Trial Outcomes & Findings for Safety Study to Lower the Risk of Heart Failure is Also Effective in Reducing Stiffness of the Arteries (NCT NCT00829296)

Results Overview

Changes in aortic impedance in patients on nebivolol vs. metoprolol succinate in Type 2 hypertensive diabetic patients as measured by the change from baseline in central systolic blood pressure.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

70 participants

Primary outcome timeframe

Baseline and 26 Weeks

Results posted on

2016-02-05

Participant Flow

Participant milestones

Participant milestones
Measure	Nebivolol Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Overall Study STARTED	34	36
Overall Study COMPLETED	29	32
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Nebivolol Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Overall Study Adverse Event	5	4

Baseline Characteristics

Safety Study to Lower the Risk of Heart Failure is Also Effective in Reducing Stiffness of the Arteries

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nebivolol n=34 Participants Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol n=36 Participants Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol	Total n=70 Participants Total of all reporting groups
Age, Continuous	65.0 years STANDARD_DEVIATION 6.9 • n=5 Participants	64.1 years STANDARD_DEVIATION 6.1 • n=7 Participants	64.5 years STANDARD_DEVIATION 6.4 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	27 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 26 Weeks

Population: Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

Changes in aortic impedance in patients on nebivolol vs. metoprolol succinate in Type 2 hypertensive diabetic patients as measured by the change from baseline in central systolic blood pressure.

Outcome measures

Outcome measures
Measure	Nebivolol n=29 Participants Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol n=32 Participants Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Change in Central Systolic Blood Pressure (SBP) Aortic Systolic Blood Pressure at Baseline	125.3 mmHg Standard Deviation 8.0	127.8 mmHg Standard Deviation 8.8
Change in Central Systolic Blood Pressure (SBP) Aortic Systolic Blood Pressure at 26 Weeks	121.6 mmHg Standard Deviation 8.2	123.8 mmHg Standard Deviation 11.1

SECONDARY outcome

Timeframe: Baseline and 26 Weeks

Population: Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse wave velocity.

Outcome measures

Outcome measures
Measure	Nebivolol n=29 Participants Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol n=32 Participants Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Change in Pulse Wave Velocity (PWV) Pulse wave velocity at Baseline	6.48 m/s Standard Deviation 0.8	6.52 m/s Standard Deviation 1.2
Change in Pulse Wave Velocity (PWV) Pulse wave velocity at 26 Weeks	6.3 m/s Standard Deviation 0.9	6.4 m/s Standard Deviation 1.3

SECONDARY outcome

Timeframe: Baseline and 26 Weeks

Population: Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

Augmentation index is defined as the percentage of the central pulse pressure which is attributed to the reflected pulse wave and, therefore, reflects the degree to which central arterial pressure is augmented by wave reflection.

Outcome measures

Outcome measures
Measure	Nebivolol n=29 Participants Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol n=32 Participants Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Change in Augmentation Index Augmentation index at Baseline	22.0 percent (%) Standard Deviation 7.1	26.2 percent (%) Standard Deviation 8.3
Change in Augmentation Index Augmentation index at 26 Weeks	22.1 percent (%) Standard Deviation 7.4	24.6 percent (%) Standard Deviation 6.7

SECONDARY outcome

Timeframe: Baseline and 26 Weeks

Population: Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse pressure amplification (central pulse pressure /brachial pulse pressure).

Outcome measures

Outcome measures
Measure	Nebivolol n=29 Participants Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol n=32 Participants Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Change in Pulse Pressure Amplification Pulse pressure amplification at Baseline	0.77 ratio Standard Deviation 0.08	0.79 ratio Standard Deviation 0.09
Change in Pulse Pressure Amplification Pulse pressure amplification at 26 Weeks	0.83 ratio Standard Deviation 0.09	0.85 ratio Standard Deviation 0.12

Adverse Events

Nebivolol

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Metoprolol

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Nebivolol n=34 participants at risk Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Metoprolol n=36 participants at risk Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
General disorders Fatigue	5.9% 2/34	16.7% 6/36
Gastrointestinal disorders Diarrhea	11.8% 4/34	5.6% 2/36
Nervous system disorders Dizziness	5.9% 2/34	2.8% 1/36

Additional Information

Dr. George Bakris

University of Chicago

Phone: 773-702-7936

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place