Heart Failure With Preserved Ejection FractionPhase 4BLOCK HFpEFNCT04434664
BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in HFpEF
A Phase 4 study testing Amlodipine Besylate and Metoprolol Succinate in people with Heart Failure With Preserved Ejection Fraction and Hypertension, run by University of Pennsylvania at 1 site in United States.
Trial summary
Heart failure with preserved ejection fraction (HFpEF) is a critical public health problem. Heart failure (HF) affects over 5 million adults in the United States (US), and is a major source of morbidity, mortality, and impaired quality of life. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Hypertension
- What is being tested?
- Amlodipine Besylate and Metoprolol Succinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 20 Dec 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults age 18-90 years
- Diagnosis of hypertension defined by at least two of the following: A) ICD-9 (401.0-404.91) or ICD-10 (I10-I13) codes signifying hypertension; B) Treatment with antihypertensive medication other than a loop diuretic for at least two months; C) History of previous blood pressure readings ≥130/80 mmHg at two separate office visits
- Stable antihypertensive therapy; defined as no changes in antihypertensive medications in the preceding 30 days
- A diagnosis of heart failure
- LV ejection fraction >50%
- Elevated filling pressures defined by at least one of the following criteria: A) Mitral E/e' ratio (lateral or septal) >8 with low e' velocity (septal e' <7 cm/s or lateral e' <10 cm/s) and at least one of the following: a. Enlarged left atrium (LA volume index >34 ml/m2); b. Chronic loop diuretic use for management of symptoms; c. Elevated natriuretic peptides (BNP levels >100 ng/L or NT-proBNP levels >300 ng/L); B) Mitral E/e' ratio (lateral or septal) >14; C) Previously elevated invasively determined filling pressures based on one of the following criteria: a. Resting LVEDP >16 mmHg; b. Mean PCWP >12 mmHg; c. PCWP or LVEDP ≥25 mmHg with exercise; D) Previous acutely decompensated heart failure requiring IV diuretics;
Who cannot join
- Systolic BP meeting any of the following criteria: A) Current office systolic BP <100 mmHg; B) Current office systolic BP 100-119 mmHg if not receiving treatment with an antihypertensive agent or if holding antihypertensive medication prior to randomization would be clinically contraindicated, as per the investigator's clinical judgement; C) Current office systolic BP ≥180 mmHg if not receiving treatment with a CCB or β-blocker, or ≥160 mmHg if already receiving a CCB and/or β-blocker prior to the pre-randomization wash-out period; D) Orthostatic hypotension defined as >20 mmHg decline in office systolic BP 3-5 minutes following the transition from sitting to standing position
- Resting heart rate <50 or >100 bpm
- Contraindication to withholding CCB or β-blocker therapy (e.g. use of non-dihydropyridine CCB [diltiazem or verapamil] or β-blocker for rate control for atrial fibrillation) as per the investigator's clinical judgement
- Children, fetuses, neonates, prisoners, and pregnant women (women of childbearing age will undergo a pregnancy test during the screening visit) are not included in this research study.
- Inability/unwillingness to exercise
- Any the following echocardiographic findings: A) LV ejection fraction <45% on any prior echocardiogram, unless it was in the setting of uncontrolled atrial fibrillation; B) Hypertrophic, infiltrative, or inflammatory cardiomyopathy; C) Clinically significant pericardial disease, as per investigator judgment; D) Moderate or greater left-sided valvular disease, any degree of mitral stenosis, or prosthetic mitral valve; E) Severe right-sided valvular disease; F) Severe right ventricular dysfunction
Show all 12Show fewer
- Active coronary artery disease, defined as any of the following: A) Acute coronary syndrome or coronary intervention in the past 2 months; B) Ischemia on stress testing without either subsequent revascularization or a subsequent angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgement
- Clinically significant lung disease, defined as any of the following: A) Chronic Obstructive Pulmonary Disease meeting GOLD criteria stage III or greater; B) Treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease; C) The use of daytime supplemental oxygen
- Primary pulmonary arteriopathy
- eGFR <30 mL/min/1.73m2
- Any medical condition that, under the investigator's discretion, will interfere with safe completion of the study or validity of the endpoint assessments
- Known history of an allergy or clinically significant sensitivity (as determined by the investigator) to either amlodipine besylate or metoprolol succinate
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in Heart Failure With Preserved Ejection Fraction (BLOCK HFpEF) Trial
Heart failure with preserved ejection fraction (HFpEF) is a critical public health problem. Heart failure (HF) affects over 5 million adults in the United States (US), and is a major source of morbidity, mortality, and impaired quality of life. Approximately half of individuals with HF have a preserved left ventricular (LV) ejection fraction (EF), termed HF with preserved EF (HFpEF). While there are several effective pharmacologic therapies for HF with reduced ejection fraction (HFrEF), none have been identified for HFpEF. Hypertension, which is present in approximately 80% of individuals with HFpEF, is the foremost modifiable risk factor for the development and progression of HFpEF. Despite the clinical importance of hypertension in HFpEF, there is limited information on how common antihypertensive agents, particularly calcium channel blockers (CCBs) and β-blockers, effect pathophysiologic mechanisms of HFpEF. This is a mechanistic investigation of the role of dihydropyridine CCBs compared to β-blockers (commonly used antihypertensive agents in clinical practice) in targeting key physiologic abnormalities in HFpEF.
- Being tested
- Amlodipine Besylate, Metoprolol Succinate
- Keywords
- Calcium channel blocker, Beta-blocker
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amlodipine BesylateDrug
The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period
Metoprolol SuccinateDrug
The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period
| Study group | Role | What they receive |
|---|---|---|
| Amlodipine besylate | Active comparator | Initial dose 5mg (1 capsule) daily, titrated up to 10mg (2 capsules) daily for a home systolic BP ≥135 mmHg and heart rate ≥50 bpm after the first week of use Receives: Drug: Amlodipine Besylate |
| Metoprolol succinate | Active comparator | Initial dose 100mg (1 capsule) daily, titrated up to 200mg (2 capsules) daily for a home systolic BP ≥135 mmHg and heart rate ≥50 bpm after the first week of use Receives: Drug: Metoprolol Succinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Home Systolic Blood Pressure
The difference in home systolic blood pressure between treatments was determined using a single summary value per participant per intervention period, calculated as the mean of all available home systolic BP readings obtained during the final week of each intervention period. Home BP monitoring was performed using the same validated device model (Microlife BP 3MX1-4 WatchBP Home N), with three consecutive measurements taken in the morning and evening each day over the seven-day period.
Measured: Measured during the last week of each of the two 4-week intervention phases
Secondary outcomes (10)
Difference in Home Diastolic Blood Pressure
The difference in home diastolic blood pressure between treatments was determined using a single summary value per participant per intervention period, calculated as the mean of all available home diastolic BP readings obtained during the final week of each intervention period. Home BP monitoring was performed using the same validated device model (Microlife BP 3MX1-4 WatchBP Home N), with three consecutive measurements taken in the morning and evening each day over the seven-day period.
Measured: Measured during the last week of each of the two 4-week intervention phases
Difference in Office Systolic Blood Pressure
Blood pressure will be measured at rest with a validated oscillometric device (Uscom BP+/UM-211).
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Office Diastolic Blood Pressure
Blood pressure will be measured at rest with a validated oscillometric device (Uscom BP+/UM-211).
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Peak Oxygen Consumption (VO2) During a Maximal Exercise Test
We will use a supine cycle ergometer in conjunction with expired gas analysis to assess oxygen consumption (VO2) during exercise. Subjects will perform a maximal exertion-limited exercise test using a graded-exercise protocol.
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Quality of Life
Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire. The responses are categorized under 3 subscales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100. The total score will be calculated as the mean of the three subscale scores. A mean score of 100 represents the least symptoms and 0 represents the worst symptoms.
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Systemic Vasodilatory Response to Exercise
Systemic vascular resistance (SVR) will be calculated at rest and at peak exercise as mean arterial pressure / cardiac output. Systemic vasodilatory reserve will be measured as the percentage reduction in SVR during exercise, relative to SVR at rest ([rest SVR - peak exercise SVR] / rest SVR) x 100%.
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Arterial Wave Reflections
Arterial wave reflections will be assessed using radial artery pressure waveforms obtained with a high-fidelity applanation tonometer. Waveforms will be calibrated using brachial mean and diastolic blood pressure. Forward and backward pressure wave components will be derived using wave separation analysis, and arterial wave reflection magnitude will be quantified as the ratio of backward to forward pressure wave amplitudes (unitless ratio). Change from baseline will be reported.
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Large Artery Stiffness
Large artery stiffness will be assessed by measuring carotid-femoral pulse wave velocity using arterial applanation tonometry. Pulse wave velocity will be calculated as the distance between the carotid and femoral recording sites divided by the transit time of the arterial pressure waveform.
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Left Ventricular Filling Pressure
We will assess the ratio of early diastolic mitral inflow velocity (E) to mitral annular tissue velocity (e'; a surrogate of LV filling pressures) on echocardiography
Measured: Measured at the end of each of the two 4-week intervention phases
Difference in Myocardial Strain
Left ventricular systolic function will be assessed by global longitudinal myocardial strain measured using two-dimensional speckle-tracking echocardiography. Strain will be calculated as the peak systolic percentage change in myocardial length from end-diastole to end-systole, expressed as a percentage.
Measured: Measured at the end of each of the two 4-week intervention phases
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2020
- Study start1 Dec 2021
- Primary completion3 Dec 2024
- Study completion20 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jordana Cohen, MD, MSCE, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04434664
- Sponsor's protocol ID
- 833517
- Acronym
- BLOCK HFpEF
- Status last verified
- Jan 2026
- First submitted
- 10 Jun 2020
- Last updated
- 30 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cohen JB, Schrauben SJ, Zhao L, Basso MD, Cvijic ME, Li Z, Yarde M, Wang Z, Bhattacharya PT, Chirinos DA, Prenner S, Zamani P, Seiffert DA, Car BD, Gordon DA, Margulies K, Cappola T, Chirinos JA. Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone. JACC Heart Fail. 2020 Mar;8(3):172-184. doi: 10.1016/j.jchf.2019.09.009. Epub 2020 Jan 8.
PubMed 31926856Chirinos JA, Kips JG, Jacobs DR Jr, Brumback L, Duprez DA, Kronmal R, Bluemke DA, Townsend RR, Vermeersch S, Segers P. Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis). J Am Coll Cardiol. 2012 Nov 20;60(21):2170-7. doi: 10.1016/j.jacc.2012.07.054. Epub 2012 Oct 24.
PubMed 23103044Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 1: pressure and flow measurements and basic principles of wave conduction and reflection. Hypertension. 2010 Oct;56(4):555-62. doi: 10.1161/HYPERTENSIONAHA.110.157321. Epub 2010 Aug 23.
PubMed 20733089Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 2: arterial pressure-flow and pressure-volume relations in humans. Hypertension. 2010 Oct;56(4):563-70. doi: 10.1161/HYPERTENSIONAHA.110.157339. Epub 2010 Aug 23.
PubMed 20733088Zamani P, Rawat D, Shiva-Kumar P, Geraci S, Bhuva R, Konda P, Doulias PT, Ischiropoulos H, Townsend RR, Margulies KB, Cappola TP, Poole DC, Chirinos JA. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation. 2015 Jan 27;131(4):371-80; discussion 380. doi: 10.1161/CIRCULATIONAHA.114.012957. Epub 2014 Dec 22.
PubMed 25533966Zamani P, Tan V, Soto-Calderon H, Beraun M, Brandimarto JA, Trieu L, Varakantam S, Doulias PT, Townsend RR, Chittams J, Margulies KB, Cappola TP, Poole DC, Ischiropoulos H, Chirinos JA. Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction. Circ Res. 2017 Mar 31;120(7):1151-1161. doi: 10.1161/CIRCRESAHA.116.309832. Epub 2016 Dec 7.
PubMed 27927683Muntner P, Shimbo D, Carey RM, Charleston JB, Gaillard T, Misra S, Myers MG, Ogedegbe G, Schwartz JE, Townsend RR, Urbina EM, Viera AJ, White WB, Wright JT Jr. Measurement of Blood Pressure in Humans: A Scientific Statement From the American Heart Association. Hypertension. 2019 May;73(5):e35-e66. doi: 10.1161/HYP.0000000000000087.
PubMed 30827125White WB, Krishnan S, Giacco S, Mallareddy M. Effects of metoprolol succinate extended release vs. amlodipine besylate on the blood pressure, heart rate, and the rate-pressure product in patients with hypertension. J Am Soc Hypertens. 2008 Sep-Oct;2(5):378-84. doi: 10.1016/j.jash.2008.03.002. Epub 2008 Jun 5.
PubMed 20409919Cohen JB, Hossain A, Chittams J, Zhao M, Afable J, Greenip A, Maynard H, Pourmussa B, Prenner SB, Selvaraj S, Townsend RR, Zamani P, Chirinos JA. Calcium Channel Blockade Versus beta-Blockade for Hypertension in Heart Failure With Preserved Ejection Fraction: A Randomized Crossover Trial. Hypertension. 2026 Jul;83(7):e26801. doi: 10.1161/HYPERTENSIONAHA.126.26801. Epub 2026 May 15.
PubMed 42137945
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in Heart Failure With Preserved Ejection Fraction (BLOCK HFpEF) Trial
- ClinicalTrials.gov ID
- NCT04434664
- Acronym / sponsor ID
- BLOCK HFpEF / 833517
- Keywords
- Calcium channel blocker, Beta-blocker
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 3 Dec 2024 (actual)
- Study completion
- 20 Dec 2024 (actual)
- First posted
- 17 Jun 2020 (actual)
- Results
- Posted 30 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heart failure with preserved ejection fraction (HFpEF) is a critical public health problem. Heart failure (HF) affects over 5 million adults in the United States (US), and is a major source of morbidity, mortality, and impaired quality of life. Approximately half of individuals with HF have a preserved left ventricular (LV) ejection fraction (EF), termed HF with preserved EF (HFpEF). While there are several effective pharmacologic therapies for HF with reduced ejection fraction (HFrEF), none have been identified for HFpEF. Hypertension, which is present in approximately 80% of individuals with HFpEF, is the foremost modifiable risk factor for the development and progression of HFpEF. Despite the clinical importance of hypertension in HFpEF, there is limited information on how common antihypertensive agents, particularly calcium channel blockers (CCBs) and β-blockers, effect pathophysiologic mechanisms of HFpEF. This is a mechanistic investigation of the role of dihydropyridine CCBs compared to β-blockers (commonly used antihypertensive agents in clinical practice) in targeting key physiologic abnormalities in HFpEF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amlodipine besylate | Active comparator | Drug: Amlodipine BesylateInitial dose 5mg (1 capsule) daily, titrated up to 10mg (2 capsules) daily for a home systolic BP ≥135 mmHg and heart rate ≥50 bpm after the first week of use |
| Metoprolol succinate | Active comparator | Drug: Metoprolol SuccinateInitial dose 100mg (1 capsule) daily, titrated up to 200mg (2 capsules) daily for a home systolic BP ≥135 mmHg and heart rate ≥50 bpm after the first week of use |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults age 18-90 years
- Diagnosis of hypertension defined by at least two of the following: A) ICD-9 (401.0-404.91) or ICD-10 (I10-I13) codes signifying hypertension; B) Treatment with antihypertensive medication other than a loop diuretic for at least two months; C) History of previous blood pressure readings ≥130/80 mmHg at two separate office visits
- Stable antihypertensive therapy; defined as no changes in antihypertensive medications in the preceding 30 days
- A diagnosis of heart failure
- LV ejection fraction >50%
Key exclusion criteria (12 listed)
- Systolic BP meeting any of the following criteria: A) Current office systolic BP <100 mmHg; B) Current office systolic BP 100-119 mmHg if not receiving treatment with an antihypertensive agent or if holding antihypertensive medication prior to randomization would be clinically contraindicated, as per the investigator's clinical judgement; C) Current office systolic BP ≥180 mmHg if not receiving treatment with a CCB or β-blocker, or ≥160 mmHg if already receiving a CCB and/or β-blocker prior to the pre-randomization wash-out period; D) Orthostatic hypotension defined as >20 mmHg decline in office systolic BP 3-5 minutes following the transition from sitting to standing position
- Resting heart rate <50 or >100 bpm
- Contraindication to withholding CCB or β-blocker therapy (e.g. use of non-dihydropyridine CCB [diltiazem or verapamil] or β-blocker for rate control for atrial fibrillation) as per the investigator's clinical judgement
- Children, fetuses, neonates, prisoners, and pregnant women (women of childbearing age will undergo a pregnancy test during the screening visit) are not included in this research study.
- Inability/unwillingness to exercise
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 |
|---|---|---|
| Amlodipine BesylateThe interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period | Drug | Amlodipine besylate |
| Metoprolol SuccinateThe interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period | Drug | Metoprolol succinate |
Primary outcome
Difference in Home Systolic Blood Pressure
Time frame: Measured during the last week of each of the two 4-week intervention phases
The difference in home systolic blood pressure between treatments was determined using a single summary value per participant per intervention period, calculated as the mean of all available home systolic BP readings obtained during the final week of each intervention period. Home BP monitoring was performed using the same validated device model (Microlife BP 3MX1-4 WatchBP Home N), with three consecutive measurements taken in the morning and evening each day over the seven-day period.
10 secondary outcomes
Difference in Home Diastolic Blood Pressure
Time frame: Measured during the last week of each of the two 4-week intervention phases
Difference in Office Systolic Blood Pressure
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Office Diastolic Blood Pressure
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Peak Oxygen Consumption (VO2) During a Maximal Exercise Test
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Quality of Life
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Systemic Vasodilatory Response to Exercise
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Arterial Wave Reflections
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Large Artery Stiffness
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Left Ventricular Filling Pressure
Time frame: Measured at the end of each of the two 4-week intervention phases
Difference in Myocardial Strain
Time frame: Measured at the end of each of the two 4-week intervention phases
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 31926856Cohen JB, Schrauben SJ, Zhao L, Basso MD, Cvijic ME, Li Z, Yarde M, Wang Z, Bhattacharya PT, Chirinos DA, Prenner S, Zamani P, Seiffert DA, Car BD, Gordon DA, Margulies K, Cappola T, Chirinos JA. Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone. JACC Heart Fail. 2020 Mar;8(3):172-184. doi: 10.1016/j.jchf.2019.09.009. Epub 2020 Jan 8.
- Background: PubMed 23103044Chirinos JA, Kips JG, Jacobs DR Jr, Brumback L, Duprez DA, Kronmal R, Bluemke DA, Townsend RR, Vermeersch S, Segers P. Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis). J Am Coll Cardiol. 2012 Nov 20;60(21):2170-7. doi: 10.1016/j.jacc.2012.07.054. Epub 2012 Oct 24.
- Background: PubMed 20733089Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 1: pressure and flow measurements and basic principles of wave conduction and reflection. Hypertension. 2010 Oct;56(4):555-62. doi: 10.1161/HYPERTENSIONAHA.110.157321. Epub 2010 Aug 23.
- Background: PubMed 20733088Chirinos JA, Segers P. Noninvasive evaluation of left ventricular afterload: part 2: arterial pressure-flow and pressure-volume relations in humans. Hypertension. 2010 Oct;56(4):563-70. doi: 10.1161/HYPERTENSIONAHA.110.157339. Epub 2010 Aug 23.
- Background: PubMed 25533966Zamani P, Rawat D, Shiva-Kumar P, Geraci S, Bhuva R, Konda P, Doulias PT, Ischiropoulos H, Townsend RR, Margulies KB, Cappola TP, Poole DC, Chirinos JA. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation. 2015 Jan 27;131(4):371-80; discussion 380. doi: 10.1161/CIRCULATIONAHA.114.012957. Epub 2014 Dec 22.
- Background: PubMed 27927683Zamani P, Tan V, Soto-Calderon H, Beraun M, Brandimarto JA, Trieu L, Varakantam S, Doulias PT, Townsend RR, Chittams J, Margulies KB, Cappola TP, Poole DC, Ischiropoulos H, Chirinos JA. Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction. Circ Res. 2017 Mar 31;120(7):1151-1161. doi: 10.1161/CIRCRESAHA.116.309832. Epub 2016 Dec 7.
- Background: PubMed 30827125Muntner P, Shimbo D, Carey RM, Charleston JB, Gaillard T, Misra S, Myers MG, Ogedegbe G, Schwartz JE, Townsend RR, Urbina EM, Viera AJ, White WB, Wright JT Jr. Measurement of Blood Pressure in Humans: A Scientific Statement From the American Heart Association. Hypertension. 2019 May;73(5):e35-e66. doi: 10.1161/HYP.0000000000000087.
- Background: PubMed 20409919White WB, Krishnan S, Giacco S, Mallareddy M. Effects of metoprolol succinate extended release vs. amlodipine besylate on the blood pressure, heart rate, and the rate-pressure product in patients with hypertension. J Am Soc Hypertens. 2008 Sep-Oct;2(5):378-84. doi: 10.1016/j.jash.2008.03.002. Epub 2008 Jun 5.
- Derived from this study: PubMed 42137945Cohen JB, Hossain A, Chittams J, Zhao M, Afable J, Greenip A, Maynard H, Pourmussa B, Prenner SB, Selvaraj S, Townsend RR, Zamani P, Chirinos JA. Calcium Channel Blockade Versus beta-Blockade for Hypertension in Heart Failure With Preserved Ejection Fraction: A Randomized Crossover Trial. Hypertension. 2026 Jul;83(7):e26801. doi: 10.1161/HYPERTENSIONAHA.126.26801. Epub 2026 May 15.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 Amlodipine Besylate and Metoprolol Succinate in people with Heart Failure With Preserved Ejection Fraction and Hypertension, run by University of Pennsylvania 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 6 inclusion and 12 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: finished, as of the sponsor's last update on 30 Jan 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?
Yes. Results are posted in the registry (first posted 30 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Home Systolic Blood Pressure (time frame: Measured during the last week of each of the two 4-week intervention phases). 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 NCT04434664, which also lists 9 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 30 Jan 2026.