Hypertension
Conditions
Keywords
Hypertension, Angiotensin Receptor Blocker, Calcium Channel Blocker, Angiotensin Converting Enzyme Inhibitor, Hydrochlorothiazide, Stage I and II Hypertension
Brief summary
This 14 week study will examine the ability of olmesartan medoxomil to lower the blood pressure of patients 65 years of age or older with high blood pressure. The medication being tested has been approved by the FDA for the treatment of high blood pressure.
Interventions
DRUGOlmesartan medoxomil
Tablets
Tablets
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males or Females greater than 65 years of age 2. Patients with a mean seated systolic blood pressure (MSSBP) greater than or equal to 150 mmHg but less than 200 mm Hg and a mean seated diastolic blood pressure (MSDBP) less than or equal to 109 mmHg following a 2-3 week single blind placebo run-in period. 3. The difference in MSSBP between visits 2 and 3 or between visits 3 and 3x must be less than or equal to 10 mmHg. 4. Patients with a mean daytime (8am-4pm) systolic blood pressure (SBP) greater than or equal to 140 mmHg and less than or equal to 199 mmHg and a mean daytime diastolic blood pressure (DBP) less than or equal to 109 mmHg as measured by an ambulatory blood pressure monitoring device (ABPM) following placebo run-in period.
Exclusion criteria
1. History of stroke or transient ischemic attack (TIA) within the last one year. 2. History of myocardial infarction, angina, coronary angioplasty, coronary artery bypass graft, or heart failure within the past 6 months. 3. Severe hypertension (diastolic blood pressure greater than 115 mmHg or systolic blood pressure greater than or equal to 200 mmHg). 4. Patients with secondary hypertension of any etiology, such as renal disease, pheochromocytoma or Cushing's syndrome. 5. Type I diabetes or Type II diabetics not on stable treatment for greater than or equal to 4 weeks and plasma glucose greater than 160 mg/dl. 6. Evidence of symptomatic resting bradycardia, congestive heart failure, or hemodynamically significant cardiac valvular disease. 7. Presence of heart block greater than first degree sinoatrial block, Wolff-Parkinson-White Syndrome, Sick Sinus Syndrome, an accessory bypass tract, atrial fibrillation, atrial flutter or any arrhythmia requiring medication. 8. Serum Creatinine greater than 1.7 mg/dl, or other abnormal laboratory values deemed clinically significant by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure After 12 Weeks of Active Treatment. | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
| Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10pm-6am)Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
| Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10 Pm-6am) Ambulatory Blood Pressure Monitored Diastolic Blood Pressure After 12 Weeks of Active Treatment | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
| Number of Subjects Who Achieved Mean 24-hour Ambluatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
| Number of Subjects Who Achieved Mean Daytime (8am - 4pm) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
| Number of Subjects Who Achieved Mean Nighttime (10pm - 6am) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | baseline to 12 weeks | All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 37 US sites (private medical practices and small clinics) over 13 months (Nov 29,06 to Dec 28,07) from each physician's clientele base. Approximately 200 eligible participants, men and women at least 65 years of age with hypertension or uncontrolled hypertension on current medication, were to receive active treatment
Pre-assignment details
After 3-4 weeks of placebo, patients with a systolic pressure (SBP) ≥150 ≤199mmHg and diastolic pressure (DBP) ≤109 mmHg at the last 2 visits, and 8-hr daytime SBP \>140 and ≤199 mmHg and DBP ≤109 mmHg by ambulatory blood pressure monitoring were entered.All started with Olmesartan 20 mg and were titrated if their blood pressure was not controlled
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment Period All participants started the active treatment period with 20 mg olmesartan medoxomil (Olm). After 3 weeks participants were titrated to 40 mg Olm, if their blood pressure was not controlled. After 6 weeks they were titrated to the next step which now included Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg if their blood pressure was not controlled. After 9 weeks they were titrated to the next step which now included Olm 40 mg + HCTZ 25 mg if their blood pressure was not controlled. | 178 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Olmesartan 40 mg | Adverse Event | 4 |
| Olmesartan 40 mg | Lack of Efficacy | 3 |
| Olmesartan 40 mg | Withdrawal by Subject | 1 |
| Olmesartan (Olm) 20 mg | Adverse Event | 1 |
| Olmesartan (Olm) 20 mg | Lack of Efficacy | 2 |
| Olmesartan (Olm) 20 mg | Other | 1 |
| Olmesartan (Olm) 20 mg | Protocol Violation | 1 |
| Olmesartan (Olm) 20 mg | Withdrawal by Subject | 2 |
| Olm+Hydrochlorothiazide 12.5 mg | Adverse Event | 3 |
| Olm+Hydrochlorothiazide 12.5 mg | Withdrawal by Subject | 3 |
| Olm+ Hydrochlorothiazide 25 mg | Adverse Event | 1 |
| Olm+ Hydrochlorothiazide 25 mg | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Active Treatment Period |
|---|---|
| Age Continuous | 72.0 years STANDARD_DEVIATION 5.3 |
| Baseline 24-hour ambulatory diastolic blood pressure | 80.7 mm Hg STANDARD_DEVIATION 8.5 |
| Baseline 24-hour ambulatory systolic blood pressure | 149.1 mm Hg STANDARD_DEVIATION 11.2 |
| Baseline diastolic blood pressure | 87.7 mm Hg STANDARD_DEVIATION 9.6 |
| Baseline heart rate | 71.5 beats/minute STANDARD_DEVIATION 11.4 |
| Baseline stage of hypertension Stage 1 hypertension | 62 participants |
| Baseline stage of hypertension Stage 2 hypertension | 116 participants |
| Baseline systolic blood pressure | 165.5 mm Hg STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 178 participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 93 Participants |
Outcome results
Primary
Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had a baseline and week 12 ABPM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Change From Baseline in Mean 24-hour Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment | -25.7 mm Hg | Standard Error 0.96 |
Comparison: The sample size of this study was not based on the statistical power consideration and was considered as sufficient for the evaluation of the efficacy and safety of the proposed olmesartan medoxomil-based treatment regimen.p-value: <0.0001one-sample t-test
Secondary
Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure After 12 Weeks of Active Treatment.
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had a baseline and week 12 ABPM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study | Change From Baseline in Mean 24-hour Ambulatory Diastolic Blood Pressure After 12 Weeks of Active Treatment. | -12.3 mm Hg | Standard Error 0.55 |
p-value: <0.0001One-sample t-test
Secondary
Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10 Pm-6am) Ambulatory Blood Pressure Monitored Diastolic Blood Pressure After 12 Weeks of Active Treatment
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had baseline and week 12 ABPM measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10 Pm-6am) Ambulatory Blood Pressure Monitored Diastolic Blood Pressure After 12 Weeks of Active Treatment | Daytime | -13.0 mm Hg | Standard Error 0.65 |
| Overall Study | Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10 Pm-6am) Ambulatory Blood Pressure Monitored Diastolic Blood Pressure After 12 Weeks of Active Treatment | Nighttime | -11.5 mm Hg | Standard Error 0.6 |
p-value: <0.0001one-sample t-test
Secondary
Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10pm-6am)Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had a baseline and week 12 ABPM.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10pm-6am)Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment | Daytime | -26.5 mm Hg | Standard Error 1.1 |
| Overall Study | Change From Baseline in Mean Daytime (8am-4pm) and Mean Nighttime (10pm-6am)Ambulatory Systolic Blood Pressure After 12 Weeks of Active Treatment | Nighttime | -24.4 mm Hg | Standard Error 1.04 |
p-value: <0.0001one-sample t-test
Secondary
Number of Subjects Who Achieved Mean 24-hour Ambluatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had a baseline and week 12 ABPM.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Number of Subjects Who Achieved Mean 24-hour Ambluatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment | BP<140/90 mm Hg | 133 participants |
| Overall Study | Number of Subjects Who Achieved Mean 24-hour Ambluatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment | SBP<140 mm Hg | 133 participants |
| Overall Study | Number of Subjects Who Achieved Mean 24-hour Ambluatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment | DBP<90 mm Hg | 149 participants |
Secondary
Number of Subjects Who Achieved Mean Daytime (8am - 4pm) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment.
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had a baseline and week 12 ABPM.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Number of Subjects Who Achieved Mean Daytime (8am - 4pm) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | BP<140/90 mm Hg | 120 participants |
| Overall Study | Number of Subjects Who Achieved Mean Daytime (8am - 4pm) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | SBP<140 mm Hg | 120 participants |
| Overall Study | Number of Subjects Who Achieved Mean Daytime (8am - 4pm) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | DBP<90 mm Hg | 145 participants |
Secondary
Number of Subjects Who Achieved Mean Nighttime (10pm - 6am) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment.
All participants started the treatment arm with 20 mg olmesartan medoxomil (Olm). If their blood pressure was not controlled, participants were titrated at 3-week intervals to: Olm 40 mg, then, if needed Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg, then, if needed Olm 40 mg + HCTZ 25 mg This outcome measure included all participants at the end of the 12-week treatment period regardless of whether or not they were titrated. They had to have both baseline and 12-week ambulatory blood pressure measurements.
Time frame: baseline to 12 weeks
Population: 178 participants started the active treatment period. 23 dropped out. 150=The ambulatory blood pressure monitoring (ABPM) subset was defined as subjects who received at least one dose of active study medication and had a baseline and week 12 ABPM.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Number of Subjects Who Achieved Mean Nighttime (10pm - 6am) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | BP<140/90 mm Hg | 143 participants |
| Overall Study | Number of Subjects Who Achieved Mean Nighttime (10pm - 6am) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | SBP<140 mm Hg | 143 participants |
| Overall Study | Number of Subjects Who Achieved Mean Nighttime (10pm - 6am) Ambulatory Blood Pressure of <140/90 mm Hg, Systolic Blood Pressure <140 mm Hg, and Diastolic Blood Pressure <90 mm Hg After 12 Weeks of Active Treatment. | DBP<90 mm Hg | 149 participants |