HypertensionPhase 4NCT01101009
Comparison of Sevikar® and the Combination of Perindopril/Amlodipine on Central Blood Pressure
A Phase 4 study testing Perindopril + amlodipine + if necessary, hydrochlorothiazide and olmesartan/amlodipine + hydrochlorothiazide, if necessary. in people with Hypertension, run by Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company at 15 sites in Spain.
Trial summary
Comparison of the combination of amlodipine with an angiotensin receptor blocker or an angiotensin converting inhibitor, on central arterial blood pressure in patients with hypertension and additional risk factors. This is a randomised, double-blind, double-dummy, multicenter study. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Perindopril + amlodipine + if necessary, hydrochlorothiazide and olmesartan/amlodipine + hydrochlorothiazide, if necessary.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 486 participants
- Where
- 15 sitesSpain
- Study dates
- Apr 2010to Dec 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- moderate to severe hypertension
- 3 additional risk factors such as age > 55 (male), > 65 female, smoker, type 2 diabetes, obesity, cardiovascular disease, congestive heart failure, chronic kidney disease,
- ability to give informed consent
Who cannot join
- secondary or malignant hypertension
- contraindication to any of the study drugs
- Creatinine clearance level <40ml/min
- treatment with more than 3 antihypertensive drugs
- Myocardial infarction, percutaneous transluminal coronary angioplasty, cardiac bypass surgery < 6 month prior to start of the study,
- unstable angina pectoris,
Show all 11Show fewer
- stroke, transient ischemic attack < 3 months prior to start,
- Congestive heart failure NYHA II-IV,
- clinically relevant concomitant diseases,
- alcohol or drug abuse,
- pregnancy or women of childbearing potential without contraceptive precaution,
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Spain15 sites
Centro de Salud Casas Ibañez
Albacete, 02200
Hospital del Mar
Barcelona, 08003
Hospital General de Jerez de la Frontera
Cadiz, 11407
Hospital Universitario de Fuenlabrada
Fuenlabrada (Madrid)
Hospital Universitario La Princesa
Madrid, 28006
Hospital Universitario 12 Octubre
Madrid, 28041
Hospital General Universitario La Paz
Madrid
Hospital Universitario Clínico San Carlos
Madrid
Hospital Universitario de Móstoles
Madrid
Hospital Universitario Ramón y Cajal
Madrid
Hospital General Carlos Haya
Málaga
Centro de Salud Murcia San Andrés
Murcia
Hospital de Sagunto
Puerto de Sagunto (Valencia)
Centro de Salud La Alamedilla
Salamanca
Hospital Virgen de la Macarena
Seville, 41009
About this study
Official title: Efficacy of Sevikar® Compared to the Combination of Perindopril/ Amlodipine on Central Arterial Blood Pressure in Patients With Moderate to Severe Hypertension-
Comparison of the combination of amlodipine with an angiotensin receptor blocker or an angiotensin converting inhibitor, on central arterial blood pressure in patients with hypertension and additional risk factors. This is a randomised, double-blind, double-dummy, multicenter study. The duration of active treatment 24 weeks.
Read the detailed description
The study, multi-center balanced, parallel group (two treatment arms), randomized, double-blind (double-dummy), non-inferiority study is designed to show non-inferiority of Sevikar® (olmesartan(OM)/amlodipine (AM)) 40/10 mg compared to the combination of Perindopril (PER) 8 mg plus Amlodipine 10 mg with regard to central systolic blood pressure lowering effect, using the change from baseline (Week 0) to final examination (Week 24).
Male and female Caucasians aged ≥ 40 years and <80 years with moderate to severe hypertension, defined by a systolic blood pressure (SBP) ≥ 160 and ≤ 200 or diastolic blood pressure (DBP) ≥ 100 and ≤ 115 mmHg for untreated patients, SBP ≥ 140 or DBP ≥ 90 mmHg for insufficiently pre-treated patients and SBP ≥ 130 mmHg or DBP ≥ 80 mmHg for insufficiently pretreated diabetics chronic kidney disease will be eligible for participation. In addition,three additional risk factors should be present.
During the course of the study three central blood pressure measurements (at randomization, at week 12 and at termination) will be performed with SphygmoCor ultrasound method. The conventional measurements with calibrated tensiometers (Omron) will be performed at each visit. Ambulatory blood pressure monitoring will be performed at randomisation.
The study starts with a 2-4 week run in phase. AM will be given as open-labelled 5 mg or 10 mg tablets, administered once daily. After randomization during the double-blind phase, study medication will comprise either OM/AM 40/10 mg or PER 8 mg (2x4 mg) plus AM 10 mg and will be administered once daily. Furthermore, open-label HCTZ 12.5 mg and 25.0 mg will be provided in tablets and administered once daily according to the treatment schedule.
The primary endpoint is the change in central SBP from baseline (Week 0, Visit 0) to final examination (Week 24, Visit 5) using Last Observation Carried Forward (LOCF) approach.
The study is conducted in approximately 15 centres in Spain. Depending on the previously administered drugs the run in phase is up to four weeks (Visits -2 and -1). Individual duration of active treatment (after randomization) will last 24 weeks (Visits 0-5). The total individual duration is 28 weeks.
A total of 518 patients (259 patients/arm) will be needed in the Per Protocol Set (PPS) for the confirmatory primary analysis using mean change from baseline (Week 0) to Final Examination assuming a drop out rate of 20% during Run-in Phase a total of 720 patients have to be screened in order to achieve 576 (288 patients/arm) randomised patients.
Assuming approximately 10% major protocol deviations, a total of 518 patients will remain in the PPS.
- Conditions
- Hypertension
- Being tested
- Perindopril + amlodipine + if necessary, hydrochlorothiazide, olmesartan/amlodipine + hydrochlorothiazide, if necessary.
- Keywords
- Sevikar®, Central Arterial Blood Pressure
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Perindopril + amlodipine + if necessary, hydrochlorothiazideDrug
Two perindopril 4 mg tablets + 1 amlodipine 10 mg tablet + placebo tablet matching the olmesartan/amlodipine tablet. All tablets are taken once daily. The duration of administration of perindopril tablets and placebo is 24 weeks. The duration of administration of amlodipine tablets is 24-26 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary
olmesartan/amlodipine + hydrochlorothiazide, if necessary.Drug
olmesartan/amlodipine tablets 40 mg/10 mg, + placebo tablets matching the perindopril tablet and amlodipine tablet. All tablets are taken once daily for 24 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary
| Study group | Role | What they receive |
|---|---|---|
| Perindopril+amlodipine | Active comparator | Not described Receives: Drug: Perindopril + amlodipine + if necessary, hydrochlorothiazide |
| Olmesartan/amlodipine | Active comparator | Not described Receives: Drug: olmesartan/amlodipine + hydrochlorothiazide, if necessary. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in central systolic blood pressure from baseline (Week 0, Visit 0) to Final Examination (Week 24, Visit 5) using last observation carried forward approach.
Measured: Baseline to week 24
Secondary outcomes (7)
Changes in systolic and diastolic ambulatory blood pressure (mean of 24h, daytime and night-time)
Measured: Baseline to week 24
Changes in conventional mean sitting systolic and diastolic blood pressure measurement
Measured: Baseline to 24 weeks
Incidence and profile of AEs separately by Run-in Phase and by double-blind Treatment Phase
Measured: Run in phase (2 weeks) to end of study (24 weeks)
Number of responders at Final Examination defined as normalized or a decrease of systolic blood pressure by at least 20 mmHg or diastolic blood pressure by at least 10 mmHg in conventional BP measurements.
Measured: Baseline to 24 weeks
Number of normalized at Final Examination (defined as blood pressure <140/90 mmHg or <130/80 mmHg in diabetics/chronic kidney disease, in conventional BP measurements.
Measured: Baseline to 24 weeks
Changes in mean sitting systolic and diastolic blood pressure (BP) measurements from week 12 to Final Exam in patients with stabilized BP (BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) from Week 12 and Week 18.
Measured: Week 12 to Week 18 or week 24
Changes in Central Systolic Blood Pressure from week 12 to Final Examination in patients with stabilised BP (i.e. patients whose BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) between Week 12 and Week 18.
Measured: Week 12 to week 18 or week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionNov 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 486 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01101009
- Sponsor's protocol ID
- DSE- SEV-02-09
- Other IDs
- 2009-012966-30, 2009
- Status last verified
- Jan 2013
- First submitted
- 7 Apr 2010
- Last updated
- 24 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Publications
Ruilope L, Schaefer A. The fixed-dose combination of olmesartan/amlodipine was superior in central aortic blood pressure reduction compared with perindopril/amlodipine: a randomized, double-blind trial in patients with hypertension. Adv Ther. 2013 Dec;30(12):1086-99. doi: 10.1007/s12325-013-0076-6. Epub 2013 Nov 30.
PubMed 24293132Ruilope LM, Schaefer A. Efficacy of Sevikar(R) compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study. Contemp Clin Trials. 2011 Sep;32(5):710-6. doi: 10.1016/j.cct.2011.04.011. Epub 2011 May 14.
PubMed 21586342
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Sevikar® Compared to the Combination of Perindopril/ Amlodipine on Central Arterial Blood Pressure in Patients With Moderate to Severe Hypertension-
- ClinicalTrials.gov ID
- NCT01101009
- Acronym / sponsor ID
- DSE- SEV-02-09
- Conditions
- Hypertension
- Keywords
- Sevikar®, Central Arterial Blood Pressure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 486 participants (actual)
- Lead sponsor
- Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo CompanyIndustry (pharma, biotech, devices)
- Study start
- Apr 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 9 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Comparison of the combination of amlodipine with an angiotensin receptor blocker or an angiotensin converting inhibitor, on central arterial blood pressure in patients with hypertension and additional risk factors. This is a randomised, double-blind, double-dummy, multicenter study. The duration of active treatment 24 weeks.
Detailed description
The study, multi-center balanced, parallel group (two treatment arms), randomized, double-blind (double-dummy), non-inferiority study is designed to show non-inferiority of Sevikar® (olmesartan(OM)/amlodipine (AM)) 40/10 mg compared to the combination of Perindopril (PER) 8 mg plus Amlodipine 10 mg with regard to central systolic blood pressure lowering effect, using the change from baseline (Week 0) to final examination (Week 24).
Male and female Caucasians aged ≥ 40 years and <80 years with moderate to severe hypertension, defined by a systolic blood pressure (SBP) ≥ 160 and ≤ 200 or diastolic blood pressure (DBP) ≥ 100 and ≤ 115 mmHg for untreated patients, SBP ≥ 140 or DBP ≥ 90 mmHg for insufficiently pre-treated patients and SBP ≥ 130 mmHg or DBP ≥ 80 mmHg for insufficiently pretreated diabetics chronic kidney disease will be eligible for participation. In addition,three additional risk factors should be present.
During the course of the study three central blood pressure measurements (at randomization, at week 12 and at termination) will be performed with SphygmoCor ultrasound method. The conventional measurements with calibrated tensiometers (Omron) will be performed at each visit. Ambulatory blood pressure monitoring will be performed at randomisation.
The study starts with a 2-4 week run in phase. AM will be given as open-labelled 5 mg or 10 mg tablets, administered once daily. After randomization during the double-blind phase, study medication will comprise either OM/AM 40/10 mg or PER 8 mg (2x4 mg) plus AM 10 mg and will be administered once daily. Furthermore, open-label HCTZ 12.5 mg and 25.0 mg will be provided in tablets and administered once daily according to the treatment schedule.
The primary endpoint is the change in central SBP from baseline (Week 0, Visit 0) to final examination (Week 24, Visit 5) using Last Observation Carried Forward (LOCF) approach.
The study is conducted in approximately 15 centres in Spain. Depending on the previously administered drugs the run in phase is up to four weeks (Visits -2 and -1). Individual duration of active treatment (after randomization) will last 24 weeks (Visits 0-5). The total individual duration is 28 weeks.
A total of 518 patients (259 patients/arm) will be needed in the Per Protocol Set (PPS) for the confirmatory primary analysis using mean change from baseline (Week 0) to Final Examination assuming a drop out rate of 20% during Run-in Phase a total of 720 patients have to be screened in order to achieve 576 (288 patients/arm) randomised patients.
Assuming approximately 10% major protocol deviations, a total of 518 patients will remain in the PPS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perindopril+amlodipine | Active comparator | Drug: Perindopril + amlodipine + if necessary, hydrochlorothiazide |
| Olmesartan/amlodipine | Active comparator | Drug: olmesartan/amlodipine + hydrochlorothiazide, if necessary. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- moderate to severe hypertension
- 3 additional risk factors such as age > 55 (male), > 65 female, smoker, type 2 diabetes, obesity, cardiovascular disease, congestive heart failure, chronic kidney disease,
- ability to give informed consent
Key exclusion criteria (11 listed)
- secondary or malignant hypertension
- contraindication to any of the study drugs
- Creatinine clearance level <40ml/min
- treatment with more than 3 antihypertensive drugs
- Myocardial infarction, percutaneous transluminal coronary angioplasty, cardiac bypass surgery < 6 month prior to start of the study,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Perindopril + amlodipine + if necessary, hydrochlorothiazideTwo perindopril 4 mg tablets + 1 amlodipine 10 mg tablet + placebo tablet matching the olmesartan/amlodipine tablet. All tablets are taken once daily. The duration of administration of perindopril tablets and placebo is 24 weeks. The duration of administration of amlodipine tablets is 24-26 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary | Drug | Perindopril+amlodipine |
| olmesartan/amlodipine + hydrochlorothiazide, if necessary.olmesartan/amlodipine tablets 40 mg/10 mg, + placebo tablets matching the perindopril tablet and amlodipine tablet. All tablets are taken once daily for 24 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary | Drug | Olmesartan/amlodipine |
Primary outcome
Change in central systolic blood pressure from baseline (Week 0, Visit 0) to Final Examination (Week 24, Visit 5) using last observation carried forward approach.
Time frame: Baseline to week 24
7 secondary outcomes
Changes in systolic and diastolic ambulatory blood pressure (mean of 24h, daytime and night-time)
Time frame: Baseline to week 24
Changes in conventional mean sitting systolic and diastolic blood pressure measurement
Time frame: Baseline to 24 weeks
Incidence and profile of AEs separately by Run-in Phase and by double-blind Treatment Phase
Time frame: Run in phase (2 weeks) to end of study (24 weeks)
Number of responders at Final Examination defined as normalized or a decrease of systolic blood pressure by at least 20 mmHg or diastolic blood pressure by at least 10 mmHg in conventional BP measurements.
Time frame: Baseline to 24 weeks
Number of normalized at Final Examination (defined as blood pressure <140/90 mmHg or <130/80 mmHg in diabetics/chronic kidney disease, in conventional BP measurements.
Time frame: Baseline to 24 weeks
Changes in mean sitting systolic and diastolic blood pressure (BP) measurements from week 12 to Final Exam in patients with stabilized BP (BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) from Week 12 and Week 18.
Time frame: Week 12 to Week 18 or week 24
Changes in Central Systolic Blood Pressure from week 12 to Final Examination in patients with stabilised BP (i.e. patients whose BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) between Week 12 and Week 18.
Time frame: Week 12 to week 18 or week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2018.
- Derived from this study: PubMed 24293132Ruilope L, Schaefer A. The fixed-dose combination of olmesartan/amlodipine was superior in central aortic blood pressure reduction compared with perindopril/amlodipine: a randomized, double-blind trial in patients with hypertension. Adv Ther. 2013 Dec;30(12):1086-99. doi: 10.1007/s12325-013-0076-6. Epub 2013 Nov 30.
- Derived from this study: PubMed 21586342Ruilope LM, Schaefer A. Efficacy of Sevikar(R) compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study. Contemp Clin Trials. 2011 Sep;32(5):710-6. doi: 10.1016/j.cct.2011.04.011. Epub 2011 May 14.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Perindopril + amlodipine + if necessary, hydrochlorothiazide and olmesartan/amlodipine + hydrochlorothiazide, if necessary. in people with Hypertension, run by Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company at 15 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in central systolic blood pressure from baseline (Week 0, Visit 0) to Final Examination (Week 24, Visit 5) using last observation carried forward approach. (time frame: Baseline to week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01101009, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2018.