Pre-hypertension
Conditions
Keywords
cardiovascular disease prevention
Brief summary
This study will examine the individual and combined effects of Coreg CR and lisinopril, on cardiovascular health as measured by Rasmussen Disease Score (RDS) in a blinded, placebo controlled comparison over a 9-month study period. Patients to be randomized will have pre-hypertensive blood pressures that do not require anti-hypertensive therapy and at least one additional cardiovascular risk factor.
Detailed description
* This study will compare the effect of Coreg CR and lisinopril, separately and together, on Rasmussen Disease Score in a controlled study with an inactive substance (placebo). * Study patients will have pre-hypertensive (slightly elevated) blood pressures not requiring therapy. * Lisinopril is an angiotensin converting enzyme (ACE) inhibitor. Angiotensin is a chemical that is made by the body continuously. Angiotensin narrows blood vessels and thereby maintains (elevates) blood pressure. When the enzyme is blocked by lisinopril, angiotensin cannot be converted into its active form. As a result, blood pressure is lowered. Lisinopril is a drug that has been approved for use by the U.S. Food and Drug Administration (FDA) and health authorities for the treatment of high blood pressure and heart failure. * Coreg CR is a once-a-day heart medication that is part of a class of drugs known as beta-blockers. Beta-blockers prevent beta-adrenergic substances such as adrenaline from activating parts of the nervous system, including the heart. Beta-blockers therefore relieve stress on the heart by slowing heart beat, decreasing the force of heart muscle contractions, and reducing blood pressure. Coreg has also been approved by the FDA for the treatment of hypertension and various other cardiovascular conditions. * It is possible that the beta blocker could increase the benefits of the ACE inhibitor by inhibiting renin production, which is an important step in angiotensin production. These two drugs may act together to provide even more protection to blood vessels and the heart.
Interventions
DRUGcarvedilol phosphate
Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months
DRUGlisinopril
tablets, 10mg once daily for 1 month, 20mg once daily for 8 months
DRUGcarvedilol phosphate and lisinopril
carvedilol phosphate = extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months; lisinopril= tablets, 10mg once daily for 1 month, 20mg once daily for 8 months
DRUGplacebo and placebo
capsule once daily for 9 months; dosage unknown
Sponsors
GlaxoSmithKline
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females \> 18 years old with pre-hypertensive or borderline blood pressures (systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg) deemed not to need antihypertensive therapy. Subjects must also have one additional risk factor for cardiovascular disease, including: * LDL \> 130 and \< 160 mg/dL * HDL \< 40 mg/dL * Fasting blood sugar \>100 and \< 126 mg/dL * Body mass index ≥ 30 * Smoker * Family history of premature heart disease or hypertension
Exclusion criteria
* Patients with a history of cardiac, cerebral or other vascular events within the previous 6 months will be excluded. Other exclusions include background therapy with a beta blocker or ACE inhibitor therapy, known or suspected intolerance to beta blockers or ACE inhibitors, angiotensin receptor blocker therapy, or diabetes. Pregnant or lactating women, and women of child-bearing age who are not using an acceptable form of contraception are also excluded from this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Disease Score (DS) Among the Treatment Groups | Baseline and nine months | Rasmussen Disease Score (RDS) Change From Baseline to 9 Months A score of six or higher on these tests means the patient likely has plaque build-up in the arteries, or atherosclerosis, while a score of three to five suggests that such a problem may be developing. A score of two or less signals a patient is fine but should return in the future for another test. The method detects disease at the earliest moment, before the traditionally used calcium score would show any signs of trouble. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 Coreg CR + Lisinopril Coreg CR + lisinopril
carvedilol phosphate and lisinopril : carvedilol phosphate = extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months; lisinopril= tablets, 10mg once daily for 1 month, 20mg once daily for 8 months | 23 |
| 2 Coreg CR + Placebo Coreg CR + placebo
carvedilol phosphate : Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months | 24 |
| 3 Lisinopril + Placebo lisinopril + placebo
lisinopril : tablets, 10mg once daily for 1 month, 20mg once daily for 8 months | 21 |
| 4 Placebo + Placebo | 23 |
| Total | 91 |
Baseline characteristics
| Characteristic | 2 Coreg CR + Placebo | 3 Lisinopril + Placebo | 1 Coreg CR + Lisinopril | 4 Placebo + Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 21 Participants | 23 Participants | 23 Participants | 91 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 10 | 53 years STANDARD_DEVIATION 10 | 52 years STANDARD_DEVIATION 13 | 51 years STANDARD_DEVIATION 13 | 52.25 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment United States | 24 participants | 21 participants | 23 participants | 23 participants | 91 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 6 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 17 Participants | 15 Participants | 65 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 31 | 0 / 24 | 0 / 22 | 0 / 24 |
| serious Total, serious adverse events | 0 / 31 | 0 / 24 | 1 / 22 | 0 / 24 |
Outcome results
Primary
Change in Disease Score (DS) Among the Treatment Groups
Rasmussen Disease Score (RDS) Change From Baseline to 9 Months A score of six or higher on these tests means the patient likely has plaque build-up in the arteries, or atherosclerosis, while a score of three to five suggests that such a problem may be developing. A score of two or less signals a patient is fine but should return in the future for another test. The method detects disease at the earliest moment, before the traditionally used calcium score would show any signs of trouble.
Time frame: Baseline and nine months
Population: Calculation for change is the value at the later time point minus the value at the earlier time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1 Coreg CR + Lisinopril | Change in Disease Score (DS) Among the Treatment Groups | -2.48 Overall Rasmussen Disease Score Change | Standard Deviation 1.9 |
| 2 Coreg CR + Placebo | Change in Disease Score (DS) Among the Treatment Groups | -2.29 Overall Rasmussen Disease Score Change | Standard Deviation 2.3 |
| 3 Lisinopril + Placebo | Change in Disease Score (DS) Among the Treatment Groups | -2.38 Overall Rasmussen Disease Score Change | Standard Deviation 2.6 |
| 4 Placebo + Placebo | Change in Disease Score (DS) Among the Treatment Groups | -0.96 Overall Rasmussen Disease Score Change | Standard Deviation 1.5 |