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| Name | Class |
|---|---|
| Forest Laboratories | INDUSTRY |
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High blood pressure (hypertension) is called the "silent killer" because many people do not know they have it, and do not know when it is well controlled. Unfortunately, over time uncontrolled hypertension can cause irreversible organ damage that can lead to heart attack, stroke, heart failure, and kidney failure. If a person cannot control their blood pressure with diet and exercise, doctors often prescribe medications to help control the blood pressure. Nebivolol is a medication that has been recently approved by the FDA for the treatment of hypertension. Our study will investigate whether treatment with nebivolol, as compared to another medication called metoprolol, in African Americans with hypertension will be more effective in protecting blood vessels against the harmful effects of high blood pressure.
Over time high blood pressure causes hardening of the arteries (atherosclerosis) which leads to narrowing of the blood vessels and reduces blood flow to our organs. Arteries also relax and contract naturally, which further changes the blood supply. When arteries are narrowed, exercise can bring on a condition in which the blood supply is inadequate, and this might result in the sensation of pain.
Cells lining our blood vessels produce a variety of substances that normally cause arteries to relax. Two of these substances are called nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). We are trying to determine the nature of these substances in African Americans with high blood pressure and how it is affected by nebivolol and metoprolol. One way to determine this is to inject drugs such as L-NMMA (N(G)-monomethyl-L-arginine) or TEA (tetraethylammonium chloride), which block the production of NO and EDHF respectively, and then study what happens to the blood flow at rest and during exercise. It is our thought that nebivolol, in comparison to metoprolol, will increase the substances that naturally cause arteries to relax and improve blood supply.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nebivolol followed by Metoprolol XL | Active Comparator | Subjects are randomized to Nebivolol 5mg and titrate to Nebivolol 10mg two weeks after drug initiation. Ten weeks after titration subjects will cross over to Metoprolol XL 50mg and titrate to Metoprolol XL 100mg two weeks after cross over. |
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| Metoprolol XL followed by Nebivolol | Active Comparator | Subjects are randomized to Metoprolol XL 50mg and titrate to Metoprolol XL 100mg two weeks after drug initiation. Ten weeks after titration subjects will cross over to Nebivolol 5mg and titrate to Nebivolol 10mg two weeks after cross over. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nebivolol | Drug | Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug. |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial Function Measured by Forearm Blood Flow (FBF) at 12 Weeks | Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute. | 12 weeks |
| Endothelial Function Measured by Forearm Blood Flow (FBF) at 24 Weeks | Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute. | 24 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26285691 | Result | Neuman RB, Hayek SS, Poole JC, Rahman A, Menon V, Kavtaradze N, Polhemus D, Veledar E, Lefer DJ, Quyyumi AA. Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol. J Clin Hypertens (Greenwich). 2016 Mar;18(3):223-31. doi: 10.1111/jch.12649. Epub 2015 Aug 19. |
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| ID | Type | URL | Comment |
|---|---|---|---|
| 26285691 | Publication | View IPD |
91 subjects were enrolled but 47 subjects were withdrawn prior to group assignment due to various factors, which included eligibility criteria, lost to follow-up, and withdrawal by subject.
Subjects recruited from the general medical clinics of The Emory Clinic, Emory University Hospital, and Grady Memorial Hospital between January 2010 through January 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nebivolol/Metoprolol XL | Subjects are randomized to Nebivolol 5mg and titrate to Nebivolol 10mg two weeks after drug initiation. Ten weeks after titration subjects will cross over to Metoprolol XL 50mg and titrate to Metoprolol XL 100mg two weeks after cross over. |
| FG001 | Metoprolol XL/Nebivolol | Subjects are randomized to Metoprolol XL 50mg and titrate to Metoprolol XL 100mg two weeks after drug initiation. Ten weeks after titration subjects will cross over to Nebivolol 5mg and titrate to Nebivolol 10mg two weeks after cross over. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period 1 (12 Weeks) |
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| Treatment Period 2 (12 Weeks) |
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Baseline population characteristics only account for subjects that completed the entire study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Nebivolol/Metoprolol XL | Subjects were randomized to Nebivolol 5mg and titrated to Nebivolol 10mg two weeks after drug initiation. Ten weeks after titration, subjects crossed over to Metoprolol XL 50mg and titrated to Metoprolol XL 100mg two weeks after cross over. |
| BG001 | Metoprolol XL/Nebivolol |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Endothelial Function Measured by Forearm Blood Flow (FBF) at 12 Weeks | Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute. | Posted | Mean | Standard Deviation | mL/100 mL/min | 12 weeks |
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Only subjects that were randomized into an arm with drug were included in the "at-risk participant" fields.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nebivolol/Metoprolol XL | Subjects were randomized to Nebivolol 5mg and titrated to Nebivolol 10mg two weeks after drug initiation. Ten weeks after titration, subjects crossed over to Metoprolol XL 50mg and titrated to Metoprolol XL 100mg two weeks after cross over. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Arshed A. Quyyumi | Emory University School of Medicine | 404-727-3655 | aquyyum@emory.edu |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000068577 | Nebivolol |
| D008790 | Metoprolol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Metoprolol XL | Drug | Subjects will be randomized to either nebivolol or metoprolol xl, and remain on the study drug for 10 weeks. They will then "cross over" to take 10 weeks of the comparator drug. |
|
| NOT COMPLETED |
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|
Subjects were randomized to Metoprolol XL 50mg and titrated to Metoprolol XL 100mg two weeks after drug initiation. Ten weeks after titration, subjects crossed over to Nebivolol 5mg and titrated to Nebivolol 10mg two weeks after cross over. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Subjects were randomized to Metoprolol XL 50mg and titrated to Metoprolol XL 100mg two weeks after drug initiation. Ten weeks after titration, subjects crossed over to Nebivolol 5mg and titrated to Nebivolol 10mg two weeks after cross over. |
|
|
| Primary | Endothelial Function Measured by Forearm Blood Flow (FBF) at 24 Weeks | Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute. | Posted | Mean | Standard Deviation | mL/100 mL/min | 24 weeks |
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|
| 0 |
| 23 |
| 0 |
| 23 |
| EG001 | Metoprolol XL/Nebivolol | Subjects were randomized to Metoprolol XL 50mg and titrated to Metoprolol XL 100mg two weeks after drug initiation. Ten weeks after titration, subjects crossed over to Nebivolol 5mg and titrated to Nebivolol 10mg two weeks after cross over. | 0 | 21 | 0 | 21 |
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| D000588 |
| Amines |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D020005 | Propanols |
| L-NMMA+TEA+ACh |
|
| L-NMMA+TEA+exercise |
|