Diastolic Heart Failure, Heart Failure With Preserved Ejection Fraction, Pulmonary Hypertension
Conditions
Brief summary
Heart failure with preserved ejection fraction (HFpEF), is one of the leading causes of pulmonary hypertension (PH). Despite the severity of this disease, no established treatments exist for this class of PH. Nebivolol is a drug used in high blood pressure and heart failure, but not used in patients with PH. Due to some additional properties it possesses, the investigators believe nebivolol will improve disease severity in patients with PH associated with HFpEF. The hypothesis of this research study is that nebivolol improves PH severity in patients with HFpEF, as measured by hemodynamic and clinical parameters.
Detailed description
This research study will be a prospective, open-label 18-week clinical study of nebivolol in patients with PH associated with HFpEF. Patients will be identified in clinic based on echocardiogram (TTE) and right heart catheterization (RHC) results (both part of standard clinical care) indicating PH and HFpEF.
Interventions
DRUGNebivolol
Nebivolol will be started at 2.5 mg by mouth daily if on a beta-blocker the dose will start at 5mg, and titrated up to 10 mg daily, as tolerated.
Sponsors
National Institute of General Medical Sciences (NIGMS)
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (≥ 18 years of age) with World Health Organization Group 2 Pulmonary Hypertension (Mean pulmonary artery pressure ≥ 25 mmHg and pulmonary capillary wedge pressure ≥ 15 mmHg) * New York Heart Association class II-IV symptoms * Left ventricular ejection fraction (LVEF) ≥ 45%
Exclusion criteria
* Other causes of heart failure other than diastolic dysfunction, such as restrictive cardiomyopathy or infiltrative cardiomyopathy * Women who are pregnant or nursing * Liver cirrhosis, * Primary valvular disease * Acute coronary syndrome * Causes of PH other than that of heart failure, such as: chronic thromboembolic PH, sickle-cell disease, or sarcoidosis * Severe bradycardia or greater than 1st degree heart block * Decompensated heart failure * Current use of a third generation beta-blocker (nebivolol, carvedilol, or labetalol) or high dose of any beta-blockers (greater than 100 mg daily of metoprolol, or equivalent)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pulmonary Vascular Pressure | baseline - 18 weeks | Difference between baseline and 18 week mean pulmonary artery pressure and pulmonary artery wedge pressure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in 6-minute Walk Distance | baseline - 18 weeks | Difference in 6-minute walk distance between baseline and 18 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Participants will be started at 2.5 mg of nebivolol by mouth daily if on a beta-blocker the dose will start at 5mg, and titrated up to 10 mg daily, as tolerated.
Nebivolol: Nebivolol will be started at 2.5 mg by mouth daily if on a beta-blocker the dose will start at 5mg, and titrated up to 10 mg daily, as tolerated. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Nebivolol |
|---|---|
| Age, Continuous | 65.8 years STANDARD_DEVIATION 9.8 |
| Diastolic Blood Pressure | 68.0 mmHg STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 164.6 cm STANDARD_DEVIATION 9.4 |
| Mean Pulmonary Artery Pressure | 35.2 mmHg STANDARD_DEVIATION 7.2 |
| Pulmonary Artery Wedge Pressure | 19.6 mmHg STANDARD_DEVIATION 3.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 2 Participants |
| Systolic Blood Pressure | 130.1 mmHg STANDARD_DEVIATION 16 |
| Weight | 93.0 kilograms STANDARD_DEVIATION 29.8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 2 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Changes in Pulmonary Vascular Pressure
Difference between baseline and 18 week mean pulmonary artery pressure and pulmonary artery wedge pressure
Time frame: baseline - 18 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Changes in Pulmonary Vascular Pressure | Mean Pulmonary Artery Pressure Change | 0.43 mmHg | Standard Deviation 6.32 |
| Nebivolol | Changes in Pulmonary Vascular Pressure | Pulmonary Artery Wedge Pressure Change | 1.0 mmHg | Standard Deviation 7 |
Secondary
Changes in 6-minute Walk Distance
Difference in 6-minute walk distance between baseline and 18 weeks.
Time frame: baseline - 18 weeks
Population: Only patients who were able to complete walk tests at baseline and final study visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol | Changes in 6-minute Walk Distance | -44.0 feet | Standard Deviation 299.8 |