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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Factorial Assignment

Study Primary Completion Date: September 2009

- 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.

Intervention(s) in this Clinical Trial

• Drug: carvedilol phosphate
  • Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months
• Drug: lisinopril
  • tablets, 10mg once daily for 1 month, 20mg once daily for 8 months
• Drug: 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

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Coreg CR + lisinopril
• Experimental: 2
  • Coreg CR + placebo
• Experimental: 3
  • lisinopril + placebo

Primary Measures

• The overall Rasmussen Disease Score (RDS) change from baseline to 9 months will be the primary end-point.
  • Time Frame: 9 months
    Safety Issue?: No

Secondary Measures

• Quantitative change in each of the RDS components from baseline to 9 months will serve as a secondary end-point. The 3-month data will provide early evidence for drug efficacy and will be analyzed similarly as a secondary end-point.
  • Time Frame: 3-9 months
    Safety Issue?: 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Minnesota

Overall Clinical Trial Officials and Contacts

Jay N Cohn, MD Principal Investigator Professor, University of Minnesota, Cardiology Division  

Overall Contact: Sara M Saul, PhD 612-626-5446 saul@umn.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00553969

Study ID Number: 0709M15829

ClinicalTrials.gov Identifier: NCT00553969

Health Authority: United States: Institutional Review Board