Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
CARVTOP-ICD
2 other identifiers
interventional
2,000
1 country
13
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Aug 2025
Longer than P75 for phase_4
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 30, 2025
CompletedFirst Posted
Study publicly available on registry
May 9, 2025
CompletedStudy Start
First participant enrolled
August 17, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2031
September 18, 2025
September 1, 2025
5.8 years
April 30, 2025
September 12, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Up to 3 years
Secondary Outcomes (5)
Healthcare Utilization
Average of 3 years
ICD Shock Burden
Average of 3 years
Quality of Life - Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12)
Baseline, Year 1, Year 2, Year 3
Quality of Life - Florida Shock Anxiety Scale (FSAS)
Baseline, Year 1, Year 2, Year 3
Quality of Life - Patient Health Questionnaire-2 (PHQ-2)
Baseline, Year 1, Year 2, Year 3
Study Arms (2)
Metoprolol Succinate Group
ACTIVE COMPARATORParticipants 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
EXPERIMENTALParticipants 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.
Interventions
Metoprolol 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 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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
HonorHealth
Scottsdale, Arizona, 85258, United States
AdventHealth Redmond
Rome, Georgia, 30165, United States
AdventHealth Shawnee Mission
Shawnee Mission, Kansas, 66204, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
University of Mossouri
Columbia, Missouri, 65212, United States
Creighton University Medical Center
Omaha, Nebraska, 68124, United States
Suny Downstate
Brooklyn, New York, 11203, United States
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, 11215, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
CHRISTUS Trinity Mother Frances Health System
Tyler, Texas, 75701, United States
Health University of Utah
Salt Lake City, Utah, 84112, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Related Publications (7)
Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL; Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. doi: 10.1056/NEJM200105313442201.
PMID: 11386263BACKGROUNDPacker M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996 May 23;334(21):1349-55. doi: 10.1056/NEJM199605233342101.
PMID: 8614419BACKGROUNDPoole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A; Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003 Jul 5;362(9377):7-13. doi: 10.1016/S0140-6736(03)13800-7.
PMID: 12853193BACKGROUNDDiamond A, Goldenberg I, Younis A, Goldenberg I, Sampath R, Kutyifa V, Chen AY, McNitt S, Polonsky B, Steinberg JS, Zareba W, Aktas MK. Effect of Carvedilol vs Metoprolol on Atrial and Ventricular Arrhythmias Among Implantable Cardioverter-Defibrillator Recipients. JACC Clin Electrophysiol. 2023 Oct;9(10):2122-2131. doi: 10.1016/j.jacep.2023.06.009. Epub 2023 Aug 30.
PMID: 37656097BACKGROUNDRuwald MH, Abu-Zeitone A, Jons C, Ruwald AC, McNitt S, Kutyifa V, Zareba W, Moss AJ. Impact of carvedilol and metoprolol on inappropriate implantable cardioverter-defibrillator therapy: the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy). J Am Coll Cardiol. 2013 Oct 8;62(15):1343-50. doi: 10.1016/j.jacc.2013.03.087. Epub 2013 Jun 13.
PMID: 23770172BACKGROUNDRuwald MH, Ruwald AC, Jons C, Alexis J, McNitt S, Zareba W, Moss AJ. Effect of metoprolol versus carvedilol on outcomes in MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy). J Am Coll Cardiol. 2013 Apr 9;61(14):1518-26. doi: 10.1016/j.jacc.2013.01.020.
PMID: 23500269BACKGROUNDFiuzat M, Wojdyla D, Kitzman D, Fleg J, Keteyian SJ, Kraus WE, Pina IL, Whellan D, O'Connor CM. Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial. J Am Coll Cardiol. 2012 Jul 17;60(3):208-15. doi: 10.1016/j.jacc.2012.03.023. Epub 2012 May 2.
PMID: 22560018BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor - Department of Medicine, Cardiology (SMD)
Study Record Dates
First Submitted
April 30, 2025
First Posted
May 9, 2025
Study Start
August 17, 2025
Primary Completion (Estimated)
June 1, 2031
Study Completion (Estimated)
July 1, 2031
Last Updated
September 18, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share
Individual participant data will not be shared for this study due to privacy concerns and the need to protect patient confidentiality. We will ensure that all results are reported in aggregate form while maintaining participant anonymity.