The CLEVER Study - Coreg And Left Ventricular Mass Regression

Study Overview
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Brief Summary
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This study is designed to compare the effects of COREG MR (carvedilol modified release formulation) to atenolol on indices of left ventricular dimensions when added to standardized angiotensin converting enzyme (ACE) inhibition, and to the effect of ACE inhibition alone. Subjects with LVH (left ventricular hypertrophy) and hypertension will be studied. The primary endpoint will be the change in left ventricular mass index (LVMI) characterized by magnetic resonance imaging (MRI) following 12 months of treatment. Secondary endpoints include the change in LV (left ventricular) mass, LV wall thickness, diastolic left ventricular filling parameters, and left ventricular ejection fraction by echocardiographic methods at Treatment Month 12. Composite outcomes and individual event data will also be evaluated by treatment group.

Detailed Description
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A Randomized, Double-Blind, Multi-Center Study Comparing the Effects of Carvedilol Modified Release Formulation (COREG MR) and Atenolol in Combination with and Compared to an Angiotensin Converting Enzyme Inhibitor (Lisinopril) on Left Ventricular Mass Regression in Hypertensive Patients with Left Ventricular Hypertrophy (LVH).

Official Title
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A Randomized, Double-Blind, Multi-Center Study Comparing the Effects of Carvedilol Modified Release Formulation (COREG MR) and Atenolol in Combination With and Compared to an Angiotensin Converting Enzyme Inhibitor (Lisinopril) on Left Ventricular Mass Regression in Hypertensive Patients With Left Ventricular Hypertrophy (LVH).

Conditions
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Hypertrophy, Left Ventricular

Intervention / Treatment
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* Drug: carvedilol MR
* Drug: atenolol
* Drug: lisinopril


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Stage 1 or Stage 2 hypertension. Left ventricular hypertrophy. Exclusion criteria: In atrial fibrillation. Takes beta-blocker for MI (myocardial infarction) or arrhythmia. Has uncontrolled diabetes, uncontrollable or symptomatic arrhythmias, unstable angina, second or third degree heart block, history of MI, COPD (chronic obstructive pulmonary disease), liver or kidney disease. Uses beta-2-agonists. Unable to undergo MRI (magnetic resonance imaging). Females of childbearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carvedilol CR<br>Carvedilol controlled release (CR) 20 to 80 mg once daily (OD) plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. (In the protocol, carvedilol CR was referred to as carvedilol modified-release [MR].) | Drug: carvedilol MR<br>* Study drug<br>* Other names: Carvedilol controlled release or modified release;Drug: lisinopril<br>* Comparator<br>* Other names: atenolol;|
| Experimental: Atenolol<br>Atenolol 50 to 100 mg OD plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. | Drug: atenolol<br>* Comparator<br>Drug: lisinopril<br>* Comparator<br>* Other names: atenolol;|
| Experimental: Lisinopril<br>Lisinopril 10 to 40 mg OD plus lisinopril 20 mg OD. Participants were titrated from the starting dosage to higher dosages until their blood pressure was controlled. Participants continued to receive lisinopril 20 mg OD throughout the study. | Drug: lisinopril<br>* Comparator<br>* Other names: atenolol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Magnetic Resonance Imaging (MRI) at Month 12 | LVMI was measured by MRI at Baseline and after 12 months of treatment/Month 12. A reduction in left ventricular mass, calculated as LVMI, of 5 g/m^2 was assumed to be clinically meaningful. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the Last Observation Carried Forward [LOCF] analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 | LVMIH was measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. LV mass depends on body size. One method of determining whether an individual has LV hypertrophy relates LV mass to height raised to a power of 2.7. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 | LV Mass was measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 | LVMI was measured by echogradiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 | LVMIH was measured by echogradiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was available) | 
| Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 | LV Mass was measured by echocardiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 | LV filling parameters, LV E-Volume and LV A-Volume, were measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. These filling parameters represent the volumes of blood filling the ventricle during the passive filling phase (E-volume) and the active filling phase caused by atrial contraction (A-volume). | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 | LV End Systolic and Diastolic Volumes and Ejection Fraction were measured by MRI at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. The ejection fraction is the fraction of the blood volume available at the end of diastole that is pumped out of the ventricules during systole. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 | LV End Systolic and Diastolic Volumes and Ejection Fraction were measured by echocardiography at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 | Systolic and Diastolic BP were measured at Baseline and after 12 months of treatment/Month 12. Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value. | Baseline and Month 12 (If Month 12 data were not available, the LOCF analysis, which includes data collected on or after Month 9 of treatment to Month 12 of treatment, was used) | 
| Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 | BNP concentration (picagram per milliter) was measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and was calculated as 100 x (exponent (mean change on log scale) -1) [Change is the Month 12 value (or value after 12 months of treatment) minus the Baseline value]. | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used | 
| Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 | CRP concentration (milligrams per deciliter) was measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and calculated as 100 x (exponent (mean change on log scale) - 1). [Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.] | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used) | 
| Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 | Plasma lipid concentrations (milligrams per deciliter) were measured at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and calculated as 100 x (exponent(mean change on log scale) - 1). [Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.] | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used) | 
| Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 | Urinary ACR (micrograms per milligram) was determined at Baseline and after 12 months of treatment/Month 12. Percentage change from Baseline was based on log transformed data and was calculated as 100 x (exponent (exponent (mean change on log scale) - 1. [Change in Baseline was calculated as Month 12 value (or value after 12 months of treatment) minus the Baseline value.] | Baseline and Month 12 (If Month 12 data were not available, the LOCF was used) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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left ventricular hypertrophy (LVH), echocardiogram, left ventricular mass regression, cardiac MRI, left ventricular mass index (LVMI)hypertension