Trial Outcomes & Findings for Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells (NCT NCT01041287)

NCT ID: NCT01041287

Last Updated: 2014-12-19

Results Overview

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 96 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2014-12-19

Participant Flow

Patients recruited from clinic sites at Emory University Hospital and by advertisements between December 2009 through April 2012.

There were 96 subjects enrolled. 58 of the subjects were withdrawn prior to group assignment. 39 subjects did not meet eligibility criteria and 19 subjects withdrew.

Participant milestones

Measure	Nebivolol/ Metoprolol Subjects were randomized to nebivolol for the first 3 months. Then they "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol Subjects were randomized to metoprolol succinate for the first 3 months. Then they "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.
Treatment Period 1 (3 Months) STARTED	19	19
Treatment Period 1 (3 Months) COMPLETED	19	19
Treatment Period 1 (3 Months) NOT COMPLETED	0	0
Treatment Period 2 (3 Months) STARTED	19	19
Treatment Period 2 (3 Months) COMPLETED	16	14
Treatment Period 2 (3 Months) NOT COMPLETED	3	5

Reasons for withdrawal

Measure	Nebivolol/ Metoprolol Subjects were randomized to nebivolol for the first 3 months. Then they "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol Subjects were randomized to metoprolol succinate for the first 3 months. Then they "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.
Treatment Period 2 (3 Months) Lost to Follow-up	3	3
Treatment Period 2 (3 Months) Adverse Event	0	2

Baseline Characteristics

Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells

Baseline characteristics by cohort

Measure	Nebivolol/ Metoprolol n=16 Participants Subjects were randomized to nebivolol for 3 months. They "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol n=14 Participants Subjects were randomized to metoprolol succinate for 3 months. They "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).

Outcome measures

Measure	Nebivolol/ Metoprolol n=16 Participants Subjects were randomized to nebivolol for the first 3 months. Then they "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol n=14 Participants Subjects were randomized to metoprolol succinate for the first 3 months. Then they "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.
Pulse Wave Velocity (Measure of Arterial Stiffness)	9.4 meters per second (m/s) Standard Deviation 2.6	8.9 meters per second (m/s) Standard Deviation 1.5

PRIMARY outcome

Timeframe: 3 months

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).

Outcome measures

Measure	Nebivolol/ Metoprolol n=16 Participants Subjects were randomized to nebivolol for the first 3 months. Then they "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol n=14 Participants Subjects were randomized to metoprolol succinate for the first 3 months. Then they "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.
Pulse Wave Velocity (Measure of Arterial Stiffness)	8.4 meters per second (m/s) Standard Deviation 2.4	10.1 meters per second (m/s) Standard Deviation 1.4

PRIMARY outcome

Timeframe: 6 months

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s).

Outcome measures

Measure	Nebivolol/ Metoprolol n=16 Participants Subjects were randomized to nebivolol for the first 3 months. Then they "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol n=16 Participants Subjects were randomized to metoprolol succinate for the first 3 months. Then they "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.
Pulse Wave Velocity (Measure of Arterial Stiffness)	9.1 meters per second (m/s) Standard Deviation 2.2	9.8 meters per second (m/s) Standard Deviation 1.6

Adverse Events

Nebivolol/ Metoprolol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Metoprolol/Nebivolol

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nebivolol/ Metoprolol n=19 participants at risk Subjects were randomized to nebivolol for the first 3 months. Then they "crossed over" to take 3 months of metoprolol succinate. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.	Metoprolol/Nebivolol n=19 participants at risk Subjects were randomized to metoprolol succinate for the first 3 months. Then they "crossed over" to take 3 months of nebivolol. The initial 5 mg daily dose of nebivolol was titrated to 10 mg daily after 2 weeks if their BP remained \>125/80, and subsequently titrated to 20 mg daily after another 2 weeks if the BP remained \>125/80. Similarly, the initial 50 mg daily dose of metoprolol succinate was titrated to 100 mg daily after 2 weeks if BP remained \>125/80, and further increased to 200 mg after 2 weeks if BP remained \>125/80.
Cardiac disorders Stroke	0.00% 0/19 58 subjects were withdrawn prior to randomization/group assignment (no intervention occurred), therefore they are not accounted for in the at-risk population for the adverse events.	10.5% 2/19 58 subjects were withdrawn prior to randomization/group assignment (no intervention occurred), therefore they are not accounted for in the at-risk population for the adverse events.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Arshed Quyyumi

Emory University

Phone: 404-727-3655

Email: aquyyum@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place