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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amlodipine Besylate | Drug | The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 during the last week of each of the two 4-week intervention phases |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31926856 | Background | 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. | |
| 23103044 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Amlodipine Besylate, Then Metoprolol Succinate | Drug: Amlodipine besylate, 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. Drug: Metoprolol succinate. 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 |
| FG001 | Metoprolol Succinate, Then Amlodipine Besylate | Drug: Metoprolol succinate, 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. Drug: Amlodipine besylate, 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (4 weeks) |
| |||||||||||||
| Washout (one week) |
| |||||||||||||
| Second Intervention (4 weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Amlodipine Besylate, Then Metoprolol Succinate | Drug: Amlodipine besylate, 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. Drug: Metoprolol succinate. 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | mm Hg | Measured during the last week of each of the two 4-week intervention phases |
|
From enrollment until the end of follow-up, an average of 10 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amlodipine Besylate | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Cardiac disorders | Non-systematic Assessment | Assessed by PI. Grade 3, unrelated, unexpected |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | Non-systematic Assessment | Grade 1, expected |
Sample size; while the study was adequately powered for the primary outcome, the small sample size yielded imbalance in some baseline characteristics and limits the ability to draw conclusions from the secondary outcomes.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jordana Cohen, MD, MSCE | University of Pennsylvania | 215-573-6074 | jco@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 2, 2024 | Nov 14, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 27, 2025 | Nov 14, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017311 | Amlodipine |
| D008790 | Metoprolol |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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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.
| Metoprolol Succinate | Drug | The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period |
|
| 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 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 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 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 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 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 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 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 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 at the end of each of the two 4-week intervention phases |
| Background |
| 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. |
| 20733089 | Background | 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. |
| 20733088 | Background | 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. |
| 25533966 | Background | 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. |
| 27927683 | Background | 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. |
| 30827125 | Background | 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. |
| 20409919 | Background | 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. |
| 42137945 | Derived | Cohen 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. |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Metoprolol Succinate, Then Amlodipine Besylate | Drug: Metoprolol succinate, 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. Drug: Amlodipine besylate, 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Office Systolic Blood Pressure | Determined using the average of three seated, successive, automated blood pressure readings using guideline-recommended approach, performed by a trained member of the study team. | Mean | Standard Deviation | mm Hg |
|
| Office Diastolic Blood Pressure | Determined using the average of three seated, successive, automated blood pressure readings using guideline-recommended approach, performed by a trained member of the study team. | Mean | Standard Deviation | mm Hg |
|
| New York Heart Association Class | Study clinician-determined severity of heart failure symptoms. Class I indicates no physical limitations. Class II indicates slight limitation in physical activity. Class III indicates more significant limitations in physical activity. Class IV indicates severe limitations in physical activity with symptoms event present at rest. | Count of Participants | Participants |
|
| N-terminal Pro-B-type Natriuretic Peptide | Blood test determined using plasma collection | Median | Inter-Quartile Range | pg/mL |
|
| Septal E/e' | Calculated as the ratio of early diastolic mitral inflow velocity (E) in cm/s to septal mitral annular tissue velocity (e'; a surrogate of left ventricular filling pressures) in cm/s determined on echocardiography | Mean | Standard Deviation | ratio |
|
| Kansas City Cardiomyopathy Questionnaire | 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. | Mean | Standard Deviation | score |
|
| OG001 |
| Metoprolol Succinate |
Metoprolol succinate. 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. |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | mm Hg | Measured during the last week of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | Difference in Office Systolic Blood Pressure | Blood pressure will be measured at rest with a validated oscillometric device (Uscom BP+/UM-211). | Two individuals did not complete their final study visit/did not provide sufficient data to calculate the final estimate | Posted | Mean | Standard Deviation | mm Hg | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | Difference in Office Diastolic Blood Pressure | Blood pressure will be measured at rest with a validated oscillometric device (Uscom BP+/UM-211). | Two individuals did not complete their final study visit/did not provide sufficient data to calculate the final estimate | Posted | Mean | Standard Deviation | mm Hg | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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. | Eight individuals did not complete exercise testing during at least one of their endpoint visits | Posted | Mean | Standard Deviation | ml/min/kg | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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. | One individual was unable to complete the questionnaire at one of their endpoint visits | Posted | Mean | Standard Deviation | score on a scale | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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%. | Ten individuals did not complete the necessary exercise testing and/or echocardiography during at least one endpoint visit | Posted | Mean | Standard Deviation | Percentage reduction | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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. | 6 individuals did not have the necessary tonometry readings captured during at least one endpoint visit | Posted | Mean | Standard Deviation | ratio of backward to forward waveforms | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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. | Six individuals did not complete the necessary tonometry measurements during at least one endpoint visit | Posted | Mean | Standard Deviation | m/s | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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 | Three individuals did not complete the necessary echocardiographic measurements during at least one endpoint visit | Posted | Mean | Standard Deviation | ratio of E/e' | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| Secondary | 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. | Twelve individuals did not have the necessary echocardiographic measurements performed during at least one study visit | Posted | Mean | Standard Deviation | Percentage change in length | Measured at the end of each of the two 4-week intervention phases |
|
|
|
|
| 0 |
| 45 |
| 1 |
| 45 |
| 33 |
| 45 |
| EG001 | Metoprolol Succinate | 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 | 0 | 46 | 0 | 46 | 36 | 46 |
|
| Arrhythmia | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Low blood pressure | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| High blood pressure | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Worsening heart failure | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Worsening kidney function | Renal and urinary disorders | Systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Rising liver enzymes | Hepatobiliary disorders | Systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Chest pain | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, unexpected |
|
| Loose stools | Gastrointestinal disorders | Non-systematic Assessment | Assessed by PI, Grade 1, unexpected |
|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Fatigue at rest | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Leg swelling | Cardiac disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Lightheadedness | Nervous system disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Assessed by PI, Grade 1, expected |
|
| Cramping or pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Assessed by PI, Grade 1, unexpected, unrelated |
|
| Headache | Nervous system disorders | Non-systematic Assessment | Assessed by PI, Grade 1, unexpected, unrelated |
|
| Abnormal serum calcium | Renal and urinary disorders | Non-systematic Assessment | Assessed by PI, Grade 1, unexpected, unrelated |
|
| Hypoxia (spO2 90-94%) or dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Assessed by PI, Grade 1, unexpected, unrelated |
|
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| D050198 |
| Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |