HypertensionPhase 4NCT01079962
An Active-controlled, Clinical Trial to Assess Central Hemodynamic Effects of Bisoprolol in Hypertensive Patients (Central Hemodynamic Assessment Measured in Patient With HypertensION [CHAMPION])
A Phase 4 study testing Bisoprolol and Atenolol in people with Hypertension, run by Merck KGaA, Darmstadt, Germany at 1 site in South Korea.
Trial summary
Antihypertensive drugs aim to reduce blood pressure (BP) either through decrease of the total peripheral resistance through vasodilatation at the level of arterioles (microcirculation) or by decreasing the cardiac output through reduction of the stroke volume or heart rate or both. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Bisoprolol and Atenolol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 209 participants
- Where
- 1 siteSouth Korea
- Study dates
- Dec 2009to Oct 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- An antihypertensive-naive subject or a subject who has not been taking the previously administered antihypertensive agent for at least 4 weeks prior to screening
- Subjects aged between 20 and 75 years, inclusive
- Subjects with systolic blood pressure (SBP) greater than or equal to 140 millimeter of mercury (mmHg) and less than 180 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg and less than 110 mmHg
Who cannot join
- Subjects with secondary hypertension
- Subjects with renal impairment (Creatinine greater than 150 micromoles/liter [mcmol/L] or Creatinine greater than 1.7 mg/deciliter [dL])
- Subjects with severe hypertension (Stage III) SBP greater than or equal to 180 mmHg or DBP greater than or equal to 110 mmHg
- Subjects with congestive heart failure, acute myocardial infarction, unstable angina
- Subjects with moderate bronchial asthma, chronic obstructive pulmonary disease
- Subjects with symptomatic bradycardia, radial artery injury, second degree or third degree atrioventricular (AV) block, atrial fibrillation, atrial flutter, left bundle branch block (LBBB)
- Subjects with a history of hypersensitivity to bisoprolol and atenolol products
- Pregnancy or breastfeeding women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Multi-center, Randomized, Open-label, Clinical Trial to Compare the Aortic Pulse Pressure Effects of Bisoprolol and Atenolol in 12 Weeks Treatment of Hypertension
Antihypertensive drugs aim to reduce blood pressure (BP) either through decrease of the total peripheral resistance through vasodilatation at the level of arterioles (microcirculation) or by decreasing the cardiac output through reduction of the stroke volume or heart rate or both. On the other hand, all antihypertensive drugs might potentially decrease arterial stiffness passively with the reduction of the distending pressure or with the resynchronization of the reflected pressure wave. With theses potential mechanisms, it is also expected that these drugs might exert a favorable effect on pulse pressure amplification between central and peripheral arteries.
However, there is solid evidence that the widely applied antihypertensive drugs have differential effect on brachial and central BP. Several reports in the past have confirmed the potential hypothesis that beta blockers decrease central BP less than the observed reduction at the level of the brachial artery. It has been hypothesized that deceleration of heart rate and the re synchronizing the reflected pressure wave earlier in the systolic phase seems to be the leading cause of non-favorable effect of beta blockers on central BP, these effects might be partially counterbalanced in beta blockers with high beta-1 selectivity resulting in less peripheral vasoconstriction properties.
Read the detailed description
Central pulse pressure is a better predictor of left ventricular mass and carotid intima thickness, and the conventional peripheral BP does not seem to be an accurate reflection of central arterial BP. The pulse pressure amplification between peripheral and central arteries reflects the left ventricular afterload, subendothelial viability, and the intensity of cyclic stress imposed to the renal and cerebral micro- and macro vessels. As central hemodynamic parameters are independently associated with organ damage and are closely related to important cardiovascular outcome, it is suggested that the new clinical trials on antihypertensive drug treatment should compare simultaneously the chronic effect of drugs on both peripheral and central BP.
OBJECTIVES
Primary objective:
- To assess the effect of bisoprolol versus atenolol on the aortic pulse pressure as a central hemodynamic index in subjects with hypertension
Secondary objectives:
- To assess the effect of bisoprolol versus atenolol on the aortic BP as a central hemodynamic index in subjects with hypertension
- To assess the effect of bisoprolol versus atenolol on the AIx and cfPWV as arterial stiffness indexes in subjects with hypertension
- To assess the effect of bisoprolol versus atenolol on the aortic pulse pressure as a central hemodynamic index at interim visit (Visit 4)
- To assess the effect of bisoprolol versus atenolol on the lipid profile and serum glucose as metabolism indexes
- To assess the effect of bisoprolol versus atenolol on the brachial BP as a peripheral BP index in subjects with hypertension
- To assess the safety and tolerability of bisoprolol versus atenolol in subjects with hypertension
The present study will be approximately of 14 weeks duration comprising of 1 week screening, followed by a 12 weeks treatment period and a 2 weeks post study follow up contact conducted via telephone to monitor additional serious adverse experiences.
There will be 4 scheduled visits (at Day -7, Day 0, Week 4 and Week 12). After screening period in which eligibility criteria were confirmed, subjects with hypertension will be randomized in a 1:1 ratio to receive treatment with either bisoprolol or atenolol. Hemodynamic measurements will be made at baseline, Week 4, Week 12 and biochemical measurements will be made at baseline (Day 0) and at Week 12.
- Conditions
- Hypertension
- Being tested
- Bisoprolol, Atenolol
- Keywords
- Bisoprolol, Atenolol, Hypertension, 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.
BisoprololDrug
Also called CONCOR®
Bisoprolol tablet will be administered orally at a dose of 5 milligram (mg) once daily in the morning for 12 weeks.
AtenololDrug
Also called TENORMIN®
Atenolol tablet will be administered orally at a dose of 50 mg once daily in the morning for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Bisoprolol | Experimental | Not described Receives: Drug: Bisoprolol |
| Atenolol | Active comparator | Not described Receives: Drug: Atenolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline.
Measured: Baseline and Week 12
Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline.
Measured: Baseline and Week 12
Secondary outcomes (9)
Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12
The change in aortic BP (aortic systolic blood pressure [SBP], aortic diastolic blood pressure [DBP] and aortic mean blood pressure [BP]) at Week 4 and Week 12 was calculated as aortic BP (aortic SBP, aortic DBP and aortic mean BP) at Week 4 and Week 12 minus aortic BP (aortic SBP, aortic DBP and aortic mean BP) at baseline.
Measured: Baseline, Week 4 and Week 12
Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12
Augmentation index is a composite measure of wave reflection and systemic arterial stiffness which was calculated as the difference between the second and first systolic peaks. The change in AIx at Week 4 and Week 12 was calculated as AIx at Week 4 and Week 12 minus AIx at baseline.
Measured: Baseline, Week 4 and Week 12
Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12
Pulse wave velocity (PWV) is used as a measure of arterial stiffness, which is a measure of the cushioning functioning of major vessels like the aorta. The velocity of the Pulse wave (PW) along an artery is dependent on the stiffness of that artery. The change in cfPWV at Week 4 and Week 12 was calculated as cfPWV at Week 4 and Week 12 minus cfPWV at baseline.
Measured: Baseline, Week 4 and Week 12
Change From Baseline in Heart Rate at Week 4 and Week 12
The change in heart rate at Week 4 and Week 12 was calculated as heart rate at Week 4 and Week 12 minus heart rate at baseline.
Measured: Baseline, Week 4 and Week 12
Change From Baseline in Aortic Pulse Pressure (APP) at Week 4
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 4 was calculated as APP at Week 4 minus APP at baseline.
Measured: Baseline and Week 4
Change From Baseline in Lipid Levels at Week 12
The lipid levels evaluated were total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol blood concentrations. The change in lipid levels at Week 12 was calculated as lipid levels at Week 12 minus lipid levels at baseline.
Measured: Baseline and Week 12
Change From Baseline in Blood Glucose Levels at Week 12
The change in blood glucose level at Week 12 was calculated as blood glucose level at Week 12 minus blood glucose level at baseline.
Measured: Baseline and Week 12
Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12
The change in brachial BP (brachial SBP, brachial DBP and brachial mean BP) at Week 4 and Week 12 was calculated as brachial BP (brachial SBP, brachial DBP and brachial mean BP) at Week 4 and Week 12 minus brachial BP (brachial SBP, brachial DBP and brachial mean BP) at baseline.
Measured: Baseline, Week 4 and Week 12
Number of Participants With Adverse Events (AEs)
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Measured: Baseline up to Week 14 (follow-up visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2010 (estimated)
- Study startDec 2009
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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
- None (open label)
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Ltd.
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck Ltd., Korea, an affiliate of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01079962
- Sponsor's protocol ID
- EMD 084000-505
- Status last verified
- Jan 2014
- First submitted
- 2 Mar 2010
- Last updated
- 13 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Park S, Rhee MY, Lee SY, Park SW, Jeon D, Kim BW, Kwan J, Choi D. A prospective, randomized, open-label, active-controlled, clinical trial to assess central haemodynamic effects of bisoprolol and atenolol in hypertensive patients. J Hypertens. 2013 Apr;31(4):813-9. doi: 10.1097/HJH.0b013e32835e8f5b.
PubMed 23385648
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-center, Randomized, Open-label, Clinical Trial to Compare the Aortic Pulse Pressure Effects of Bisoprolol and Atenolol in 12 Weeks Treatment of Hypertension
- ClinicalTrials.gov ID
- NCT01079962
- Acronym / sponsor ID
- EMD 084000-505
- Conditions
- Hypertension
- Keywords
- Bisoprolol, Atenolol, Hypertension, Blood pressure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Ltd.
- Study start
- Dec 2009
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 3 Mar 2010 (estimated)
- Results
- Posted 2 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antihypertensive drugs aim to reduce blood pressure (BP) either through decrease of the total peripheral resistance through vasodilatation at the level of arterioles (microcirculation) or by decreasing the cardiac output through reduction of the stroke volume or heart rate or both. On the other hand, all antihypertensive drugs might potentially decrease arterial stiffness passively with the reduction of the distending pressure or with the resynchronization of the reflected pressure wave. With theses potential mechanisms, it is also expected that these drugs might exert a favorable effect on pulse pressure amplification between central and peripheral arteries.
However, there is solid evidence that the widely applied antihypertensive drugs have differential effect on brachial and central BP. Several reports in the past have confirmed the potential hypothesis that beta blockers decrease central BP less than the observed reduction at the level of the brachial artery. It has been hypothesized that deceleration of heart rate and the re synchronizing the reflected pressure wave earlier in the systolic phase seems to be the leading cause of non-favorable effect of beta blockers on central BP, these effects might be partially counterbalanced in beta blockers with high beta-1 selectivity resulting in less peripheral vasoconstriction properties.
Detailed description
Central pulse pressure is a better predictor of left ventricular mass and carotid intima thickness, and the conventional peripheral BP does not seem to be an accurate reflection of central arterial BP. The pulse pressure amplification between peripheral and central arteries reflects the left ventricular afterload, subendothelial viability, and the intensity of cyclic stress imposed to the renal and cerebral micro- and macro vessels. As central hemodynamic parameters are independently associated with organ damage and are closely related to important cardiovascular outcome, it is suggested that the new clinical trials on antihypertensive drug treatment should compare simultaneously the chronic effect of drugs on both peripheral and central BP.
OBJECTIVES
Primary objective:
- To assess the effect of bisoprolol versus atenolol on the aortic pulse pressure as a central hemodynamic index in subjects with hypertension
Secondary objectives:
- To assess the effect of bisoprolol versus atenolol on the aortic BP as a central hemodynamic index in subjects with hypertension
- To assess the effect of bisoprolol versus atenolol on the AIx and cfPWV as arterial stiffness indexes in subjects with hypertension
- To assess the effect of bisoprolol versus atenolol on the aortic pulse pressure as a central hemodynamic index at interim visit (Visit 4)
- To assess the effect of bisoprolol versus atenolol on the lipid profile and serum glucose as metabolism indexes
- To assess the effect of bisoprolol versus atenolol on the brachial BP as a peripheral BP index in subjects with hypertension
- To assess the safety and tolerability of bisoprolol versus atenolol in subjects with hypertension
The present study will be approximately of 14 weeks duration comprising of 1 week screening, followed by a 12 weeks treatment period and a 2 weeks post study follow up contact conducted via telephone to monitor additional serious adverse experiences.
There will be 4 scheduled visits (at Day -7, Day 0, Week 4 and Week 12). After screening period in which eligibility criteria were confirmed, subjects with hypertension will be randomized in a 1:1 ratio to receive treatment with either bisoprolol or atenolol. Hemodynamic measurements will be made at baseline, Week 4, Week 12 and biochemical measurements will be made at baseline (Day 0) and at Week 12.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bisoprolol | Experimental | Drug: Bisoprolol |
| Atenolol | Active comparator | Drug: Atenolol |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- An antihypertensive-naive subject or a subject who has not been taking the previously administered antihypertensive agent for at least 4 weeks prior to screening
- Subjects aged between 20 and 75 years, inclusive
- Subjects with systolic blood pressure (SBP) greater than or equal to 140 millimeter of mercury (mmHg) and less than 180 mmHg or diastolic blood pressure (DBP) greater than or equal to 90 mmHg and less than 110 mmHg
Key exclusion criteria (8 listed)
- Subjects with secondary hypertension
- Subjects with renal impairment (Creatinine greater than 150 micromoles/liter [mcmol/L] or Creatinine greater than 1.7 mg/deciliter [dL])
- Subjects with severe hypertension (Stage III) SBP greater than or equal to 180 mmHg or DBP greater than or equal to 110 mmHg
- Subjects with congestive heart failure, acute myocardial infarction, unstable angina
- Subjects with moderate bronchial asthma, chronic obstructive pulmonary disease
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 |
|---|---|---|
| BisoprololAlso: CONCOR®Bisoprolol tablet will be administered orally at a dose of 5 milligram (mg) once daily in the morning for 12 weeks. | Drug | Bisoprolol |
| AtenololAlso: TENORMIN®Atenolol tablet will be administered orally at a dose of 50 mg once daily in the morning for 12 weeks. | Drug | Atenolol |
Primary outcome
Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12
Time frame: Baseline and Week 12
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline.
Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12
Time frame: Baseline and Week 12
The APP was calculated as aortic systolic pressure minus aortic diastolic pressure. The change in APP at Week 12 was calculated as APP at Week 12 minus APP at baseline.
9 secondary outcomes
Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12
Time frame: Baseline, Week 4 and Week 12
Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12
Time frame: Baseline, Week 4 and Week 12
Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12
Time frame: Baseline, Week 4 and Week 12
Change From Baseline in Heart Rate at Week 4 and Week 12
Time frame: Baseline, Week 4 and Week 12
Change From Baseline in Aortic Pulse Pressure (APP) at Week 4
Time frame: Baseline and Week 4
Change From Baseline in Lipid Levels at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Blood Glucose Levels at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12
Time frame: Baseline, Week 4 and Week 12
Number of Participants With Adverse Events (AEs)
Time frame: Baseline up to Week 14 (follow-up visit)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23385648Park S, Rhee MY, Lee SY, Park SW, Jeon D, Kim BW, Kwan J, Choi D. A prospective, randomized, open-label, active-controlled, clinical trial to assess central haemodynamic effects of bisoprolol and atenolol in hypertensive patients. J Hypertens. 2013 Apr;31(4):813-9. doi: 10.1097/HJH.0b013e32835e8f5b.
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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.
Medical Responsible study director
Merck Ltd., Korea, an affiliate of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bisoprolol and Atenolol in people with Hypertension, run by Merck KGaA, Darmstadt, Germany at 1 site in South Korea.
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 8 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 13 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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?
Yes. Results are posted in the registry (first posted 2 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12 (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. 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 NCT01079962, which also lists 1 linked publication.
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 13 Feb 2014; AzTrials last refreshed its copy on 3 Nov 2026.