Diabetes, Hypertension
Conditions
Keywords
diabetes, hypertension, aortic impedance
Brief summary
The study is being done to see if a drug shown to lower the risk of heart failure is also effective in reducing the stiffness of the arteries.
Detailed description
To determine the effect of nebivolol versus metoprolol in Type 2 hypertensive diabetic patients on systolic blood pressure and diastolic blood pressure.
Interventions
DRUGnebivolol
Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached
DRUGMetoprolol
Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached
Sponsors
Forest Laboratories
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Established Type 2 diabetic not treated with insulin * Stage 1 hypertensives blood pressure \> 130/80 mmHg and \< 160/100 mmHg * BMI \< 35 * Hemoglobin A1C \< 8.5 * Must be postmenopausal or taking some form of birth control of surgically sterile
Exclusion criteria
* Acute myocardial infarction, unstable angina, stroke or TIA within the past year. * Active angina in the last three months * Diabetes requiring treatment with insulin * Severe asthma * Female who are pregnant, planning to be pregnant during the study period, lactating or women of childbearing potential who are not using a medically approved method of contraception * Recent history of substance or alcohol abuse . * Uncontrolled hypertension systolic blood pressure \>160mmHg or diastolic blood pressure \> 100 mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Central Systolic Blood Pressure (SBP) | Baseline and 26 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulse Wave Velocity (PWV) | Baseline and 26 Weeks | 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. |
| Change in Augmentation Index | Baseline and 26 Weeks | 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. |
| Change in Pulse Pressure Amplification | Baseline and 26 Weeks | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached
nebivolol | 34 |
| Metoprolol Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached
Metoprolol | 36 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
Baseline characteristics
| Characteristic | Nebivolol | Metoprolol | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 6.9 | 64.1 years STANDARD_DEVIATION 6.1 | 64.5 years STANDARD_DEVIATION 6.4 |
| Sex: Female, Male Female | 23 Participants | 27 Participants | 50 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 34 | 9 / 36 |
| serious Total, serious adverse events | 0 / 34 | 0 / 36 |
Outcome results
Primary
Change in Central Systolic Blood Pressure (SBP)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Change in Central Systolic Blood Pressure (SBP) | Aortic Systolic Blood Pressure at Baseline | 125.3 mmHg | Standard Deviation 8 |
| Nebivolol | Change in Central Systolic Blood Pressure (SBP) | Aortic Systolic Blood Pressure at 26 Weeks | 121.6 mmHg | Standard Deviation 8.2 |
| Metoprolol | Change in Central Systolic Blood Pressure (SBP) | Aortic Systolic Blood Pressure at Baseline | 127.8 mmHg | Standard Deviation 8.8 |
| Metoprolol | Change in Central Systolic Blood Pressure (SBP) | Aortic Systolic Blood Pressure at 26 Weeks | 123.8 mmHg | Standard Deviation 11.1 |
Secondary
Change in Augmentation Index
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Change in Augmentation Index | Augmentation index at Baseline | 22.0 percent (%) | Standard Deviation 7.1 |
| Nebivolol | Change in Augmentation Index | Augmentation index at 26 Weeks | 22.1 percent (%) | Standard Deviation 7.4 |
| Metoprolol | Change in Augmentation Index | Augmentation index at Baseline | 26.2 percent (%) | Standard Deviation 8.3 |
| Metoprolol | Change in Augmentation Index | Augmentation index at 26 Weeks | 24.6 percent (%) | Standard Deviation 6.7 |
Secondary
Change in Pulse Pressure Amplification
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Change in Pulse Pressure Amplification | Pulse pressure amplification at Baseline | 0.77 ratio | Standard Deviation 0.08 |
| Nebivolol | Change in Pulse Pressure Amplification | Pulse pressure amplification at 26 Weeks | 0.83 ratio | Standard Deviation 0.09 |
| Metoprolol | Change in Pulse Pressure Amplification | Pulse pressure amplification at Baseline | 0.79 ratio | Standard Deviation 0.09 |
| Metoprolol | Change in Pulse Pressure Amplification | Pulse pressure amplification at 26 Weeks | 0.85 ratio | Standard Deviation 0.12 |
Secondary
Change in Pulse Wave Velocity (PWV)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nebivolol | Change in Pulse Wave Velocity (PWV) | Pulse wave velocity at 26 Weeks | 6.3 m/s | Standard Deviation 0.9 |
| Nebivolol | Change in Pulse Wave Velocity (PWV) | Pulse wave velocity at Baseline | 6.48 m/s | Standard Deviation 0.8 |
| Metoprolol | Change in Pulse Wave Velocity (PWV) | Pulse wave velocity at Baseline | 6.52 m/s | Standard Deviation 1.2 |
| Metoprolol | Change in Pulse Wave Velocity (PWV) | Pulse wave velocity at 26 Weeks | 6.4 m/s | Standard Deviation 1.3 |