This prospective, multicenter, open-label, randomized comparative effectiveness trial, titled CARVTOP-ICD, evaluates the impact of carvedilol versus metoprolol succinate in patients with heart failure with reduced ejection fraction (HFrEF) and an implantable cardioverter defibrillator (ICD). The study will enroll 2,000 participants across 100 U.S. sites and includes an 18-month feasibility phase with 100 participants from 15 sites. Eligible participants must be currently treated with metoprolol succinate and willing to switch to carvedilol, with randomization in a 1:1 ratio. Participants will be followed for up to 3 years, with regular assessments including ICD interrogations, medication adherence, healthcare utilization, and quality of life surveys. The primary endpoint is the first occurrence of any ICD therapy (appropriate or inappropriate), cardiovascular (CV) hospitalization, or CV death. Secondary endpoints include ICD shock burden, healthcare utilization, and patient-reported quality of life. The trial aims to provide high-quality comparative data to address clinical equipoise surrounding the two commonly used beta-blockers in HFrEF management.
Age ≥ 18 years
ICD implanted for primary prevention for HFrEF (either ICM or NICM) with remote monitoring capability
Current treatment with metoprolol succinate and willing to switch to carvedilol
LVEF <50% during the past 12 months prior to consent
Unwilling or unable to follow the protocol
Treatment with any other ßB than metoprolol succinate or no ßB treatment
Known prior intolerance or contraindication to carvedilol
Systolic blood pressure <100 mmHg
Parallel
Metoprolol Succinate
DrugMetoprolol succinate is a beta-blocker used for the management of heart failure with reduced ejection fraction (HFrEF). In this study, participants in the metoprolol succinate group will remain on their current treatment regimen with metoprolol succinate. The dose will be titrated to the recommended target dose as per the study protocol. The intervention aims to evaluate the effectiveness of continued use of metoprolol succinate in patients with heart failure and an implantable cardioverter defibrillator (ICD).
Carvedilol
DrugCarvedilol is a non-selective beta-blocker with alpha-blocking activity used in the treatment of heart failure. In this study, participants assigned to the carvedilol group will switch from metoprolol succinate to carvedilol at an equivalent dose. The carvedilol dose will be titrated to recommended target doses according to the study protocol. This intervention aims to compare the effectiveness of carvedilol versus metoprolol succinate in improving clinical outcomes in patients with heart failure and ICDs.
Composite Endpoint: First Occurrence of ICD Therapy, Cardiovascular Hospitalization, or Cardiovascular Death
This composite outcome measures the time to first occurrence of one of the following events: (1) ICD therapy (appropriate or inappropriate shocks or anti-tachycardia pacing), (2) hospitalization due to cardiovascular causes, or (3) cardiovascular death. Only the first event occurring during the study period will be counted per participant.
Healthcare Utilization
Total number of the following events during the study: all-cause hospital admissions, emergency department visits, and unplanned clinic visits. All events will be captured from electronic medical records.
ICD Shock Burden
Total number of ICD shocks (appropriate and inappropriate).
Quality of Life - Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12)
The KCCQ-12 is a 12-item self-administered questionnaire designed to assess the health status and quality of life in patients with heart failure. It evaluates symptoms, physical and social limitations, and overall quality of life. The total score ranges from 0 to 100, with higher scores indicating better health status.
Quality of Life - Florida Shock Anxiety Scale (FSAS)
The FSAS measures anxiety related to the possibility of receiving an ICD shock. It consists of 10 items, each rated on a 5-point Likert scale (1 = not at all, 5 = all of the time). Individual item scores are summed to produce a total score ranging from 10 to 50, with higher scores indicating greater shock-related anxiety.
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University of Rochester
Lead sponsor
Patient-Centered Outcomes Research Institute
Collaborator
