Hypertension
Conditions
Brief summary
The primary objective of this trial is to demonstrate that the fixed dose combination of telmisartan 40mg + amlodipine 10mg (T40/A10) or the fixed dose combination of telmisartan 80mg + amlodipine 10mg (T80/A10) is superior in reducing blood pressure at eight weeks compared with amlodipine 10mg monotherapy (A10) in patients who fail to respond to six weeks treatment with A10.
Interventions
DRUGamlodipine
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* diagnosis of essential hypertension and blood pressure not adequately controlled before informed consent (inadequate control defined as seated diastolic blood pressure (DBP) \>= 95 mmHg if on existing antihypertensive treatment or seated DBP \>= 100 mmHg if treatment-naïve). * failure to respond to six weeks treatment with amlodipine 10mg. (Failure to respond defined as seated DBP \>= 90 mmHg.) * able to stop any current antihypertensive therapy without unacceptable risk to the patient. * willing and able to provide written informed consent.
Exclusion criteria
* pregnancy, breast-feeding, unwilling to use effective contraception (if female of child-bearing potential). * known or suspected secondary hypertension. * mean seated systolic blood pressure (SBP) \>=200 mmHg and/or mean seated DBP \>= 120 mmHg during run-in treatment or mean seated SBP \>= 180 mmHg and/or mean seated DBP \>= 120 mmHg at the randomisation visit or at any time during randomised treatment. * any clinically significant hepatic impairment or severe renal impairment bilateral renal artery stenosis or renal artery stenosis in a solitary kidney or post post-renal transplant. * clinically relevant hyperkalaemia. * uncorrected volume or sodium depletion. * primary aldosteronism. * hereditary fructose or lactose intolerance. * symptomatic congestive heart failure. * patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or ARBs. * history of drug or alcohol dependency within the six months prior to signing consent. * concurrent participation in another clinical trial or any investigational therapy within thirty days prior to signing consent. * hypertrophic obstructive cardiomyopathy, hemodynamically relevant stenosis of the aortic or mitral valve. * known allergic hypersensitivity to any component of the formulations under investigation. (Includes known hypersensitivity to telmisartan or other ARBs or amlodipine or other dihydropyridine CCBs.) * non-compliance with study medication (defined as less than 80% or more than 120%) during the open-label run-in treatment period. * current treatment with any antihypertensive agents, whether or not prescribed for this indication, that cannot be safely stopped (investigator¿s decision) by the start of the run-in period. * chronic administration of any medication known to affect blood pressure, other than the trial medication. * any other clinical condition which, in the opinion of the investigator, would not allow safe completion of the protocol and safe administration of telmisartan and amlodipine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Seated Diastolic Blood Pressure | Baseline and end of study (8 weeks or last value on treatment) | Change from baseline to the end of study in trough DBP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | End of study (8 weeks or last value on treatment) | The number of patients who reach the target DBP of \<90mmHg |
| Trough Seated Diastolic Blood Pressure <80 mmHg | End of study (8 weeks or last value on treatment) | The number of patients who reach the target DBP of \<80mmHg |
| Trough Seated DBP Response | End of study (8 weeks or last value on treatment) | The number of patients who reach the target DBP of \<90mmHg or had a reduction in DBP \>= 10mmHg |
| Trough Seated SBP Control | End of study (8 weeks or last value on treatment) | The number of patients who reach the target SBP of \<140mmHg |
| Change From Baseline in Trough Seated Systolic Blood Pressure | Baseline and end of study (8 weeks or last value on treatment) | Change from baseline to the end of study in trough SBP |
| Trough Seated BP Normality Classes | End of study (8 weeks or last value on treatment) | The number of patients who reach predefined BP categories |
| Oedema Incidence Rate | During randomised treatment period | The number of patients who experienced at least one case of oedema or worsening of oedema for the first time (expressed as number of patients/100 patient-years) |
| Peripheral Oedema Incidence Rate | During randomised treatment period | The number of cases of peripheral oedema (expressed as number of cases/100 patient-years) |
| Trough Seated SBP Response | End of study (8 weeks or last value on treatment) | The number of patients who reach the target SBP of \<140mmHg or had a reduction in SBP \>= 15 mmHg |
Countries
Australia, Austria, Bulgaria, Czechia, Ireland, Italy, New Zealand, Russia, Slovakia, Spain, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine 10mg | 315 |
| Telmisartan 40mg and Amlodipine 10mg | 315 |
| Telmisartan 80mg and Amlodipine 10mg | 317 |
| Total | 947 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 10 | 5 |
| Overall Study | Consent withdrawn | 2 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Non compliant with protocol | 3 | 3 | 2 |
| Overall Study | Specified category | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Amlodipine 10mg | Telmisartan 40mg and Amlodipine 10mg | Telmisartan 80mg and Amlodipine 10mg | Total |
|---|---|---|---|---|
| Age, Continuous | 56.4 Years STANDARD_DEVIATION 10.4 | 57.6 Years STANDARD_DEVIATION 9.4 | 55.5 Years STANDARD_DEVIATION 9.8 | 56.5 Years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 128 Participants | 145 Participants | 146 Participants | 419 Participants |
| Sex: Female, Male Male | 187 Participants | 170 Participants | 171 Participants | 528 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 22 / — | 21 / — | 27 / — |
| serious Total, serious adverse events | 1 / — | 3 / — | 0 / — |
Outcome results
Primary
Change From Baseline in Trough Seated Diastolic Blood Pressure
Change from baseline to the end of study in trough DBP
Time frame: Baseline and end of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 10mg | Change From Baseline in Trough Seated Diastolic Blood Pressure | -6.48 mmHg | Standard Error 0.45 |
| Telmisartan 40mg and Amlodipine 10mg | Change From Baseline in Trough Seated Diastolic Blood Pressure | -9.24 mmHg | Standard Error 0.45 |
| Telmisartan 80mg and Amlodipine 10mg | Change From Baseline in Trough Seated Diastolic Blood Pressure | -9.33 mmHg | Standard Error 0.45 |
Comparison: Testing that the combination treatments are superior to monotherapy A10.~The number of patients in the treatment arms ensure the tests have over 90% power.p-value: <0.000195% CI: [-3.77, -1.75]ANCOVA
Comparison: Testing that the combination treatments are superior to monotherapy A10.~The number of patients in the treatment arms ensure the tests have over 90% power.p-value: <0.000195% CI: [-3.86, -1.84]ANCOVA
Secondary
Change From Baseline in Trough Seated Systolic Blood Pressure
Change from baseline to the end of study in trough SBP
Time frame: Baseline and end of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 10mg | Change From Baseline in Trough Seated Systolic Blood Pressure | -7.44 mmHg | Standard Error 0.66 |
| Telmisartan 40mg and Amlodipine 10mg | Change From Baseline in Trough Seated Systolic Blood Pressure | -11.09 mmHg | Standard Error 0.66 |
| Telmisartan 80mg and Amlodipine 10mg | Change From Baseline in Trough Seated Systolic Blood Pressure | -11.29 mmHg | Standard Error 0.66 |
p-value: <0.000195% CI: [-5.15, -2.16]ANCOVA
p-value: <0.000195% CI: [-5.35, -2.36]ANCOVA
Secondary
Oedema Incidence Rate
The number of patients who experienced at least one case of oedema or worsening of oedema for the first time (expressed as number of patients/100 patient-years)
Time frame: During randomised treatment period
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amlodipine 10mg | Oedema Incidence Rate | 44.7 Number of patients/100 patient-years |
| Telmisartan 40mg and Amlodipine 10mg | Oedema Incidence Rate | 42.8 Number of patients/100 patient-years |
| Telmisartan 80mg and Amlodipine 10mg | Oedema Incidence Rate | 54.0 Number of patients/100 patient-years |
Secondary
Peripheral Oedema Incidence Rate
The number of cases of peripheral oedema (expressed as number of cases/100 patient-years)
Time frame: During randomised treatment period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amlodipine 10mg | Peripheral Oedema Incidence Rate | 48.8 Number of cases/100 patient-years |
| Telmisartan 40mg and Amlodipine 10mg | Peripheral Oedema Incidence Rate | 44.8 Number of cases/100 patient-years |
| Telmisartan 80mg and Amlodipine 10mg | Peripheral Oedema Incidence Rate | 54.0 Number of cases/100 patient-years |
Secondary
Trough Seated BP Normality Classes
The number of patients who reach predefined BP categories
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 10mg | Trough Seated BP Normality Classes | Stage 1 hypertension (SBP<160 and DBP<100 mmHg) | 157 Participants |
| Amlodipine 10mg | Trough Seated BP Normality Classes | High-normal (SBP<140 DBP<90 mmHg and not normal) | 77 Participants |
| Amlodipine 10mg | Trough Seated BP Normality Classes | Optimal (SBP<120 and DBP<80 mmHg) | 0 Participants |
| Amlodipine 10mg | Trough Seated BP Normality Classes | Normal (SBP<130 and DBP<85 mmHg and not optimal) | 36 Participants |
| Amlodipine 10mg | Trough Seated BP Normality Classes | Stage 2 hypertension (SBP>=160 and DBP>=100 mmHg) | 35 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated BP Normality Classes | High-normal (SBP<140 DBP<90 mmHg and not normal) | 91 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Optimal (SBP<120 and DBP<80 mmHg) | 12 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Normal (SBP<130 and DBP<85 mmHg and not optimal) | 43 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Stage 1 hypertension (SBP<160 and DBP<100 mmHg) | 139 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Stage 2 hypertension (SBP>=160 and DBP>=100 mmHg) | 21 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Stage 2 hypertension (SBP>=160 and DBP>=100 mmHg) | 15 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Stage 1 hypertension (SBP<160 and DBP<100 mmHg) | 133 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Optimal (SBP<120 and DBP<80 mmHg) | 6 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated BP Normality Classes | High-normal (SBP<140 DBP<90 mmHg and not normal) | 106 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated BP Normality Classes | Normal (SBP<130 and DBP<85 mmHg and not optimal) | 50 Participants |
p-value: 0.006Wilcoxon rank sum test
p-value: <0.001Wilcoxon rank sum test
Secondary
Trough Seated DBP Response
The number of patients who reach the target DBP of \<90mmHg or had a reduction in DBP \>= 10mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 10mg | Trough Seated DBP Response | Yes (Responder) | 163 Participants |
| Amlodipine 10mg | Trough Seated DBP Response | No (Non-responder) | 142 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated DBP Response | Yes (Responder) | 202 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated DBP Response | No (Non-responder) | 104 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated DBP Response | Yes (Responder) | 213 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated DBP Response | No (Non-responder) | 97 Participants |
p-value: 0.00295% CI: [1.21, 2.34]Mantel Haenszel
p-value: <0.00195% CI: [1.38, 2.68]Mantel Haenszel
Secondary
Trough Seated Diastolic Blood Pressure <80 mmHg
The number of patients who reach the target DBP of \<80mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 10mg | Trough Seated Diastolic Blood Pressure <80 mmHg | Yes (DBP<80 mmHg) | 18 Participants |
| Amlodipine 10mg | Trough Seated Diastolic Blood Pressure <80 mmHg | No (DBP>=80 mmHg) | 287 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure <80 mmHg | Yes (DBP<80 mmHg) | 39 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure <80 mmHg | No (DBP>=80 mmHg) | 267 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure <80 mmHg | Yes (DBP<80 mmHg) | 39 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure <80 mmHg | No (DBP>=80 mmHg) | 271 Participants |
p-value: 0.00495% CI: [1.3, 4.25]Mantel Haenszel
p-value: 0.00495% CI: [1.29, 4.22]Mantel Haenszel
Secondary
Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg)
The number of patients who reach the target DBP of \<90mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | Yes (DBP<90 mmHg) | 156 Participants |
| Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | No (DBP>=90 mmHg) | 149 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | Yes (DBP<90 mmHg) | 195 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | No (DBP>=90 mmHg) | 111 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | Yes (DBP<90 mmHg) | 206 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated Diastolic Blood Pressure Control (Defined as < 90mmHg) | No (DBP>=90 mmHg) | 104 Participants |
p-value: 0.00295% CI: [1.21, 2.32]Mantel Haenszel
p-value: <0.00195% CI: [1.37, 2.65]Mantel Haenszel
Secondary
Trough Seated SBP Control
The number of patients who reach the target SBP of \<140mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 10mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 153 Participants |
| Amlodipine 10mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 152 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 180 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 126 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated SBP Control | Yes (SBP<140 mmHg) | 187 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated SBP Control | No (SBP>=140 mmHg) | 123 Participants |
p-value: 0.02795% CI: [1.04, 2]Mantel Haenszel
p-value: 0.00895% CI: [1.12, 2.15]Mantel Haenszel
Secondary
Trough Seated SBP Response
The number of patients who reach the target SBP of \<140mmHg or had a reduction in SBP \>= 15 mmHg
Time frame: End of study (8 weeks or last value on treatment)
Population: Full analysis set of patients who had a baseline trough blood pressure measurement and at least one post baseline trough blood pressure measurement using last observation carried forward
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 10mg | Trough Seated SBP Response | Yes (Responder) | 165 Participants |
| Amlodipine 10mg | Trough Seated SBP Response | No (Non-responder) | 140 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated SBP Response | Yes (Responder) | 198 Participants |
| Telmisartan 40mg and Amlodipine 10mg | Trough Seated SBP Response | No (Non-responder) | 108 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated SBP Response | Yes (Responder) | 204 Participants |
| Telmisartan 80mg and Amlodipine 10mg | Trough Seated SBP Response | No (Non-responder) | 106 Participants |
p-value: 0.00695% CI: [1.14, 2.21]Mantel Haenszel
p-value: 0.00295% CI: [1.2, 2.32]Mantel Haenszel