<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04434664</url>
  </required_header>
  <id_info>
    <org_study_id>833517</org_study_id>
    <nct_id>NCT04434664</nct_id>
  </id_info>
  <brief_title>BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in HFpEF</brief_title>
  <acronym>BLOCK HFpEF</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Julio Chirinos, MD, PhD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Raymond Townsend, MD</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Heart failure with preserved ejection fraction (HFpEF) is a critical public health problem.&#xD;
      Heart failure (HF) affects over 5 million adults in the United States (US), and is a major&#xD;
      source of morbidity, mortality, and impaired quality of life. Approximately half of&#xD;
      individuals with HF have a preserved left ventricular (LV) ejection fraction (EF), termed HF&#xD;
      with preserved EF (HFpEF). While there are several effective pharmacologic therapies for HF&#xD;
      with reduced ejection fraction (HFrEF), none have been identified for HFpEF. Hypertension,&#xD;
      which is present in approximately 80% of individuals with HFpEF, is the foremost modifiable&#xD;
      risk factor for the development and progression of HFpEF. Despite the clinical importance of&#xD;
      hypertension in HFpEF, there is limited information on how common antihypertensive agents,&#xD;
      particularly calcium channel blockers (CCBs) and β-blockers, effect pathophysiologic&#xD;
      mechanisms of HFpEF. This is a mechanistic investigation of the role of dihydropyridine CCBs&#xD;
      compared to β-blockers (commonly used antihypertensive agents in clinical practice) in&#xD;
      targeting key physiologic abnormalities in HFpEF.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2021</start_date>
  <completion_date type="Anticipated">October 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>For blinding, tablets are placed into oral gelatin capsules with an inert filler (lactose monohydrate). Blinding is performed and maintained by the University of Pennsylvania Investigational Drug Service.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in home systolic blood pressure</measure>
    <time_frame>Measured during the last week of each of the two 4-week intervention phases</time_frame>
    <description>Mean systolic BP measured using home BP monitoring (Microlife BP 3MX1-4 WatchBP Home N)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in home diastolic blood pressure</measure>
    <time_frame>Measured during the last week of each of the two 4-week intervention phases</time_frame>
    <description>Mean systolic BP measured using home BP monitoring (Microlife BP 3MX1-4 WatchBP Home N).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in office systolic and diastolic blood pressure</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>Blood pressure will be measured at rest with a validated oscillometric device (Omron 705IT; HEM-759-E).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peak oxygen consumption (VO2) during a maximal exercise test</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systemic vasodilatory response to exercise</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>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 reduction in SVR during exercise, relative to SVR at rest ([rest SVR - peak exercise SVR] / rest SVR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in arterial wave reflections</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>We will use a high-fidelity Millar applanation tonometer to record carotid pressure waveforms, which will be calibrated using brachial diastolic and mean pressures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in large artery stiffness</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>We will use a tonometer to record large artery stiffness determined by carotid-femoral pulse wave velocity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in left ventricular filling pressure</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>We will assess the ratio of early diastolic mitral inflow velocity to mitral annular tissue velocity (a surrogate of LV filling pressures) on echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in myocardial strain</measure>
    <time_frame>Measured at the end of each of the two 4-week intervention phases</time_frame>
    <description>Systolic function will be assessed via systolic myocardial strain using speckle tracking echocardiography</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Heart Failure With Preserved Ejection Fraction</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Amlodipine besylate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metoprolol succinate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amlodipine Besylate</intervention_name>
    <description>The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period</description>
    <arm_group_label>Amlodipine besylate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metoprolol Succinate</intervention_name>
    <description>The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period</description>
    <arm_group_label>Metoprolol succinate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adults age 18-90 years&#xD;
&#xD;
          2. Diagnosis of hypertension defined by at least two of the following: A) ICD-9&#xD;
             (401.0-404.91) or ICD-10 (I10-I13) codes signifying hypertension; B) Treatment with&#xD;
             antihypertensive medication other than a loop diuretic for at least two months; C)&#xD;
             History of previous blood pressure readings ≥130/80 mmHg at two separate office visits&#xD;
&#xD;
          3. Stable antihypertensive therapy; defined as no changes in antihypertensive medications&#xD;
             in the preceding 30 days&#xD;
&#xD;
          4. A diagnosis of heart failure&#xD;
&#xD;
          5. LV ejection fraction &gt;50%&#xD;
&#xD;
          6. Elevated filling pressures defined by at least one of the following criteria: A)&#xD;
             Mitral E/e' ratio (lateral or septal) &gt;8 with low e' velocity (septal e' &lt;7 cm/s or&#xD;
             lateral e' &lt;10 cm/s) and at least one of the following: a. Enlarged left atrium (LA&#xD;
             volume index &gt;34 ml/m2); b. Chronic loop diuretic use for management of symptoms; c.&#xD;
             Elevated natriuretic peptides (BNP levels &gt;100 ng/L or NT-proBNP levels &gt;300 ng/L); B)&#xD;
             Mitral E/e' ratio (lateral or septal) &gt;14; C) Previously elevated invasively&#xD;
             determined filling pressures based on one of the following criteria: a. Resting LVEDP&#xD;
             &gt;16 mmHg; b. Mean PCWP &gt;12 mmHg; c. PCWP or LVEDP ≥25 mmHg with exercise; D) Previous&#xD;
             acutely decompensated heart failure requiring IV diuretics;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Systolic BP meeting any of the following criteria: A) Current office systolic BP &lt;100&#xD;
             mmHg; B) Current office systolic BP 100-119 mmHg if not receiving treatment with an&#xD;
             antihypertensive agent or if holding antihypertensive medication prior to&#xD;
             randomization would be clinically contraindicated, as per the investigator's clinical&#xD;
             judgement; C) Current office systolic BP ≥180 mmHg if not receiving treatment with a&#xD;
             CCB or β-blocker, or ≥160 mmHg if already receiving a CCB and/or β-blocker prior to&#xD;
             the pre-randomization wash-out period; D) Orthostatic hypotension defined as &gt;20 mmHg&#xD;
             decline in office systolic BP 3-5 minutes following the transition from sitting to&#xD;
             standing position&#xD;
&#xD;
          2. Resting heart rate &lt;50 or &gt;100 bpm&#xD;
&#xD;
          3. Contraindication to withholding CCB or β-blocker therapy (e.g. use of&#xD;
             non-dihydropyridine CCB [diltiazem or verapamil] or β-blocker for rate control for&#xD;
             atrial fibrillation) as per the investigator's clinical judgement&#xD;
&#xD;
          4. Children, fetuses, neonates, prisoners, and pregnant women (women of childbearing age&#xD;
             will undergo a pregnancy test during the screening visit) are not included in this&#xD;
             research study.&#xD;
&#xD;
          5. Inability/unwillingness to exercise&#xD;
&#xD;
          6. Any the following echocardiographic findings: A) LV ejection fraction &lt;45% on any&#xD;
             prior echocardiogram, unless it was in the setting of uncontrolled atrial&#xD;
             fibrillation; B) Hypertrophic, infiltrative, or inflammatory cardiomyopathy; C)&#xD;
             Clinically significant pericardial disease, as per investigator judgment; D) Moderate&#xD;
             or greater left-sided valvular disease, any degree of mitral stenosis, or prosthetic&#xD;
             mitral valve; E) Severe right-sided valvular disease; F) Severe right ventricular&#xD;
             dysfunction&#xD;
&#xD;
          7. Active coronary artery disease, defined as any of the following: A) Acute coronary&#xD;
             syndrome or coronary intervention in the past 2 months; B) Ischemia on stress testing&#xD;
             without either subsequent revascularization or a subsequent angiogram demonstrating&#xD;
             the absence of clinically significant epicardial coronary artery disease, as per&#xD;
             investigator judgement&#xD;
&#xD;
          8. Clinically significant lung disease, defined as any of the following: A) Chronic&#xD;
             Obstructive Pulmonary Disease meeting GOLD criteria stage III or greater; B) Treatment&#xD;
             with oral steroids within the past 6 months for an exacerbation of obstructive lung&#xD;
             disease; C) The use of daytime supplemental oxygen&#xD;
&#xD;
          9. Primary pulmonary arteriopathy&#xD;
&#xD;
         10. eGFR &lt;30 mL/min/1.73m2&#xD;
&#xD;
         11. Any medical condition that, under the investigator's discretion, will interfere with&#xD;
             safe completion of the study or validity of the endpoint assessments&#xD;
&#xD;
         12. Known history of an allergy or clinically significant sensitivity (as determined by&#xD;
             the investigator) to either amlodipine besylate or metoprolol succinate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jordana Cohen, MD, MSCE</last_name>
    <phone>267-588-7914</phone>
    <email>jco@pennmedicine.upenn.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jordana Cohen, MD, MSCE</last_name>
    </contact>
    <investigator>
      <last_name>Julio Chirinos, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Raymond Townsend, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jesse Chittams, MS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>31926856</PMID>
  </reference>
  <reference>
    <citation>Chirinos 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.</citation>
    <PMID>23103044</PMID>
  </reference>
  <reference>
    <citation>Chirinos 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.</citation>
    <PMID>20733089</PMID>
  </reference>
  <reference>
    <citation>Chirinos 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.</citation>
    <PMID>20733088</PMID>
  </reference>
  <reference>
    <citation>Zamani 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.</citation>
    <PMID>25533966</PMID>
  </reference>
  <reference>
    <citation>Zamani 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.</citation>
    <PMID>27927683</PMID>
  </reference>
  <reference>
    <citation>Muntner 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.</citation>
    <PMID>30827125</PMID>
  </reference>
  <reference>
    <citation>White 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.</citation>
    <PMID>20409919</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pennsylvania</investigator_affiliation>
    <investigator_full_name>Jordana Cohen, MD, MSCE</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine and Epidemiology</investigator_title>
  </responsible_party>
  <keyword>Calcium channel blocker</keyword>
  <keyword>Beta-blocker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metoprolol</mesh_term>
    <mesh_term>Amlodipine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04434664
org study id: 833517
nct id: NCT04434664
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: For blinding, tablets are placed into oral gelatin capsules with an inert filler (lactose monohydrate). Blinding is performed and maintained by the University of Pennsylvania Investigational Drug Service.
measure: Change in home systolic blood pressure
time frame: Measured during the last week of each of the two 4-week intervention phases
description: Mean systolic BP measured using home BP monitoring (Microlife BP 3MX1-4 WatchBP Home N)
measure: Change in home diastolic blood pressure
time frame: Measured during the last week of each of the two 4-week intervention phases
description: Mean systolic BP measured using home BP monitoring (Microlife BP 3MX1-4 WatchBP Home N).
measure: Change in office systolic and diastolic blood pressure
time frame: Measured at the end of each of the two 4-week intervention phases
description: Blood pressure will be measured at rest with a validated oscillometric device (Omron 705IT; HEM-759-E).
measure: Change 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
description: 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.
measure: Change in quality of life
time frame: Measured at the end of each of the two 4-week intervention phases
description: 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.
measure: Change in systemic vasodilatory response to exercise
time frame: Measured at the end of each of the two 4-week intervention phases
description: 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 reduction in SVR during exercise, relative to SVR at rest ([rest SVR - peak exercise SVR] / rest SVR).
measure: Change in arterial wave reflections
time frame: Measured at the end of each of the two 4-week intervention phases
description: We will use a high-fidelity Millar applanation tonometer to record carotid pressure waveforms, which will be calibrated using brachial diastolic and mean pressures.
measure: Change in large artery stiffness
time frame: Measured at the end of each of the two 4-week intervention phases
description: We will use a tonometer to record large artery stiffness determined by carotid-femoral pulse wave velocity.
measure: Change in left ventricular filling pressure
time frame: Measured at the end of each of the two 4-week intervention phases
description: We will assess the ratio of early diastolic mitral inflow velocity to mitral annular tissue velocity (a surrogate of LV filling pressures) on echocardiography
measure: Change in myocardial strain
time frame: Measured at the end of each of the two 4-week intervention phases
description: Systolic function will be assessed via systolic myocardial strain using speckle tracking echocardiography
arm group label: Amlodipine besylate
arm group type: Active Comparator
description: 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
arm group label: Metoprolol succinate
arm group type: Active Comparator
description: 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
intervention type: Drug
intervention name: Amlodipine Besylate
description: The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period
arm group label: Amlodipine besylate
intervention type: Drug
intervention name: Metoprolol Succinate
description: The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period
arm group label: Metoprolol succinate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Jordana Cohen, MD, MSCE
phone: 267-588-7914
email: jco@pennmedicine.upenn.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United States
citation: 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.
PMID: 31926856
citation: Chirinos 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.
PMID: 23103044
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responsible party type: Principal Investigator
investigator affiliation: University of Pennsylvania
investigator full name: Jordana Cohen, MD, MSCE
investigator title: Assistant Professor of Medicine and Epidemiology
mesh term: Hypertension
mesh term: Heart Failure
mesh term: Metoprolol
mesh term: Amlodipine