BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in HFpEF

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2024-12-20

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Reduced Contractile Reserve: a Therapeutic Target in Heart Failure With Preserved Ejection Fraction(HFpEF)

NCT01354613

Heart Failure With Preserved Ejection Fraction Pulmonary Disease Left Ventricular Hypertrophy/Hypertension

COMPLETED NA

Enoximone Plus Extended-Release Metoprolol Succinate in Subjects With Advanced Chronic Heart Failure

NCT00077948

Heart Failure, Congestive

TERMINATED PHASE3

Matching Perfusion and Metabolic Activity in HFpEF

NCT04913805

Heart Failure With Preserved Ejection Fraction

RECRUITING PHASE2

A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction

NCT05139615

Acute Heart Failure With Reduced Ejection Fraction

TERMINATED PHASE2

Deprescribing Beta-Blockers in Elders With Heart Failure With Preserved Ejection Fraction (DEPRESCRIBE-HFpEF)

NCT07298993

Heart Failure HFpEF HFpEF - Heart Failure With Preserved Ejection Fraction

NOT_YET_RECRUITING PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Heart Failure with Preserved Ejection Fraction Hypertension

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type ACTIVE_COMPARATOR

Amlodipine Besylate

Intervention Type DRUG

The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period

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

Group Type ACTIVE_COMPARATOR

Metoprolol Succinate

Intervention Type DRUG

The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Amlodipine Besylate

The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period

Intervention Type DRUG

Metoprolol Succinate

The interventions will be implemented in random order in a crossover (AB-BA) design, separated by an approximately one-week washout period

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Adults age 18-90 years
2. 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
3. Stable antihypertensive therapy; defined as no changes in antihypertensive medications in the preceding 30 days
4. A diagnosis of heart failure
5. LV ejection fraction \>50%
6. 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;

Exclusion Criteria

1. 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
2. Resting heart rate \<50 or \>100 bpm
3. 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
4. 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.
5. Inability/unwillingness to exercise
6. 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
7. 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
8. 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
9. Primary pulmonary arteriopathy
10. eGFR \<30 mL/min/1.73m2
11. Any medical condition that, under the investigator's discretion, will interfere with safe completion of the study or validity of the endpoint assessments
12. Known history of an allergy or clinically significant sensitivity (as determined by the investigator) to either amlodipine besylate or metoprolol succinate

Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No