Improving Treatment Personalization of Pulmonary Hypertension Associated With Diastolic Heart Failure

• Sponsor: University of Florida (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02053246
• Collaborator: National Institute of General Medical Sciences (NIGMS) (NIH)
• Enrollment: 11
• Location: 1
• Arm: 1
• Actual Duration (Months): 85.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Hypertension; Diastolic Heart Failure; Heart Failure With Preserved Ejection Fraction	Drug: Nebivolol	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Improving Treatment Personalization of Pulmonary Hypertension Associated With Diastolic Heart Failure
• Actual Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: Mar 1, 2021
• Actual Study Completion Date: Mar 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. Changes in Pulmonary Vascular Pressure [baseline - 18 weeks]

   Difference between baseline and 18 week mean pulmonary artery pressure and pulmonary artery wedge pressure

Secondary Outcome Measures

1. Changes in 6-minute Walk Distance [baseline - 18 weeks]

   Difference in 6-minute walk distance between baseline and 18 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32611

Sponsors and Collaborators

• University of Florida
• National Institute of General Medical Sciences (NIGMS)

Investigators

• Principal Investigator: Julio Duarte, PharmD, PhD, University of Florida

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 8, 2018
• Informed Consent Form - Mar 6, 2019

More Information

Publications

None provided.

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT02053246
• Other Study ID Numbers: IRB201501144 -N; K23GM112014
• First Posted: Feb 3, 2014
• Last Update Posted: Feb 10, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hypertension, Pulmonary; Hypertension; Heart Failure; Heart Failure, Diastolic; Nebivolol

Study Results

Participant Flow

Arm/Group Title	Nebivolol
Arm/Group Description	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.
Period Title: Overall Study
STARTED	11
COMPLETED	7
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Nebivolol
Arm/Group Description	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.
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.8 (9.8)
Sex: Female, Male (Count of Participants)
Female	9 81.8%
Male	2 18.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%
Not Hispanic or Latino	10 90.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 36.4%
White	6 54.5%
More than one race	1 9.1%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	93.0 (29.8)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	164.6 (9.4)
Systolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	130.1 (16.0)
Diastolic Blood Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	68.0 (12.7)
Mean Pulmonary Artery Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	35.2 (7.2)
Pulmonary Artery Wedge Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	19.6 (3.7)

Outcome Measures

1. Primary Outcome

Title	Changes in Pulmonary Vascular Pressure
Description	Difference between baseline and 18 week mean pulmonary artery pressure and pulmonary artery wedge pressure
Time Frame	baseline - 18 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nebivolol
Arm/Group Description	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.
Measure Participants	7
Mean Pulmonary Artery Pressure Change	0.43 (6.32)
Pulmonary Artery Wedge Pressure Change	1.0 (7.0)

2. Secondary Outcome

Title	Changes in 6-minute Walk Distance
Description	Difference in 6-minute walk distance between baseline and 18 weeks.
Time Frame	baseline - 18 weeks

Outcome Measure Data

Analysis Population Description

Only patients who were able to complete walk tests at baseline and final study visits.

Arm/Group Title	Nebivolol
Arm/Group Description	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.
Measure Participants	4
Mean (Standard Deviation) [feet]	-44.0 (299.8)

Adverse Events

Time Frame	Data were collected from enrollment until completion of final study visit at week 18.
Arm/Group Title	Nebivolol
Arm/Group Description	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.
All Cause Mortality
	Nebivolol
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Serious Adverse Events
	Nebivolol
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	Nebivolol
	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)
General disorders
Dizziness	1/9 (11.1%)	1
Renal and urinary disorders
Fluid retention	1/9 (11.1%)	1

Limitations/Caveats

Trial was stopped prior to completion because funding ended.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.