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

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00553969
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 101
• Location: 1
• Arms: 4
• Duration (Months): 37
• Patients Per Site Per Month: 2.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pre-hypertension	Drug: carvedilol phosphate; Drug: lisinopril; Drug: carvedilol phosphate and lisinopril; Drug: placebo and placebo	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Dec 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota, Variety Club Research Center 102	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• University of Minnesota
• GlaxoSmithKline

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT00553969
• Other Study ID Numbers: 0709M15829
• First Posted: Nov 6, 2007
• Last Update Posted: Apr 24, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by University of Minnesota: cardiovascular disease prevention
• Additional relevant MeSH terms: Prehypertension; Carvedilol; Lisinopril

Study Results

Participant Flow

Arm/Group Title	1 Coreg CR + Lisinopril	2 Coreg CR + Placebo	3 Lisinopril + Placebo	4 Placebo + Placebo
Arm/Group Description	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	Coreg CR + placebo carvedilol phosphate : Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months	lisinopril + placebo lisinopril : tablets, 10mg once daily for 1 month, 20mg once daily for 8 months
Period Title: Overall Study
STARTED	31	24	22	24
COMPLETED	23	24	21	23
NOT COMPLETED	8	0	1	1

Baseline Characteristics

Arm/Group Title	1 Coreg CR + Lisinopril	2 Coreg CR + Placebo	3 Lisinopril + Placebo	4 Placebo + Placebo	Total
Arm/Group Description	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	Coreg CR + placebo carvedilol phosphate : Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months	lisinopril + placebo lisinopril : tablets, 10mg once daily for 1 month, 20mg once daily for 8 months	Total of all reporting groups
Overall Participants	23	24	21	23	91
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	24 100%	21 100%	23 100%	91 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (13)	53 (10)	53 (10)	51 (13)	52.25 (11.5)
Sex: Female, Male (Count of Participants)
Female	6 26.1%	7 29.2%	5 23.8%	8 34.8%	26 28.6%
Male	17 73.9%	17 70.8%	16 76.2%	15 65.2%	65 71.4%
Region of Enrollment (participants) [Number]
United States	23 100%	24 100%	21 100%	23 100%	91 100%

Outcome Measures

1. Primary Outcome

Title	Change in Disease Score (DS) Among the Treatment Groups
Description	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

Outcome Measure Data

Analysis Population Description

Calculation for change is the value at the later time point minus the value at the earlier time point.

Arm/Group Title	1 Coreg CR + Lisinopril	2 Coreg CR + Placebo	3 Lisinopril + Placebo	4 Placebo + Placebo
Arm/Group Description	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	Coreg CR + placebo carvedilol phosphate : Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months	lisinopril + placebo lisinopril : tablets, 10mg once daily for 1 month, 20mg once daily for 8 months
Measure Participants	23	24	21	23
Mean (Standard Deviation) [Overall Rasmussen Disease Score Change]	-2.48 (1.9)	-2.29 (2.3)	-2.38 (2.6)	-0.96 (1.5)

Adverse Events

Arm/Group Title	1 Coreg CR + Lisinopril		2 Coreg CR + Placebo		3 Lisinopril + Placebo		4 Placebo + Placebo
Arm/Group Description	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		Coreg CR + placebo carvedilol phosphate : Extended release capsules, 20mg once daily for 1 month, 40mg once daily for 8 months		lisinopril + placebo lisinopril : tablets, 10mg once daily for 1 month, 20mg once daily for 8 months
All Cause Mortality
	1 Coreg CR + Lisinopril		2 Coreg CR + Placebo		3 Lisinopril + Placebo		4 Placebo + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	1 Coreg CR + Lisinopril		2 Coreg CR + Placebo		3 Lisinopril + Placebo		4 Placebo + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/24 (0%)		1/22 (4.5%)		0/24 (0%)
Vascular disorders
stroke	0/31 (0%)		0/24 (0%)		1/22 (4.5%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	1 Coreg CR + Lisinopril		2 Coreg CR + Placebo		3 Lisinopril + Placebo		4 Placebo + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/24 (0%)		0/22 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.