Essential Hypertension
Conditions
Keywords
Moderate-to-Severe Hypertension, Essential Hypertension, Combination Therapy, Fixed-Combination Dose
Brief summary
The study will evaluate the blood pressure lowering effects of two different dosages of the combination of olmesartan and hydrochlorothiazide in patients with moderate or severe high blood pressure.
Interventions
DRUGolmesartan medoxomil (OM)+ hydrochlorothiazide (HCTZ) tablets
olmesartan medoxomil (OM)+ hydrochlorothiazide (HCTZ)tablets 40mg/25mg + 20mg/25mg matching placebo tablets once daily for 8 weeks
DRUGolmesartan medoxomil (OM)/ hydrochlorothiazide (HCTZ) 20mg/25mg
olmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ)20mg/25mg tablet + 40mg/25mg matching placebo tablet once a day for 8 weeks
Sponsors
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female Europeans aged 18 years or older with moderate to severe HTN, defined as follows (conventional BP measurements)
Exclusion criteria
* Female patients of childbearing potential pregnant, lactating or planning to become pregnant during the trial period. * Patients with serious disorders which may limit the ability to evaluate the efficacy or safety of the study medication, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological or oncological, neurological and psychiatric diseases. * Patients having a history of the following within the last six months: * myocardial infarction, * unstable angina pectoris, * percutaneous coronary intervention, * severe heart failure, * hypertensive encephalopathy, cerebrovascular accident (stroke) or * transient ischaemic attack. * Patients with clinically significant abnormal laboratory values at screening. * Patients with secondary HTN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Trough Sitting Diastolic Blood Pressure | 8 weeks | Change in mean trough sitting diastolic Blood Pressure between OM/HCTZ 20/25 mg vs. 40/25 mg, in those patients inadequately controlled on OM 40 mg monotherapy, after eight weeks of double blind treatment, as compared to baseline. Change = Week 16 - Week 8 (baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | 8 weeks | Change = Week 16 - Week 8 (baseline). |
| Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12 | 4 weeks | Change = Week 12 - Week 8 (baseline). |
| Change in Sitting Systolic Blood Pressure 4 Weeks and 8 Weeks After Baseline. | 8 weeks | 4 weeks Change = Week 12 - Week 8 (baseline). 8 weeks Change = Week 16 - Week 8 (baseline). |
| Number of Participants Achieving Blood Pressure Goal. | 8 weeks | — |
Countries
Belgium, Germany, Netherlands, Slovakia
Participant flow
Recruitment details
92 principal investigators screened patients at clinical sites in Europe (8 in Belgium, 17 in Germany, 12 in the Netherlands, 17 in Poland, 19 in Russia, 10 in Slovakia, and 9 in the Ukraine).Sites were either hospitals or general practitioners. First patient in: 05 December 2006 Last patient out: 07 May 2008
Pre-assignment details
Trial is 2 week taper-off phase and 2 treatment periods. Period I - 8-week open-label OM 40mg. Only non-responders eligible to randomise into Period II. Period II - 8-week double-blind patients assigned into one of two arms. Results provided for Period II only.
Participants by arm
| Arm | Count |
|---|---|
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo Olmesartan Medoxomil/Hydrochlorothiazide 40/25 mg with 20/25 mg matching placebo | 502 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo Olmesartan Medoxomil/Hydrochlorothiazide 20/25mg + 40/25mg matching placebo | 508 |
| Total | 1,010 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 6 |
| Overall Study | concomitant medication,etc. | 5 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 9.77 | 54.7 years STANDARD_DEVIATION 9.67 | 54.6 years STANDARD_DEVIATION 9.72 |
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Customized >=65 years | 75 Participants | 93 Participants | 168.0 Participants |
| Age, Customized >= 75 years | 11 Participants 2.2 | 5 Participants 1 | 16.0 Participants |
| Age, Customized Between 18 and 65 years | 422 Participants | 404 Participants | 826.0 Participants |
| Race/Ethnicity, Customized European | 508 participants | 502 participants | 1010 participants |
| Sex: Female, Male Female | 201 Participants | 194 Participants | 395 Participants |
| Sex: Female, Male Male | 307 Participants | 308 Participants | 615 Participants |
Outcome results
Primary
Change in Mean Trough Sitting Diastolic Blood Pressure
Change in mean trough sitting diastolic Blood Pressure between OM/HCTZ 20/25 mg vs. 40/25 mg, in those patients inadequately controlled on OM 40 mg monotherapy, after eight weeks of double blind treatment, as compared to baseline. Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks
Population: The main analysis will be performed on the full analysis set last observation carried forward (LOCF). Pooling will be applied for small centres.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure | -11.16 mm Hg | Standard Deviation 8.851 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure | -10.45 mm Hg | Standard Deviation 7.928 |
Comparison: The ANCOVA model included treatment as main effect and baseline mean trough sitting dBP as covariate.~Significance level alpha = 5%. Power = 80%.~The following statistical superiority hypothesis was tested:~Superiority of OM/HCTZ combination therapy 40/25 mg over OM/HCTZ 20/25 mgp-value: 0.264895% CI: [-1.51, 0.42]ANCOVA
Secondary
Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline.
Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks
Population: Exploratory analysis: ANCOVA was used to compare the differences in change from baseline (Visit 4, Week 8) to Week 16 (Visit 6) in daytime, nighttime and 24-hr ABPM dBP and sBP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in daytime ABPM dBP | -9.3 mm Hg | Standard Deviation 9.18 |
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in mean 24-hr ABPM sBP | -14.7 mm Hg | Standard Deviation 13.75 |
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in daytime ABPM sBP | -15.0 mm Hg | Standard Deviation 14.36 |
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to Wk 16 in mean 24-hr ABPM dBP | -9.2 mm Hg | Standard Deviation 8.69 |
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in nighttime ABPM sBP | -13.4 mm Hg | Standard Deviation 14.59 |
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in nighttime ABPM dBP | -8.6 mm Hg | Standard Deviation 9.52 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in nighttime ABPM sBP | -10.7 mm Hg | Standard Deviation 13.16 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to Wk 16 in mean 24-hr ABPM dBP | -7.6 mm Hg | Standard Deviation 8.03 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in daytime ABPM dBP | -7.7 mm Hg | Standard Deviation 8.48 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in nighttime ABPM dBP | -7.0 mm Hg | Standard Deviation 9.49 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in daytime ABPM sBP | -12.3 mm Hg | Standard Deviation 12.45 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Daytime, Nighttime and 24-hour Blood Pressure Evaluated by Ambulatory Blood Pressure Monitoring 8 Weeks After Baseline. | Change from Week 8 to wk16 in mean 24-hr ABPM sBP | -12.0 mm Hg | Standard Deviation 11.81 |
p-value: 0.001695% CI: [-2.58, -0.6]ANCOVA
p-value: 0.003195% CI: [-2.61, -0.53]ANCOVA
p-value: 0.007395% CI: [-2.58, -0.4]ANCOVA
p-value: 0.002195% CI: [-3.71, -0.82]ANCOVA
p-value: 0.003195% CI: [-3.76, -0.76]ANCOVA
p-value: 0.010495% CI: [-3.61, -0.48]ANCOVA
Secondary
Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12
Change = Week 12 - Week 8 (baseline).
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12 | -9.32 mm Hg | Standard Deviation 7.82 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12 | -8.83 mm Hg | Standard Deviation 7.584 |
p-value: 0.424695% CI: [-1.26, 0.53]ANCOVA
Secondary
Change in Sitting Systolic Blood Pressure 4 Weeks and 8 Weeks After Baseline.
4 weeks Change = Week 12 - Week 8 (baseline). 8 weeks Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Sitting Systolic Blood Pressure 4 Weeks and 8 Weeks After Baseline. | Change from baseline (Week 8) to Week 16 in sBP | -17.41 mm Hg | Standard Deviation 13.93 |
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Change in Sitting Systolic Blood Pressure 4 Weeks and 8 Weeks After Baseline. | Change from baseline (Week 8) to Week 12 in sBP | -14.07 mm Hg | Standard Deviation 12.654 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Sitting Systolic Blood Pressure 4 Weeks and 8 Weeks After Baseline. | Change from baseline (Week 8) to Week 16 in sBP | -17.09 mm Hg | Standard Deviation 13.126 |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Change in Sitting Systolic Blood Pressure 4 Weeks and 8 Weeks After Baseline. | Change from baseline (Week 8) to Week 12 in sBP | -13.80 mm Hg | Standard Deviation 12.519 |
p-value: 0.701995% CI: [-1.84, 1.24]ANCOVA
p-value: 0.732895% CI: [-1.71, 1.21]ANCOVA
Secondary
Number of Participants Achieving Blood Pressure Goal.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OM/HCTZ 40/25 mg + 20/25 mg Matching Placebo | Number of Participants Achieving Blood Pressure Goal. | 260 participants |
| OM/HCTZ 20/25 mg + 40/25 mg Matching Placebo | Number of Participants Achieving Blood Pressure Goal. | 255 participants |
95% CI: [0.85, 1.4]Regression, Logistic