Hypertension
Conditions
Brief summary
This is a multi-centre, randomised, double-blind, active-controlled, parallel-group comparative trial to compare the fixed dose combination (FDC) of telmisartan 80 mg +hydrochlorothiazide 12.5 mg and amlodipine 5 mg (T80/A5/H12.5 mg) to telmisartan 80 mg+ amlodipine 5 mg (T80/A5 mg) in blood pressure lowering effect at week 8, the end of the double-blind period in essential hypertensive patients who fail to respond adequately to telmisartan 80 mg+ amlodipine 5 mg. Patients are assigned to one of the two groups after a 6-week open-label run-in period taking T80/A5 mg.
Interventions
FDC tablet
DRUGhydrochlorothiazide
tablet
DRUGPlacebo
placebo matching hydrochlorothiazide tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
20 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Essential hypertensive patients who have already taking 2 or 3 antihypertensive drugs and mean seated diastolic blood pressure (DBP) must be \>=90 and \<=114 mmHg and mean seated systolic blood pressure (SBP) must be =\<200 mmHg * Able to stop all current antihypertensive drugs (other than study medication) from Visit 1b through the end of the trial without risk to the patient based on the investigator's opinion * Age 20 years or older
Exclusion criteria
* Patients with known or suspected secondary hypertension * Patients with clinically relevant cardiac arrhythmia * Congestive heart failure with New York Heart Association (NYHA) functional class III-IV * Patients with recent cardiovascular events * Patients with recent stroke events * Patients with a history of sudden deterioration of renal function with angiotensin II receptor blockers or angiotensin converting enzyme inhibitors; or patients with post-renal transplant or post-nephrectomy * Patients with hepatic and/or renal dysfunction * Pre-menopausal women who are nursing or pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | baseline and week 8 | Change from baseline in mean seated diastolic blood pressure (DBP) at trough after 8 weeks of the double-blind period. After patients had rested in a seated position for approximately 5 minutes, blood pressure was measured 3 times at approximately 2-minute intervals. The mean of the 3 measurements are used as endpoints. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | baseline and week 8 | Change from baseline in mean seated systolic blood pressure (SBP) at trough after 8 weeks of the double-blind period. After patients had rested in a seated position for approximately 5 minutes, blood pressure was measured 3 times at approximately 2-minute intervals. The mean of the 3 measurements are used as endpoints. |
| The Proportion of Patients With DBP<90 mmHg and SBP<140 mmHg as Seated Blood Pressure at Trough After 8 Weeks of the Double-blind Period | baseline and week 8 | Patients with trough seated DBP =\>90 mmHg or trough seated SBP \>=140 mmHg at baseline were analysed. |
Countries
Japan
Participant flow
Pre-assignment details
This study is randomised, double-blind, active-control, parallel-group comparison
Participants by arm
| Arm | Count |
|---|---|
| Telmisartan and Amlodipine+HCTZ Subjects who were orally administered once daily with fixed dose combination (FDC) tablet of telmisartan 80 mg and amlodipine 5 mg+ hydrochlorothiazide (HCTZ) 12.5 mg tablet. | 149 |
| Telmisartan+Amlodipine Subjects who were orally administered once daily with the fixed-dose combination tablet of telmisartan 80 mg and amlodipine 5 mg + placebo matching to hydrochlorothiazide 12.5 mg tablet | 160 |
| Total | 309 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Other than stated | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Telmisartan and Amlodipine+HCTZ | Telmisartan+Amlodipine | Total |
|---|---|---|---|
| Age, Continuous | 54.4 Years STANDARD_DEVIATION 9.1 | 55.0 Years STANDARD_DEVIATION 9.7 | 54.7 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 22 Participants | 30 Participants | 52 Participants |
| Sex: Female, Male Male | 127 Participants | 130 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 149 | 14 / 160 |
| serious Total, serious adverse events | 0 / 149 | 0 / 160 |
Outcome results
Primary
Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period.
Change from baseline in mean seated diastolic blood pressure (DBP) at trough after 8 weeks of the double-blind period. After patients had rested in a seated position for approximately 5 minutes, blood pressure was measured 3 times at approximately 2-minute intervals. The mean of the 3 measurements are used as endpoints.
Time frame: baseline and week 8
Population: Full analysis set (FAS): This analysis set was, conforming to the intent-to-treat principle, defined as all patients i) included in the treated set; and ii) taking measurements of seated DBP at reference baseline and at 1 or more time points during the double-blind period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan and Amlodipine+HCTZ | Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | -8.4 mmHg | Standard Error 0.5 |
| Telmisartan+Amlodipine | Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | -4.5 mmHg | Standard Error 0.5 |
Comparison: The last observation carried forward (LOCF) method was applied for missing data, where the value from the measurements at the closest preceding visit replaced the missing value.p-value: <0.000195% CI: [-5.3, -2.4]ANCOVA
Secondary
Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period.
Change from baseline in mean seated systolic blood pressure (SBP) at trough after 8 weeks of the double-blind period. After patients had rested in a seated position for approximately 5 minutes, blood pressure was measured 3 times at approximately 2-minute intervals. The mean of the 3 measurements are used as endpoints.
Time frame: baseline and week 8
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telmisartan and Amlodipine+HCTZ | Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | -12.3 mmHg | Standard Error 0.8 |
| Telmisartan+Amlodipine | Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | -6.9 mmHg | Standard Error 0.8 |
Comparison: The last observation carried forward (LOCF) method was applied for missing data, where the value from the measurements at the closest preceding visit replaced the missing value.p-value: <0.000195% CI: [-7.6, -3.1]ANCOVA
Secondary
The Proportion of Patients With DBP<90 mmHg and SBP<140 mmHg as Seated Blood Pressure at Trough After 8 Weeks of the Double-blind Period
Patients with trough seated DBP =\>90 mmHg or trough seated SBP \>=140 mmHg at baseline were analysed.
Time frame: baseline and week 8
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telmisartan and Amlodipine+HCTZ | The Proportion of Patients With DBP<90 mmHg and SBP<140 mmHg as Seated Blood Pressure at Trough After 8 Weeks of the Double-blind Period | 51.7 percentage of participants |
| Telmisartan+Amlodipine | The Proportion of Patients With DBP<90 mmHg and SBP<140 mmHg as Seated Blood Pressure at Trough After 8 Weeks of the Double-blind Period | 36.9 percentage of participants |
Comparison: The Non-completers considered failure (NCF) method was applied for missing data, where missing data due to early discontinuation will be replaced as failure up to the planned final visit to be reached by all patients.p-value: <0.005195% CI: [1.2, 3.4]Regression, Logistic