Clinical trial NCT00108082: The CLEVER Study - Coreg And Left Ventricular Mass Regression
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertrophy, Left Ventricular
Keywords: left ventricular hypertrophy (LVH)
echocardiogram
left ventricular mass regression
cardiac MRI
left ventricular mass index (LVMI)hypertension
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-04-14
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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 outcomes:
measure: Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12
timeFrame: 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)
measure: Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12
timeFrame: 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)
measure: Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12
timeFrame: 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)
measure: Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12
timeFrame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used
measure: Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12
timeFrame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used)
measure: Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12
timeFrame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used)
measure: Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12
timeFrame: Baseline and Month 12 (If Month 12 data were not available, the LOCF was used)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Mobile
country: United States
facility: GSK Investigational Site
state: Alabama
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Peoria
country: United States
facility: GSK Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Sun City
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palo Alto
country: United States
facility: GSK Investigational Site
state: California
city: Poway
country: United States
facility: GSK Investigational Site
state: California
city: Sacremento
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Leandro
country: United States
facility: GSK Investigational Site
state: California
city: Santa Ana
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Newark
country: United States
facility: GSK Investigational Site
state: Delaware
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Altamonte Springs
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlantis
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Kissimmee
country: United States
facility: GSK Investigational Site
state: Florida
city: Longwood
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Ormond Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: GSK Investigational Site
state: Florida
city: Evanston
country: United States
facility: GSK Investigational Site
state: Illinois
city: Vernon Hills
country: United States
facility: GSK Investigational Site
state: Illinois
city: Fort Wayne
country: United States
facility: GSK Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Scarborough
country: United States
facility: GSK Investigational Site
state: Maine
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Columbia
country: United States
facility: GSK Investigational Site
state: Maryland
city: Pikesville
country: United States
facility: GSK Investigational Site
state: Maryland
city: Grand Rapids
country: United States
facility: GSK Investigational Site
state: Michigan
city: Edina
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Minneapolis
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Camden
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Williamsville
country: United States
facility: GSK Investigational Site
state: New York
city: Fayetteville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Hillsboro
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Allentown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Camp Hill
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Doylestown
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: West Grove
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Warwick
country: United States
facility: GSK Investigational Site
state: Rhode Island
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greer
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Knoxville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Danville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Roanoke
country: United States
facility: GSK Investigational Site
state: Virginia
city: Springfield
country: United States
facility: GSK Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: GSK Investigational Site
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1016/j.amjcard.2006.08.002. Epub 2006 Aug 28.
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.