The CLEVER Study - Coreg And Left Ventricular Mass Regression

Hypertrophy, Left Ventricular Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00108082
• Other study ID #: COR100216
• Status: Completed
• Phase: Phase 3
• First received: April 13, 2005
• Last updated: November 5, 2015
• Start date: January 2005
• Est. completion date: August 2008

Study information

• Verified date: November 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 287
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertrophy
• Hypertrophy, Left Ventricular

Intervention

Drug:
• carvedilol MR
Study drug
• atenolol
Comparator
• lisinopril
Comparator

Locations

Country	Name	City	State
United States	GSK Investigational Site	Allentown	Pennsylvania
United States	GSK Investigational Site	Altamonte Springs	Florida
United States	GSK Investigational Site	Atlantis	Florida
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Buffalo	New York
United States	GSK Investigational Site	Camden	New Jersey
United States	GSK Investigational Site	Camp Hill	Pennsylvania
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Columbia	South Carolina
United States	GSK Investigational Site	Danville	Virginia
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Doylestown	Pennsylvania
United States	GSK Investigational Site	Edina	Minnesota
United States	GSK Investigational Site	Evanston	Illinois
United States	GSK Investigational Site	Fayetteville	North Carolina
United States	GSK Investigational Site	Fort Wayne	Indiana
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Grand Rapids	Michigan
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Greer	South Carolina
United States	GSK Investigational Site	Hillsboro	Oregon
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Kingsport	Tennessee
United States	GSK Investigational Site	Kissimmee	Florida
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Longwood	Florida
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Minneapolis	Minnesota
United States	GSK Investigational Site	Mobile	Alabama
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newark	Delaware
United States	GSK Investigational Site	Ormond Beach	Florida
United States	GSK Investigational Site	Palo Alto	California
United States	GSK Investigational Site	Pembroke Pines	Florida
United States	GSK Investigational Site	Peoria	Arizona
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Pikesville	Maryland
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Poway	California
United States	GSK Investigational Site	Roanoke	Virginia
United States	GSK Investigational Site	Sacremento	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Leandro	California
United States	GSK Investigational Site	Santa Ana	California
United States	GSK Investigational Site	Scarborough	Maine
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	Springfield	Virginia
United States	GSK Investigational Site	Sun City	Arizona
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Vernon Hills	Illinois
United States	GSK Investigational Site	Warwick	Rhode Island
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	West Grove	Pennsylvania
United States	GSK Investigational Site	Williamsville	New York
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bakris GL, Tarka EA, Waterhouse B, Goulding MR, Madan A, Anderson KM, St John Sutton M, Miller AB, Reichek N. Cardiovascular risk factors in hypertension: rationale and design of studies to investigate the effects of controlled-release carvedilol on regression of left ventricular hypertrophy and lipid profile. Am J Cardiol. 2006 Oct 2;98(7A):46L-52L. Epub 2006 Aug 28. Erratum in: Am J Cardiol. 2007 Mar 15;99(6):878. St John Sutton, Martin [added]; Miller, Alan B [added]; Reichek, Nathaniel [added]. Am J Cardiol. 2007 Aug 1;100(3):562. — View Citation

Miller AB, Reichek N, St John Sutton M, Iyengar M, Henderson LS, Tarka EA, Bakris GL. Importance of blood pressure control in left ventricular mass regression. J Am Soc Hypertens. 2010 Nov-Dec;4(6):302-10. doi: 10.1016/j.jash.2010.09.003. Epub 2010 Oct 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No