Efficacy of Coreg CR and Lisinopril on Markers for Cardiovascular Functional and Structural Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy of Coreg CR and Lisinopril on Markers for Cardiovascular Functional and Structural Disease. DETECT (DEtection and Treatment of Early Cardiovascular Disease Trial)

Conditions
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Pre-hypertension

Intervention / Treatment
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* Drug: carvedilol phosphate
* Drug: lisinopril
* Drug: carvedilol phosphate and lisinopril
* Drug: placebo and placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Coreg CR + lisinopril | Drug: carvedilol phosphate and lisinopril<br>* 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<br>* Other names: Coreg CR (carvedilol phosphate);|
| Experimental: 2<br>Coreg CR + placebo | Drug: carvedilol phosphate<br>* Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months<br>* Other names: Coreg CR;|
| Experimental: 3<br>lisinopril + placebo | Drug: lisinopril<br>* tablets, 10mg once daily for 1 month, 20mg once daily for 8 months<br>|
| Placebo Comparator: 4<br>placebo + placebo | Drug: placebo and placebo<br>* capsule once daily for 9 months; dosage unknown<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and nine months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular disease prevention