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

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

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.

	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Consent withdrawn	3	3	5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[1]	Per protocol Amendment 4, participants who had completed Month 12 prior to amendment were withdrawn.
[2]	Per protocol Amendment 4, participants who had completed Month 12 prior to amendment were withdrawn.
[3]	Per protocol Amendment 4, participants who had completed Month 12 prior to amendment were withdrawn.

	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

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) ]

Measure Type	Primary
Measure Title	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
Measure Description	LVMI was measured by MRI at Baseline and after 12 months of treatment/Month12. A reduction in left ventricular mass, calculated as LVMI, of 5 g/m2 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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	60	76	59
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 [units: grams per meters squared (g/m2)] Mean ± Standard Error	-6.34 ± 0.850	-6.67 ± 0.756	-7.94 ± 0.850

Statistical Analysis 1 for 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

Groups ^[1]	Carvedilol CR vs. Atenolol
Method ^[2]	ANCOVA
P Value ^[3]	0.7651
Mean Difference (Final Values) ^[4]	0.33
95% Confidence Interval	( -1.83 to 2.49 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The null hypotheses (tested hierarchically) were that the effect of carvedilol CR + lisinopril on LV mass regression was no different than the effect of atenolol + lisinopril, and that the effect of carvedilol CR + lisinopril was no different than the effect of lisinopril + lisinopril. The primary analysis was based on an analysis of covariance (ANCOVA) with a model adjusting for treatment, stratification by hypertension class, region, and baseline value, at a 0.05 level of significance.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for 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

Groups ^[1]	Carvedilol CR vs. Lisinopril
Method ^[2]	ANCOVA
P Value ^[3]	0.1711
Mean Difference (Final Values) ^[4]	1.60
95% Confidence Interval	( -0.70 to 3.90 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	60	76	59
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12 [units: grams per meters raised to 2.7 (g/m2.7)] Mean ± Standard Error	-3.19 ± 0.407	-3.37 ± 0.361	-3.98 ± 0.407

No statistical analysis provided for Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by MRI at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	60	76	59
Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12 [units: grams (g)] Mean ± Standard Error	-13.74 ± 1.732	-14.17 ± 1.540	-17.17 ± 1.734

No statistical analysis provided for Model-adjusted Mean Change From Baseline in Left Ventricular (LV) Mass as Measured by MRI at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	61	71	59
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12 [units: grams per meters squared (g/m2)] Mean ± Standard Error	-20.35 ± 4.027	-20.06 ± 3.672	-18.48 ± 3.998

No statistical analysis provided for Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed (LVMI) by Body Surface Area as Measured by Echocardiography at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	61	71	59
Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12 [units: grams per meters raised to 2.7 (g/m2.7)] Mean ± Standard Error	-11.78 ± 2.292	-12.51 ± 2.100	-11.61 ± 2.280

No statistical analysis provided for Model-adjusted Mean Change From Baseline in Left Ventricular Mass Indexed by Height (LVMIH) as Measured by Echocardiography at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	61	71	59
Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12 [units: grams] Mean ± Standard Error	-45.76 ± 8.338	-40.56 ± 7.645	-38.58 ± 8.296

No statistical analysis provided for Model-adjusted Mean Change From Baseline in LV Mass as Measured by Echocardiography at Month 12

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) ]

Measure Type	Secondary
Measure Title	Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	48	54	41
Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12 [units: milliliters (mL)] Mean ± Standard Error
LV E-volume	0.364 ± 2.2853	6.763 ± 2.3870	-3.406 ± 2.8779
LV A-volume	-0.513 ± 1.3624	-0.565 ± 1.5154	1.088 ± 1.5630

No statistical analysis provided for Mean Change From Baseline in LV Filling Parameters as Measured by MRI at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	60	76	59
Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12 [units: milliliters (mL)] Mean ± Standard Error
LV End Systolic Volume	-1.44 ± 1.578	-4.29 ± 1.397	-3.04 ± 1.581
LV End Diastolic Volume	-2.86 ± 2.848	-2.45 ± 2.522	-7.45 ± 2.858
LV Ejection Fraction	0.08 ± 0.685	2.16 ± 0.607	-0.01 ± 0.685

No statistical analysis provided for Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by MRI at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid echocardiogram at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	60	76	59
Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12 [units: Volumes measured in milliliters (mL)] Mean ± Standard Error
LV End Systolic Volume	-3.38 ± 2.067	-4.74 ± 1.892	-5.34 ± 2.086
LV End Diastolic Volume	-3.07 ± 3.389	-3.64 ± 3.108	-9.37 ± 3.420
LV Ejection Fraction	1.03 ± 0.751	2.33 ± 0.687	0.63 ± 0.756

No statistical analysis provided for Model-adjusted Mean Change From Baseline in LV End Systolic and Diastolic Volumes and Ejection Fraction as Measured by Echocardiography at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12
Measure Description	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.
Time Frame	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)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid MRI at Baseline and Month 12 (LOCF on or after Month 9 to Month 12)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	60	76	59
Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12 [units: mmHg (millimeters of mercury)] Mean ± Standard Error
Systolic blood pressure	-21.32 ± 1.755	-21.12 ± 1.535	-22.53 ± 1.708
Diastolic blood pressure	-12.77 ± 1.103	-14.05 ± 0.976	-11.13 ± 1.117

No statistical analysis provided for Model-adjusted Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Month 12

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 ]

Measure Type	Secondary
Measure Title	Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12
Measure Description	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].
Time Frame	Month 12 (If Month 12 data were not available, the LOCF was used
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	34	42	33
Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12 [units: percentage] Geometric Mean ( 95% Confidence Interval )	51.7 ( 13.2 to 103.2 )	48.3 ( 13.0 to 94.7 )	-39.1 ( -54.3 to -19.0 )

No statistical analysis provided for Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed B-type Natriuretic Peptide (BNP) at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12
Measure Description	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.]
Time Frame	Month 12 (If Month 12 data were not available, the LOCF was used)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	48	66	53
Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 12 [units: percentage] Geometric Mean ( 95% Confidence Interval )	-10.63 ( -27.41 to 10.02 )	-3.22 ( -18.82 to 15.38 )	2.70 ( -15.88 to 25.37 )

No statistical analysis provided for Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed C-Reactive Protein (CRP) at Month 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) ]

Measure Type	Secondary
Measure Title	Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12
Measure Description	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.]
Time Frame	Month 12 (If Month 12 data were not available, the LOCF was used)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	83	92	90
Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12 [units: percentage] Geometric Mean ( 95% Confidence Interval )
Total cholesterol	0.7 ( -3.3 to 4.9 )	-1.3 ( -4.7 to 2.3 )	-1.7 ( -5.5 to 2.3 )
Low-density lipid cholesterol	0.0 ( -6.5 to 7.0 )	-4.0 ( -9.6 to 1.8 )	-2.7 ( -9.0 to 4.1 )
High-density lipid cholesterol	-4.3 ( -7.7 to 0.7 )	-4.7 ( -7.7 to -1.6 )	-1.5 ( -4.9 to 2.1 )
Triglycerides	11.0 ( 2.0 to 20.9 )	7.1 ( -0.7 to 15.4 )	6.2 ( -2.4 to 15.5 )

No statistical analysis provided for Percentage Change From Baseline in Log Transformed Lipid Parameters at Month 12

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) ]

Measure Type	Secondary
Measure Title	Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12
Measure Description	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.]
Time Frame	Month 12 (If Month 12 data were not available, the LOCF was used)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants who had a valid measurements at Baseline and Month 12 (LOCF)

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.

Measured Values

	Carvedilol CR	Atenolol	Lisinopril
Number of Participants Analyzed [units: participants]	40	51	38
Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12 [units: percentage] Geometric Mean ( 95% Confidence Interval )	-27.1 ( -39.9 to -11.6 )	-20.1 ( -32.4 to -5.5 )	-21.5 ( -35.2 to -4.8 )

No statistical analysis provided for Model-adjusted Ratio to Baseline as Percentage Change From Baseline in Log Transformed Albumin Creatinine Ratio (ACR) at Month 12

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