablet** and is also administered orally. The maximum daily dose for carvedilol is 50 mg, with a treatment duration of up to 48 weeks. The active substance, carvedilol, is of chemical origin and is classified under the ATC code C07AG02. This medication is manufactured by MYLAN PHARMACEUTICALS LIMITED and is not intended for pediatric use.

Both medications are used as test treatments in the trial, with no additional non-experimental treatments such as placebo or comparator treatments being employed. The trial aims to compare the efficacy of these two beta-blockers in reducing all-cause mortality or first hospitalization for worsening heart failure. Participant compliance with the dosing schedule will be monitored throughout the study period to ensure adherence to the prescribed treatment regimen.

The efficacy of the clinical trial titled "Cluster and Registry trial Of the Working group of heart failure in Denmark. Are CarvedilOl and Metoprolol succinate comPArable treatments in heart failure patients with Reduced Ejection fraction" will be assessed by evaluating the impact of **Carvedilol** and **Metoprolol succinate** on all-cause mortality or first hospitalization for worsening heart failure in patients with heart failure with reduced ejection fraction. The primary endpoint is a combined measure of all-cause mortality or first hospitalization for worsening heart failure. Secondary endpoints include all-cause mortality and a combined endpoint of all-cause mortality or first hospitalization for worsening heart failure, analyzed according to heart rhythm (sinus rhythm or atrial fibrillation/flutter).