Hypertension
Conditions
Keywords
target blood pressure, hypertension, COREG CR, carvedilol CR, Stage 1 or 2 essential hypertension, lisinopril
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.
Interventions
DRUGcarvedilol controlled release/lisinopril
carvedilol CR + lisinopril given as separate pills
DRUGlisinopril + placebo
lisinopril plus placebo to match carvedilol CR
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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 Subjects taking one hypertensive medication had their medication withdrawn and entered a wash-out phase prior to randomization.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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lisinopril Lisinopril monotherapy (10, 20, or 40 mg once daily) | 216 |
| Carvedilol CR + Lisinopril Carvedilol controlled release (CR) + lisinopril (20 + 10, 20 + 20, or 40 + 20 mg once daily) | 216 |
| Total | 432 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Consent withdrawn | 6 | 5 |
| Overall Study | Lack of Efficacy | 0 | 3 |
| Overall Study | Lost to Follow-up | 4 | 1 |
| Overall Study | Met protocol-defined stopping criteria | 4 | 9 |
Baseline characteristics
| Characteristic | Lisinopril | Carvedilol CR + Lisinopril | Total |
|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 11.9 | 54.1 years STANDARD_DEVIATION 9.8 | 54.1 years STANDARD_DEVIATION 10.9 |
| Baseline Blood Pressure Baseline Sitting Diastolic Blood Pressure (DBP) | 92.2 mm/Hg STANDARD_DEVIATION 8.12 | 92.2 mm/Hg STANDARD_DEVIATION 6.84 | 92.2 mm/Hg STANDARD_DEVIATION 7.5 |
| Baseline Blood Pressure Baseline Sitting Systolic Blood Pressure (SBP) | 149.8 mm/Hg STANDARD_DEVIATION 10.25 | 148.8 mm/Hg STANDARD_DEVIATION 10.3 | 149.3 mm/Hg STANDARD_DEVIATION 10.27 |
| Gender Female | 95 Participants | 95 Participants | 190 Participants |
| Gender Male | 121 Participants | 121 Participants | 242 Participants |
| Race/Ethnicity, Customized AA/AH & American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized AA/AH & American Indian or Alaska Native & White | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized AA/AH & White | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized African American/African Heritage (AA/AH) | 45 Participants | 29 Participants | 74 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Japanese/East Asian/South East Asian Heritage | 16 Participants | 6 Participants | 22 Participants |
| Race/Ethnicity, Customized Mixed Asian Heritage | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 150 Participants | 178 Participants | 328 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / — | 54 / — |
| serious Total, serious adverse events | 2 / — | 3 / — |
Outcome results
Primary
Number of Participants With Mean Sitting Cuff Blood Pressure <140/90 mmHg at the End of 6 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.
Time frame: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lisinopril | 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 |
| Lisinopril | 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 |
| Carvedilol CR + Lisinopril | 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) | 137 Participants |
| Carvedilol CR + Lisinopril | 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 |
p-value: 0.882295% CI: [0.63, 1.49]Regression, Logistic
Secondary
Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6
Mean change was calculated as Week 6 values minus Baseline values.
Time frame: Baseline and Week 6
Population: ITTE
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lisinopril | 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 |
| Lisinopril | 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 |
| Carvedilol CR + Lisinopril | Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6 | sSBP (mmHg) | -16.07 mmHg | Standard Deviation 13.49 |
| Carvedilol CR + Lisinopril | Mean Change From Baseline in Sitting Systolic Blood Pressure (sSBP) and Sitting Diastolic Blood Pressure (sDBP) at Week 6 | sDBP (mmHg) | -9.14 mmHg | Standard Deviation 9.65 |