Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
- Conditions
- Heart Failure With Reduced Ejection Fraction (HFrEF)Sudden Cardiac DeathVentricular ArrhythmiaImplantable Cardioverter Defibrillator (ICD)Beta-blocker TherapyCardiomyopathy
- Interventions
- Registration Number
- NCT06964464
- Lead Sponsor
- University of Rochester
- Brief Summary
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.
- Detailed Description
The Comparative Effectiveness of Carvedilol versus Metoprolol Succinate in Heart Failure Patients with an Implantable Cardioverter Defibrillator (CARVTOP-ICD) study is a prospective, multicenter, open-label, two-arm, randomized clinical trial designed to assess the comparative effectiveness 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 a total of 2,000 participants from 100 sites across the United States, with an initial feasibility phase enrolling 100 participants from 15 sites over 18 months.
The feasibility phase will assess study infrastructure, recruitment, consent processes, medication switching protocols, safety, adherence, and retention. A patient-centered approach, including engagement of caregivers and stakeholders, underpins this phase. Strategies to improve patient and provider participation, address barriers to beta-blocker switching, and ensure diversity in enrollment will be employed. Lessons learned will guide the full-scale study.
Eligible participants must have an ICD implanted for primary prevention of sudden cardiac death due to HFrEF (either ischemic or non-ischemic etiology), be currently treated with metoprolol succinate, and be willing to switch to carvedilol. Participants will be randomized 1:1 to either remain on metoprolol succinate or switch to an equivalent dose of carvedilol, with titration to maximally tolerated doses per protocol. Key exclusion criteria include treatment with any beta-blocker other than metoprolol succinate, systolic blood pressure \<100 mmHg, known intolerance to carvedilol, or inability to comply with the study protocol.
The primary endpoint is the first occurrence of any ICD therapy (appropriate or inappropriate), cardiovascular hospitalization, or cardiovascular death. Secondary endpoints include the burden of ICD shocks, healthcare utilization (including emergency visits and hospitalizations), and quality of life (QoL) measured by the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12), Florida Shock Anxiety Scale (FSAS), and Patient Health Questionnaire-2 (PHQ-2). Tertiary endpoints include specific analyses of ventricular tachyarrhythmias and atrial arrhythmias leading to inappropriate ICD therapies.
Participants will be followed for an average of 3 years. Assessments will be conducted at baseline, weeks 2 and 4, and quarterly thereafter. Study data will include standard of care tests such as cardiac imaging, ICD interrogations, laboratory measures (BNP/NT-proBNP, creatinine, BUN, potassium, sodium), NYHA classification, CV medication data, adverse events, protocol deviations, and patient-reported outcomes.
The study will also assess subgroup responses by sex, age, race/ethnicity, heart failure etiology (ischemic vs non-ischemic), ICD type (ICD vs CRT-D), and degree of LVEF impairment.
This PCORI-funded trial will generate robust, real-world evidence to guide clinical decision-making on beta-blocker choice in HFrEF patients with ICDs, addressing a significant gap in evidence and helping inform personalized treatment strategies to improve clinical and arrhythmic outcomes.
More information can be found at www.carvtop.org
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 2000
- 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
- Enrollment in another clinical trial
- Inability or unwilling to consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metoprolol Succinate Group Metoprolol Succinate Participants in this group will remain on their current treatment with metoprolol succinate. The dose of metoprolol succinate may be titrated to achieve recommended target doses as per the study protocol. The aim is to assess the outcomes associated with continued use of metoprolol succinate in patients with heart failure and an implantable cardioverter defibrillator (ICD). Carvedilol Group Carvedilol Participants in this group will switch from metoprolol succinate to carvedilol at an equivalent dose. The dose of carvedilol will be titrated to the recommended target dose as per the study protocol. The goal is to evaluate the comparative effectiveness of carvedilol compared to metoprolol succinate in reducing cardiovascular events in patients with heart failure and an ICD.
- Primary Outcome Measures
Name Time Method Composite Endpoint: First Occurrence of ICD Therapy, Cardiovascular Hospitalization, or Cardiovascular Death Up to 3 years 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.
- Secondary Outcome Measures
Name Time Method Quality of Life - Florida Shock Anxiety Scale (FSAS) Baseline, Year 1, Year 2, Year 3 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.
Quality of Life - Patient Health Questionnaire-2 (PHQ-2) Baseline, Year 1, Year 2, Year 3 The PHQ-2 is a 2-item screening tool that assesses depressive symptoms, focusing on anhedonia and depressed mood over the past two weeks. Each item is scored from 0 to 3, and the total score is the sum of the two items. Higher scores indicate greater severity of depressive symptoms.
Healthcare Utilization Average of 3 years 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 Average of 3 years Total number of ICD shocks (appropriate and inappropriate).
Quality of Life - Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) Baseline, Year 1, Year 2, Year 3 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.