Heart Failure With Reduced Ejection Fraction (HFrEF)Phase 4CARVTOP-ICDNCT06964464
Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
A Phase 4 study testing Metoprolol Succinate and Carvedilol in people with Heart Failure With Reduced Ejection Fraction (HFrEF) and Sudden Cardiac Death, run by University of Rochester at 13 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia
- What is being tested?
- Metoprolol Succinate and Carvedilol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 13 sitesUnited States
- Study dates
- 17 Aug 2025to 1 Jul 2031
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
United States13 sites, 13 recruiting
- Recruiting
Suny Downstate
Brooklyn, New York, 11203
Adam S Budzikowski, MD, 718-270-4147, abudzikowski@downstate.edu
Ann Harris, 718-270-4147, ann.harris@downstate.edu
- Recruiting
New York-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, 11215
Gioia Turitto, MD, 718-780-3626, git9006@nyp.org
Shana Hayes, M.S., cmc9055@nyp.org
- Recruiting
University of Mossouri
Columbia, Missouri, 65212
Brian Bostick, MD, 573-884-1606, bostickb@health.missouri.edu
Charles Donigian, 573-884-9430, donigianc@health.missouri.edu
- Recruiting
Henry Ford Health System
Detroit, Michigan, 48202
Waddah Maskoun, MD, 313-916-2417, wmaskou1@hfhs.org
Briita Wanhala, 313-916-9575, bwanhal1@hfhs.org
- Recruiting
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Ryan Kipp, MD, 608-265-4188, rtkipp@medicine.wisc.edu
Karen Olson, 608-263-1544, kjolson@medicine.wisc.edu
- Recruiting
Creighton University Medical Center
Omaha, Nebraska, 68124
Attila Roka, MD, 402-398-5880, attilaroka@creighton.edu
Lois A. Rasmussen, 402-343-8539, lois.rasmussen@commonspirit.org
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23298
Keyur Shah, MD, 804-828-4571, keyur.shah@vcuhealth.org
Anna Baranova, 804-628-7455, anna.baranova2@vcuhealth.org
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
Amole Ojo, MD, 585-275-4775, amole_ojo@urmc.rochester.edu
Samantha Delmartino, 585-273-3877, samantha_delmartino@urmc.rochester.edu
- Recruiting
AdventHealth Redmond
Rome, Georgia, 30165
Charles Jackson, MD, 706-802-3139, charles.jackson.md@adventhealth.com
Kathy Jones, 706-802-3139, kathy.d.jones@adventhealth.com
- Recruiting
Health University of Utah
Salt Lake City, Utah, 84112
Ravi Ranjan, MD, 801-587-5888, ravi.ranjan@hsc.utah.edu
Audra Eaquinto, 801-646-8073, audra.eaquinto@hsc.utah.edu
- Recruiting
HonorHealth
Scottsdale, Arizona, 85258
Geoffrey Jao, MD, 480-882-7750, gjao@honorhealth.com
Mary Futch Moyer, 480-323-1043, mfutch@honorhealth.com
- Recruiting
AdventHealth Shawnee Mission
Shawnee Mission, Kansas, 66204
Obadah Al Chekakie, MD, 913-676-2558, MObadah.AlChekakie.MD@AdventHealth.com
Megan Kelly, 913-676-2558, Megan.Kelly1@adventhealth.com
- Recruiting
CHRISTUS Trinity Mother Frances Health System
Tyler, Texas, 75701
Joshua Rutland, MD, 903-606-7525, joshua.rutland@christushealth.org
Carol Cushman, 903-606-8846, carol.cushman@christushealth.org
About this study
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.
Read the 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
- Conditions
- Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia, Implantable Cardioverter Defibrillator (ICD), Beta-blocker Therapy, Cardiomyopathy
- Being tested
- Metoprolol Succinate, Carvedilol
- Keywords
- arrhythmia, heart failure, ICD, implantable cardioverter defibrillator, ICD shock, carvedilol, metoprolol succinate, beta-blocker
- Medical subject headings
- Death, Sudden, Cardiac, Cardiomyopathies, Arrhythmias, Cardiac, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol SuccinateDrug
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).
CarvedilolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol Succinate Group | Active comparator | 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). Receives: Drug: Metoprolol Succinate |
| Carvedilol Group | Experimental | 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. Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 3 years
Secondary outcomes (5)
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.
Measured: Average of 3 years
ICD Shock Burden
Total number of ICD shocks (appropriate and inappropriate).
Measured: Average of 3 years
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.
Measured: Baseline, Year 1, Year 2, Year 3
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.
Measured: Baseline, Year 1, Year 2, Year 3
Quality of Life - Patient Health Questionnaire-2 (PHQ-2)
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.
Measured: Baseline, Year 1, Year 2, Year 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2025
- Study start17 Aug 2025
- Primary completion1 Jun 2031 (estimated)
- Study completion1 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection Fraction (HFrEF)Studies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, Mehmet Aktas, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06964464
- Sponsor's protocol ID
- STUDY00010093
- Other IDs
- PLACER-2023C3-33489
- Acronym
- CARVTOP-ICD
- Status last verified
- Sep 2025
- First submitted
- 30 Apr 2025
- Last updated
- 18 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
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.
PubMed 11386263Packer 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.
PubMed 8614419Poole-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.
PubMed 12853193Diamond 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.
PubMed 37656097Ruwald 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.
PubMed 23770172Ruwald 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.
PubMed 23500269Fiuzat 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.
PubMed 22560018
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
- ClinicalTrials.gov ID
- NCT06964464
- Acronym / sponsor ID
- CARVTOP-ICD / STUDY00010093
- Conditions
- Heart Failure With Reduced Ejection Fraction (HFrEF), Sudden Cardiac Death, Ventricular Arrhythmia, Implantable Cardioverter Defibrillator (ICD), Beta-blocker Therapy, Cardiomyopathy
- Keywords
- arrhythmia, heart failure, ICD, implantable cardioverter defibrillator, ICD shock, carvedilol, metoprolol succinate, beta-blocker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Study start
- 17 Aug 2025 (actual)
- Primary completion
- 1 Jun 2031 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 9 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoprolol Succinate Group | Active comparator | Drug: Metoprolol SuccinateParticipants 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 | Experimental | Drug: CarvedilolParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metoprolol SuccinateMetoprolol 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). | Drug | Metoprolol Succinate Group |
| CarvedilolCarvedilol 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. | Drug | Carvedilol Group |
Primary outcome
Composite Endpoint: First Occurrence of ICD Therapy, Cardiovascular Hospitalization, or Cardiovascular Death
Time frame: 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.
5 secondary outcomes
Healthcare Utilization
Time frame: Average of 3 years
ICD Shock Burden
Time frame: Average of 3 years
Quality of Life - Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12)
Time frame: Baseline, Year 1, Year 2, Year 3
Quality of Life - Florida Shock Anxiety Scale (FSAS)
Time frame: Baseline, Year 1, Year 2, Year 3
Quality of Life - Patient Health Questionnaire-2 (PHQ-2)
Time frame: Baseline, Year 1, Year 2, Year 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
- Background: PubMed 11386263Packer 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.
- Background: PubMed 8614419Packer 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.
- Background: PubMed 12853193Poole-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.
- Background: PubMed 37656097Diamond 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.
- Background: PubMed 23770172Ruwald 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.
- Background: PubMed 23500269Ruwald 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.
- Background: PubMed 22560018Fiuzat 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.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metoprolol Succinate and Carvedilol in people with Heart Failure With Reduced Ejection Fraction (HFrEF) and Sudden Cardiac Death, run by University of Rochester at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mehmet Aktas, M.D. (585-275-5391, Mehmet_Aktas@URMC.Rochester.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite Endpoint: First Occurrence of ICD Therapy, Cardiovascular Hospitalization, or Cardiovascular Death (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06964464, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.