Heart Failure With Reduced Ejection FractionPhase 4NCT07490067
Mechanistic Clinical Trial Comparing the Pharmacokinetics/Pharmacodynamics of Metoprolol in Heart Failure With Reduced Ejection Fraction Patients With Low vs. High Polygenic Score
A Phase 4 study testing Metoprolol Succinate, Beta-Blocker Polygenic Score and Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx) in people with Heart Failure With Reduced Ejection Fraction, run by University of Michigan at 1 site in United States.
Trial summary
The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. 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
- What is being tested?
- Metoprolol Succinate, Beta-Blocker Polygenic Score and Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2026to Jul 2029
- 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
- Heart Failure with Reduced Ejection Fraction (HFrEF)
- Has not taken a beta-blocker within the past 6 months (preferred), or if needed to meet enrollment target, patients that have not taken a beta-blocker in the past 3 months, or only taken a low dose of beta-blocker within the past 6 months (i.e., < 50% of the guideline-recommended HFrEF target dose, or for beta-blockers that are not approved for HFrEF, <50% of the maximum dose)
- Genetic data already available to calculate the polygenic score (e.g., through participation in the Michigan Genomics Initiative (MGI) or other genetic tests) or willingness to provide a deoxyribonucleic acid (DNA) sample for genetic analysis
- White race
- Has been prescribed a stable dose (including no dose) of angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), ARB-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 (SGLT-2) inhibitor, or mineralocorticoid receptor antagonist (MRA) for at least the past 4 weeks
- Has been prescribed a stable dose (including no dose) of diuretic(s) for at least the past 2 weeks
- For women of child-bearing potential: the participant is willing to perform a pregnancy test and use a highly effective contraceptive method for at least 4 weeks prior to the start of metoprolol treatment, during the entire metoprolol treatment period, and for at least 5 days after the discontinuation of metoprolol treatment
- Ability to understand and willing to sign a written informed consent
Who cannot join
- Prior heart transplant or left ventricular assist device (LVAD) or planned within treatment period
- Planned implantation of a pacemaker or Cardiac Resynchronization Therapy (CRT) during treatment period
- Patients with a pacemaker that does not allow their heart rate to change in response to exercise per protocol
- Pregnant
- Systolic blood pressure < 95 millimeters of mercury (mmHg)
- Heart rate < 60 beats per minute
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- Second (Mobitz II)- or third-degree heart block
- Cardiogenic shock
- Patients with acute decompensated heart failure requiring current hospitalization or immediate medical intervention.
- Sick sinus syndrome
- Pheochromocytoma
- Known hypersensitivity to the metoprolol succinate oral tablet used in the trial
- Hypertrophic obstructive cardiomyopathy
- Active myocarditis
- Acute coronary syndrome within the past month
- Active or uncorrected severe mitral or aortic valvular dysfunction
- Patients with known severe congenital heart disease per protocol
- Child-Pugh Class C liver disease
- Patients with end-stage renal disease (ESRD) requiring hemodialysis
- Concomitant disease that prohibits participating in Cardiopulmonary Exercise Test (CPET) per protocol
- Concomitant disease with expected survival less than the duration of the study (e.g., metastatic cancer)
- Current or planned treatment with cardiotoxic medications, including interferons and the cancer therapies per protocol
- Concurrent participation in another clinical trial that may affect participant safety or validity of data collected in this clinical trial
- Inability to take oral medication
- Unwilling or unlikely to adhere to the study procedures, as determined at the discretion of the study team, including but not limited to the following reasons:
- Psychiatric illness or other comorbidities
- Substance abuse
- Social or logistical circumstances
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Jamine Luzman, PharmD, PhD, 734-615-4851, jluzum@med.umich.edu
Jasmine Luzum, PharmD, PhD
About this study
Official title: Personalizing Heart Failure Treatment With Genomics: A Clinical Trial to Understand the Mechanisms and Validate a Polygenic Risk Score for Beta-Blocker Response
The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study.
The hypotheses for this trial are:
- HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score.
- HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score.
- HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.
- Being tested
- Metoprolol Succinate, Beta-Blocker Polygenic Score, Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx)
- Keywords
- Beta-blocker, Polygenic Risk Score, Pharmacokinetic, Pharmacogenomics, Pharmacodynamics, Pharmacogenetic, Cardiac testing
- Medical subject headings
- Genetic Risk Score
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol SuccinateDrug
Also called Lopressor, Toprol-Extended Release (XL)
Participants will be given daily metoprolol and the dose will be titrated up to 200 milligrams daily (over 6-12 weeks) or the maximum tolerated dose. Once this dose is reached treatment will continue for approximately 5-8 months. In addition, participants, will have various visits that include laboratory and cardiac testing at certain time points.
Beta-Blocker Polygenic ScoreDevice
The purpose of the beta-blocker polygenic score is to predict which HFrEF patients will respond better to beta-blocker therapy. It will be used to stratify the patients in the low and high polygenic score groups in the study. There are no post-manufacturing modifications to the score.
Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx)Device
If the participant does not already have genotype data available through Michigan Genomics Initiative (MGI), then this device will be used to genotype DNA sample, which will be used to calculate the polygenic score. There are no post-manufacturing modifications to the device.
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol succinate | Experimental | Treatment will be given for approximately 6 months Receives: Drug: Metoprolol Succinate; Device: Beta-Blocker Polygenic Score; Device: Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Half Maximal Effective Concentration of Change in Exercise-Induced Heart Rate (EC50 of ΔEIHR)
The plasma concentration of s-metoprolol succinate that causes 50% of the change in exercise-induced heart rate.
Measured: Baseline to approximately 6 months
Secondary outcomes (3)
Change in left ventricular ejection fraction (LVEF)
Measured: Baseline to approximately 6 months
Area Under the Curve from 0 to 24 hours s-metoprolol plasma concentration-time curve "at steady state"
Measured: Approximately 6 months
Maximum tolerated dose of metoprolol succinate (total daily dose in milligram)
Measured: Approximately 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2026
- Study startDec 2026 (estimated)
- Primary completionJul 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- Single site; open-label to treatment (metoprolol), but double-blinded to the participants' polygenic score (low vs. high)
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Jasmine Luzum, University of Michigan
- Investigators
- Jasmine Luzum, PharmD, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07490067
- Sponsor's protocol ID
- HUM00266021
- Other IDs
- 1R01HL178410-01
- Status last verified
- Oct 2026
- First submitted
- 18 Mar 2026
- Last updated
- 15 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalizing Heart Failure Treatment With Genomics: A Clinical Trial to Understand the Mechanisms and Validate a Polygenic Risk Score for Beta-Blocker Response
- ClinicalTrials.gov ID
- NCT07490067
- Acronym / sponsor ID
- HUM00266021
- Keywords
- Beta-blocker, Polygenic Risk Score, Pharmacokinetic, Pharmacogenomics, Pharmacodynamics, Pharmacogenetic, Cardiac testing
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 2026 (estimated)
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Jul 2029 (estimated)
- First posted
- 24 Mar 2026 (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.
The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study.
The hypotheses for this trial are:
- HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score.
- HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score.
- HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single site; open-label to treatment (metoprolol), but double-blinded to the participants' polygenic score (low vs. high)
| Arm | Type | Receives |
|---|---|---|
| Metoprolol succinate | Experimental | Drug: Metoprolol Succinate, Device: Beta-Blocker Polygenic Score, Device: Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx)Treatment will be given for approximately 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Heart Failure with Reduced Ejection Fraction (HFrEF)
- Has not taken a beta-blocker within the past 6 months (preferred), or if needed to meet enrollment target, patients that have not taken a beta-blocker in the past 3 months, or only taken a low dose of beta-blocker within the past 6 months (i.e., < 50% of the guideline-recommended HFrEF target dose, or for beta-blockers that are not approved for HFrEF, <50% of the maximum dose)
- Genetic data already available to calculate the polygenic score (e.g., through participation in the Michigan Genomics Initiative (MGI) or other genetic tests) or willingness to provide a deoxyribonucleic acid (DNA) sample for genetic analysis
- White race
- Has been prescribed a stable dose (including no dose) of angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), ARB-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 (SGLT-2) inhibitor, or mineralocorticoid receptor antagonist (MRA) for at least the past 4 weeks
Key exclusion criteria (28 listed)
- Prior heart transplant or left ventricular assist device (LVAD) or planned within treatment period
- Planned implantation of a pacemaker or Cardiac Resynchronization Therapy (CRT) during treatment period
- Patients with a pacemaker that does not allow their heart rate to change in response to exercise per protocol
- Pregnant
- Systolic blood pressure < 95 millimeters of mercury (mmHg)
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 SuccinateAlso: Lopressor, Toprol-Extended Release (XL)Participants will be given daily metoprolol and the dose will be titrated up to 200 milligrams daily (over 6-12 weeks) or the maximum tolerated dose. Once this dose is reached treatment will continue for approximately 5-8 months. In addition, participants, will have various visits that include laboratory and cardiac testing at certain time points. | Drug | Metoprolol succinate |
| Beta-Blocker Polygenic ScoreThe purpose of the beta-blocker polygenic score is to predict which HFrEF patients will respond better to beta-blocker therapy. It will be used to stratify the patients in the low and high polygenic score groups in the study. There are no post-manufacturing modifications to the score. | Device | Metoprolol succinate |
| Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx)If the participant does not already have genotype data available through Michigan Genomics Initiative (MGI), then this device will be used to genotype DNA sample, which will be used to calculate the polygenic score. There are no post-manufacturing modifications to the device. | Device | Metoprolol succinate |
Primary outcome
Half Maximal Effective Concentration of Change in Exercise-Induced Heart Rate (EC50 of ΔEIHR)
Time frame: Baseline to approximately 6 months
The plasma concentration of s-metoprolol succinate that causes 50% of the change in exercise-induced heart rate.
3 secondary outcomes
Change in left ventricular ejection fraction (LVEF)
Time frame: Baseline to approximately 6 months
Area Under the Curve from 0 to 24 hours s-metoprolol plasma concentration-time curve "at steady state"
Time frame: Approximately 6 months
Maximum tolerated dose of metoprolol succinate (total daily dose in milligram)
Time frame: Approximately 6 months
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 15 Oct 2026.
- Individual participant dataSharing planned: No
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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.
Jasmine Luzum, PharmD, PhD principal investigator
University of Michigan
1 site 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, Beta-Blocker Polygenic Score and Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx) in people with Heart Failure With Reduced Ejection Fraction, run by University of Michigan at 1 site 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 8 inclusion and 28 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 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Diamond Thomas (734-615-4532, diamthom@med.umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Half Maximal Effective Concentration of Change in Exercise-Induced Heart Rate (EC50 of ΔEIHR) (time frame: Baseline to approximately 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Oct 2026.