Trial Outcomes & Findings for Research Study To Test Carvedilol CR + Lisinopril Versus Lisinopril + Placebo In Patients With High Blood Pressure (NCT NCT00624065)

Last Updated: 2016-12-28

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

348 participants

Primary outcome timeframe

Week 6

Results posted on

2016-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	Lisinopril Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Overall Study STARTED	216	216
Overall Study COMPLETED	197	192
Overall Study NOT COMPLETED	19	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Lisinopril Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Overall Study Adverse Event	5	6
Overall Study Lost to Follow-up	4	1
Overall Study Consent withdrawn	6	5
Overall Study Lack of Efficacy	0	3
Overall Study Met protocol-defined stopping criteria	4	9

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lisinopril n=216 Participants Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril n=216 Participants Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)	Total n=432 Participants Total of all reporting groups
Age, Continuous	54.0 years STANDARD_DEVIATION 11.9 • n=5 Participants	54.1 years STANDARD_DEVIATION 9.8 • n=7 Participants	54.1 years STANDARD_DEVIATION 10.9 • n=5 Participants
Gender Female	95 Participants n=5 Participants	95 Participants n=7 Participants	190 Participants n=5 Participants
Gender Male	121 Participants n=5 Participants	121 Participants n=7 Participants	242 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage (AA/AH)	45 Participants n=5 Participants	29 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Japanese/East Asian/South East Asian Heritage	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Asian Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	150 Participants n=5 Participants	178 Participants n=7 Participants	328 Participants n=5 Participants
Race/Ethnicity, Customized AA/AH & American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized AA/AH & American Indian or Alaska Native & White	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized AA/AH & White	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Baseline Blood Pressure Baseline Sitting Systolic Blood Pressure (SBP)	149.8 mm/Hg STANDARD_DEVIATION 10.25 • n=5 Participants	148.8 mm/Hg STANDARD_DEVIATION 10.30 • n=7 Participants	149.3 mm/Hg STANDARD_DEVIATION 10.27 • n=5 Participants
Baseline Blood Pressure Baseline Sitting Diastolic Blood Pressure (DBP)	92.2 mm/Hg STANDARD_DEVIATION 8.12 • n=5 Participants	92.2 mm/Hg STANDARD_DEVIATION 6.84 • n=7 Participants	92.2 mm/Hg STANDARD_DEVIATION 7.50 • n=5 Participants

PRIMARY outcome

Timeframe: Week 6

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

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

Outcome measures

Outcome measures
Measure	Lisinopril n=203 Participants Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril n=201 Participants Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Number of Participants With Mean Sitting Cuff Blood Pressure <140/90 mmHg at the End of 6 Weeks of Treatment Responders (mean BP <140/90 mmHg)	139 Participants	137 Participants
Number of Participants With Mean Sitting Cuff Blood Pressure <140/90 mmHg at the End of 6 Weeks of Treatment Non-responders (SBP >/=140 mmHg or DBP >/=90 mmHg)	64 Participants	64 Participants

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: ITTE

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

Outcome measures

Outcome measures
Measure	Lisinopril n=203 Participants Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril n=201 Participants Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6 sSBP (mmHg)	-17.05 mmHg Standard Deviation 12.27	-16.07 mmHg Standard Deviation 13.49
Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6 sDBP (mmHg)	-10.15 mmHg Standard Deviation 7.52	-9.14 mmHg Standard Deviation 9.65

Adverse Events

Lisinopril

Serious events: 2 serious events

Other events: 50 other events

Deaths: 0 deaths

Carvedilol CR + Lisinopril

Serious events: 3 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lisinopril Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Cardiac disorders Cardiac failure	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
General disorders Non-cardiac chest pain	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Infections and infestations Meningitis viral	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Injury, poisoning and procedural complications Overdose	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Nervous system disorders Headache	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Psychiatric disorders Suicide attempt	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Lisinopril Lisinopril monotherapy (10, 20, or 40 mg once daily)	Carvedilol CR + Lisinopril Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily)
Nervous system disorders Headache	5.1% 11/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	4.6% 10/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
General disorders Fatigue	5.1% 11/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	6.9% 15/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Respiratory, thoracic and mediastinal disorders Cough	6.0% 13/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	5.1% 11/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Nervous system disorders Dizziness	4.2% 9/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	4.2% 9/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Gastrointestinal disorders Nausea	2.8% 6/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	2.3% 5/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Gastrointestinal disorders Diarrhea	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	3.2% 7/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 4/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.93% 2/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Infections and infestations Gastroenteritis	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Infections and infestations Upper respiratory tract infection	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Vascular disorders Flushing	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.93% 2/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Infections and infestations Bronchitis	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Skin and subcutaneous tissue disorders Hyperhydrosis	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
General disorders Oedema peripheral	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.46% 1/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Infections and infestations Sinusitis	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	1.9% 4/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Infections and infestations Urinary tract infection	1.9% 4/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Gastrointestinal disorders Dyspepsia	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.
Skin and subcutaneous tissue disorders Rash	1.4% 3/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.	0.00% 0/216 The frequency threshold for reporting Other Adverse Events is 1% in either treatment group.