The CLEVER Study - Coreg And Left Ventricular Mass Regression - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double-Blind, Parallel Assignment
Conditions:	Hypertension Left Ventricular Hypertrophy
Interventions:	Drug: carvedilol MR Drug: atenolol Drug: lisinopril

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Following screening, 413 participants were enrolled into the study to begin an open-label run-in phase with lisinopril 10 mg once daily (OD) for 1 week and then lisinopril 20 mg OD for 1 week. Of these participants, 287 were randomized to 1 of the 3 treatment regimens.

Reporting Groups

	Description
Carvedilol CR	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].)
Atenolol	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.
Lisinopril	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.

Participant Flow: Overall Study

	Carvedilol CR	Atenolol	Lisinopril
STARTED	91	100	96
COMPLETED	53^[1]	68^[2]	53^[3]
NOT COMPLETED	38	32	43
Adverse Event	14	12	17
Lost to Follow-up	6	3	7
Consent withdrawn	3	3	5
Protocol Violation	1	2	0
Lack of Efficacy	3	1	2
Amendment 4: > Month 12	5	7	5
Woman of child-bearing potential	2	0	2
Incorrectly randomized	0	0	2
Non-compliance	1	0	2
Other	3	4	1

[1]	Per protocol Amendment 4, participants who had completed Month 12 prior to amendment were withdrawn.
[2]	Per protocol Amendment 4, participants who had completed Month 12 prior to amendment were withdrawn.
[3]	Per protocol Amendment 4, participants who had completed Month 12 prior to amendment were withdrawn.

Baseline Characteristics

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Reporting Groups

	Description
Carvedilol CR	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].)
Atenolol	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.
Lisinopril	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.

Baseline Measures

	Carvedilol CR	Atenolol	Lisinopril	Total
Number of Participants [units: participants]	91	100	96	287
Age [units: years] Mean ± Standard Deviation	56.6 ± 10.53	57.4 ± 10.95	55.9 ± 10.09	56.7 ± 10.52
Gender [units: participants]
Female	40	41	47	128
Male	51	59	49	159
Race/Ethnicity, Customized [units: participants]
African American/African Heritage	17	26	17	60
American Indian/Alaska Native	0	1	1	2
Asian	2	1	0	3
White/Caucasian	67	67	72	206
Arabic/North African Heritage	1	0	1	2
Mixed Race	1	0	1	2
Not Reported	3	5	4	12

Outcome Measures

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1. 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 [ 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) ]

Show Outcome Measure 1

2. Secondary:

Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 [ 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) ]

Show Outcome Measure 2

3. Secondary:

Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 [ 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) ]

Show Outcome Measure 3

4. Secondary:

Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 [ 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) ]

Show Outcome Measure 4

5. Secondary:

Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 [ 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) ]

Show Outcome Measure 5

6. Secondary:

Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 [ 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) ]

Show Outcome Measure 6

7. Secondary:

Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 [ 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) ]

Show Outcome Measure 7

8. Secondary:

Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 [ 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) ]

Show Outcome Measure 8

9. Secondary:

Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 [ 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) ]

Show Outcome Measure 9

10. Secondary:

Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 [ 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) ]

Show Outcome Measure 10

11. Secondary:

Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 [ Month 12 (If Month 12 data were not available, the LOCF was used ]

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12. Secondary:

Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 [ Month 12 (If Month 12 data were not available, the LOCF was used) ]

Show Outcome Measure 12

13. Secondary:

Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 [ Month 12 (If Month 12 data were not available, the LOCF was used) ]

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14. Secondary:

Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 [ Month 12 (If Month 12 data were not available, the LOCF was used) ]

Show Outcome Measure 14

Serious Adverse Events

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Reporting Groups

	Description
Carvedilol CR	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].)
Atenolol	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.
Lisinopril	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.

Serious Adverse Events

	Carvedilol CR	Atenolol	Lisinopril
Total, serious adverse events
# participants affected	4	6	12
Cardiac disorders
Atrial fibrillation ^†^A # participants affected / at risk	1/91 (1.10%)	0/100 (0.00%)	2/96 (2.08%)
Acute coronary syndrome ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Coronary artery disease ^†^A # participants affected / at risk	1/91 (1.10%)	0/100 (0.00%)	0/96 (0.00%)
Myocardial infarction ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Eye disorders
Vision blurred ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Gastrointestinal disorders
Abdominal pain ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Inguinal hernia obstructive ^†^A # participants affected / at risk	0/91 (0.00%)	1/100 (1.00%)	0/96 (0.00%)
Pancreatitis ^†^A # participants affected / at risk	0/91 (0.00%)	1/100 (1.00%)	0/96 (0.00%)
General disorders
Non-cardiac chest pain ^†^A # participants affected / at risk	0/91 (0.00%)	2/100 (2.00%)	1/96 (1.04%)
Chest pain ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Immune system disorders
Drug hypersensitivity ^†^A # participants affected / at risk	0/91 (0.00%)	1/100 (1.00%)	0/96 (0.00%)
Metabolism and nutrition disorders
Gout ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion ^†^A # participants affected / at risk	0/91 (0.00%)	1/100 (1.00%)	0/96 (0.00%)
Muscular weakness ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Nervous system disorders
Dizziness ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	2/96 (2.08%)
Transient ischemic attack ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	2/96 (2.08%)
Headache ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Neuropathy peripheral ^†^A # participants affected / at risk	1/91 (1.10%)	0/100 (0.00%)	0/96 (0.00%)
Syncope ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)
Psychiatric disorders
Depression ^†^A # participants affected / at risk	1/91 (1.10%)	0/100 (0.00%)	0/96 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary mass ^†^A # participants affected / at risk	0/91 (0.00%)	0/100 (0.00%)	1/96 (1.04%)

^†	Indicates events were collected by systematic assessment.
^A	Term from vocabulary, MedDRA

Other Adverse Events

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More Information

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Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	COR100216
Study First Received:	April 13, 2005
Results First Received:	August 13, 2009
Last Updated:	September 30, 2009
ClinicalTrials.gov Identifier:	NCT00108082 History of Changes
Health Authority:	United States: Food and Drug Administration