Research Study To Test Carvedilol CR + Lisinopril Versus Lisinopril + Placebo In Patients With High Blood Pressure

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00624065
• Collaborator: (none)
• Enrollment: 348
• Locations: 76
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Randomized, double-blind, parallel group, multicenter study of subjects with Stage 1 or 2 essential hypertension who are not at target blood pressure (<140/90mmHg) at Baseline. Subjects will be randomized to receive either carvedilol CR + lisinopril or lisinopril + placebo. Subjects will be uptitrated over a 6 week period until target blood pressure (<140/90mmHg) is met. The primary objective of the study is to compare the proportion of subjects who achieve target blood pressure after 6 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: carvedilol controlled release/lisinopril; Drug: lisinopril + placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 348 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: COR111096, A Randomized, Double-Blind, Active-Controlled, Parallel Group, Multicenter Study Comparing the Proportion of Subjects With Stage 1 or 2 Essential Hypertension Who Achieve Target Blood Pressure While Receiving Either Carvedilol CR + Lisinopril or Lisinopril Monotherapy
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: carvedilol CR + lisinopril	Drug: carvedilol controlled release/lisinopril; carvedilol CR + lisinopril given as separate pills
Active Comparator: lisinopril + placebo	Drug: lisinopril + placebo; lisinopril plus placebo to match carvedilol CR

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Mean Sitting Cuff Blood Pressure <140/90 mmHg at the End of 6 Weeks of Treatment [Week 6]

   Sitting cuff blood pressure was calculated as the mean of three measurements taken approximately 2 minutes apart, and before the morning dose.

Secondary Outcome Measures

1. Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6 [Baseline and Week 6]

   Mean change was calculated as Week 6 values minus Baseline values.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female age 18-80 years; stage 1 or 2 hypertension currently receiving 0 or 1 antihypertensive medication; mean sitting systolic blood pressure >/=140mmHg to </=170mmHg, or mean sitting diastolic blood pressure >/=90 to </=105mmHg. Subjects taking one hypertensive medication had their medication withdrawn and entered a wash-out phase prior to randomization.

Exclusion Criteria:

• Subject taking two or more antihypertensive medications, known contraindication to angiotensin-converting enzyme (ACE) inhibitors or alpha- or beta-blocker therapy, subject has Type 1 or Type 2 diabetes

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Mobile	Alabama	United States	36617
2	GSK Investigational Site	Chandler	Arizona	United States	77030
3	GSK Investigational Site	Glendale	Arizona	United States	85308
4	GSK Investigational Site	Goodyear	Arizona	United States	85395
5	GSK Investigational Site	Litchifield Park/Arizona	Arizona	United States	85340
6	GSK Investigational Site	Phoenix	Arizona	United States	85032
7	GSK Investigational Site	Tucson	Arizona	United States	85745
8	GSK Investigational Site	Anaheim	California	United States	92801
9	GSK Investigational Site	Beuna Park	California	United States	90620
10	GSK Investigational Site	Fountain Valley	California	United States	92708
11	GSK Investigational Site	Poway	California	United States	92064
12	GSK Investigational Site	San Ramon	California	United States	94583
13	GSK Investigational Site	Tustin	California	United States	92780
14	GSK Investigational Site	Vista	California	United States	92081
15	GSK Investigational Site	Coral Gables	Florida	United States	33134
16	GSK Investigational Site	Deland	Florida	United States	32720
17	GSK Investigational Site	Fort Lauderdale	Florida	United States	33308
18	GSK Investigational Site	Hollywood	Florida	United States	33023
19	GSK Investigational Site	Miami	Florida	United States	33156
20	GSK Investigational Site	Pembroke Pines	Florida	United States	33024
21	GSK Investigational Site	Tamarac	Florida	United States	33321
22	GSK Investigational Site	West Palm Beach	Florida	United States	33409
23	GSK Investigational Site	Atlanta	Georgia	United States	30342
24	GSK Investigational Site	Savannah	Georgia	United States	31406
25	GSK Investigational Site	Nampa	Idaho	United States	83686
26	GSK Investigational Site	Aurora	Illinois	United States	60504
27	GSK Investigational Site	Chicago	Illinois	United States	60607
28	GSK Investigational Site	Gillespie	Illinois	United States	62033
29	GSK Investigational Site	Elkhart	Indiana	United States	46514
30	GSK Investigational Site	Indianapolis	Indiana	United States	46250
31	GSK Investigational Site	Indianapolis	Indiana	United States	46260
32	GSK Investigational Site	Wichita	Kansas	United States	67205
33	GSK Investigational Site	Wichita	Kansas	United States	67207
34	GSK Investigational Site	Paducah	Kentucky	United States	42003
35	GSK Investigational Site	Slidell	Louisiana	United States	70458
36	GSK Investigational Site	Columbia	Maryland	United States	21045
37	GSK Investigational Site	Butte	Montana	United States	59701
38	GSK Investigational Site	Omaha	Nebraska	United States	68134
39	GSK Investigational Site	Las Vegas	Nevada	United States	89016
40	GSK Investigational Site	Las Vegas	Nevada	United States	89119
41	GSK Investigational Site	Albuquerque	New Mexico	United States	87102
42	GSK Investigational Site	Buffalo	New York	United States	14209
43	GSK Investigational Site	Buffalo	New York	United States	14215
44	GSK Investigational Site	East Syracuse	New York	United States	13057
45	GSK Investigational Site	New York	New York	United States	10075
46	GSK Investigational Site	Westfield	New York	United States	14787
47	GSK Investigational Site	Raleigh	North Carolina	United States	27609
48	GSK Investigational Site	Fargo	North Dakota	United States	58103
49	GSK Investigational Site	Cincinnati	Ohio	United States	45219
50	GSK Investigational Site	Corvallis	Oregon	United States	97330
51	GSK Investigational Site	Altoona	Pennsylvania	United States	16602
52	GSK Investigational Site	Havertown	Pennsylvania	United States	19083
53	GSK Investigational Site	Jersey Shore	Pennsylvania	United States	17740
54	GSK Investigational Site	Lansdale	Pennsylvania	United States	19446
55	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19154
56	GSK Investigational Site	Columbia	South Carolina	United States	29201
57	GSK Investigational Site	Columbia	South Carolina	United States	29204
58	GSK Investigational Site	Manning	South Carolina	United States	29102
59	GSK Investigational Site	Johnson City	Tennessee	United States	37601
60	GSK Investigational Site	Austin	Texas	United States	78705
61	GSK Investigational Site	Georgetown	Texas	United States	78626
62	GSK Investigational Site	Grand Prairie	Texas	United States	75052
63	GSK Investigational Site	Houston	Texas	United States	77081
64	GSK Investigational Site	San Antonio	Texas	United States	78224
65	GSK Investigational Site	San Antonio	Texas	United States	78229
66	GSK Investigational Site	Sugar Land	Texas	United States	77479
67	GSK Investigational Site	Draper	Utah	United States	84020
68	GSK Investigational Site	Magna	Utah	United States	84044
69	GSK Investigational Site	Salt Lake City	Utah	United States	84109
70	GSK Investigational Site	Salt Lake City	Utah	United States	84121
71	GSK Investigational Site	Sandy	Utah	United States	84094
72	GSK Investigational Site	Bellingham/Washington	Washington	United States	98226
73	GSK Investigational Site	Gig Harbor	Washington	United States	98335
74	GSK Investigational Site	Olympia	Washington	United States	98502-8151
75	GSK Investigational Site	Tacoma	Washington	United States	98405
76	GSK Investigational Site	Beloit	Wisconsin	United States	53511

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• GSK has submitted manuscripts of these study results to peer-reviewed scientific journals which were not accepted for publication. GSK is providing the attached study results summary with a conclusion.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00624065
• Other Study ID Numbers: COR111096
• First Posted: Feb 26, 2008
• Last Update Posted: Dec 28, 2016
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: target blood pressure; hypertension; COREG CR; carvedilol CR; Stage 1 or 2 essential hypertension; lisinopril
• Additional relevant MeSH terms: Hypertension; Essential Hypertension; Carvedilol; Lisinopril

Study Results

Participant Flow

Arm/Group Title	Lisinopril	Carvedilol CR + Lisinopril
Arm/Group Description	Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Period Title: Overall Study
STARTED	216	216
COMPLETED	197	192
NOT COMPLETED	19	24

Baseline Characteristics

Arm/Group Title	Lisinopril	Carvedilol CR + Lisinopril	Total
Arm/Group Description	Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)	Total of all reporting groups
Overall Participants	216	216	432
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.0 (11.9)	54.1 (9.8)	54.1 (10.9)
Gender (Count of Participants)
Female	95 44%	95 44%	190 44%
Male	121 56%	121 56%	242 56%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage (AA/AH)	45 20.8%	29 13.4%	74 17.1%
American Indian or Alaska Native	1 0.5%	2 0.9%	3 0.7%
Japanese/East Asian/South East Asian Heritage	16 7.4%	6 2.8%	22 5.1%
Mixed Asian Heritage	1 0.5%	0 0%	1 0.2%
White	150 69.4%	178 82.4%	328 75.9%
AA/AH & American Indian or Alaska Native	2 0.9%	0 0%	2 0.5%
AA/AH & American Indian or Alaska Native & White	1 0.5%	0 0%	1 0.2%
AA/AH & White	0 0%	1 0.5%	1 0.2%
Baseline Blood Pressure (mm/Hg) [Mean (Standard Deviation) ]
Baseline Sitting Systolic Blood Pressure (SBP)	149.8 (10.25)	148.8 (10.30)	149.3 (10.27)
Baseline Sitting Diastolic Blood Pressure (DBP)	92.2 (8.12)	92.2 (6.84)	92.2 (7.50)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Mean Sitting Cuff Blood Pressure <140/90 mmHg at the End of 6 Weeks of Treatment
Description	Sitting cuff blood pressure was calculated as the mean of three measurements taken approximately 2 minutes apart, and before the morning dose.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

Intent to Treat Efficacy (ITTE) Population: all randomized participants with efficacy (vital signs) data after a minimum of 4 weeks of treatment

Arm/Group Title	Lisinopril	Carvedilol CR + Lisinopril
Arm/Group Description	Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Measure Participants	203	201
Responders (mean BP <140/90 mmHg)	139 64.4%	137 63.4%
Non-responders (SBP >/=140 mmHg or DBP >/=90 mmHg)	64 29.6%	64 29.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lisinopril, Carvedilol CR + Lisinopril
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8822
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.968
	Confidence Interval	() 95%; 0.63 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6
Description	Mean change was calculated as Week 6 values minus Baseline values.
Time Frame	Baseline and Week 6

Outcome Measure Data

Analysis Population Description

ITTE

Arm/Group Title	Lisinopril	Carvedilol CR + Lisinopril
Arm/Group Description	Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Measure Participants	203	201
sSBP (mmHg)	-17.05 (12.27)	-16.07 (13.49)
sDBP (mmHg)	-10.15 (7.52)	-9.14 (9.65)

Adverse Events

Adverse Event Reporting Description	The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Arm/Group Title	Lisinopril		Carvedilol CR + Lisinopril
Arm/Group Description	Lisinopril monotherapy (10, 20, or 40 mg once daily)		Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
All Cause Mortality
	Lisinopril		Carvedilol CR + Lisinopril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lisinopril		Carvedilol CR + Lisinopril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/ (NaN)		3/ (NaN)
Cardiac disorders
Cardiac failure	1/216 (0.5%)		0/216 (0%)
Gastrointestinal disorders
Gastroesophageal reflux disease	0/216 (0%)		1/216 (0.5%)
General disorders
Non-cardiac chest pain	0/216 (0%)		1/216 (0.5%)
Infections and infestations
Meningitis viral	0/216 (0%)		1/216 (0.5%)
Injury, poisoning and procedural complications
Overdose	1/216 (0.5%)		0/216 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/216 (0%)		1/216 (0.5%)
Nervous system disorders
Headache	0/216 (0%)		1/216 (0.5%)
Psychiatric disorders
Suicide attempt	1/216 (0.5%)		0/216 (0%)
Other (Not Including Serious) Adverse Events
	Lisinopril		Carvedilol CR + Lisinopril
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/ (NaN)		54/ (NaN)
Gastrointestinal disorders
Nausea	6/216 (2.8%)		5/216 (2.3%)
Diarrhea	3/216 (1.4%)		7/216 (3.2%)
Dyspepsia	0/216 (0%)		3/216 (1.4%)
General disorders
Fatigue	11/216 (5.1%)		15/216 (6.9%)
Oedema peripheral	3/216 (1.4%)		1/216 (0.5%)
Infections and infestations
Gastroenteritis	3/216 (1.4%)		3/216 (1.4%)
Upper respiratory tract infection	3/216 (1.4%)		3/216 (1.4%)
Bronchitis	1/216 (0.5%)		3/216 (1.4%)
Sinusitis	0/216 (0%)		4/216 (1.9%)
Urinary tract infection	4/216 (1.9%)		0/216 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/216 (1.9%)		2/216 (0.9%)
Nervous system disorders
Headache	11/216 (5.1%)		10/216 (4.6%)
Dizziness	9/216 (4.2%)		9/216 (4.2%)
Respiratory, thoracic and mediastinal disorders
Cough	13/216 (6%)		11/216 (5.1%)
Skin and subcutaneous tissue disorders
Hyperhydrosis	1/216 (0.5%)		3/216 (1.4%)
Rash	3/216 (1.4%)		0/216 (0%)
Vascular disorders
Flushing	3/216 (1.4%)		2/216 (0.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.