Clinical trial NCT01079962: An Active-controlled, Clinical Trial to Assess Central Hemodynamic Effects of Bisoprolol in Hypertensive Patients (Central Hemodynamic Assessment Measured in Patient With HypertensION [CHAMPION])
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Bisoprolol
Atenolol
Hypertension
Blood pressure
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Ltd.
First posted: 2010-03-03
Enrollment: 209
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Aortic Pulse Pressure (APP) in Intention to Treat (ITT) Population at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Aortic Pulse Pressure (APP) in Per Protocol (PP) Population at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in Aortic Blood Pressure (BP) at Week 4 and Week 12
timeFrame: Baseline, Week 4 and Week 12
measure: Change From Baseline in Aortic Augmentation Index (AIx) at Week 4 and Week 12
timeFrame: Baseline, Week 4 and Week 12
measure: Change From Baseline in Carotid-femoral Pulse Wave Velocity (cfPWV) at Week 4 and Week 12
timeFrame: Baseline, Week 4 and Week 12
measure: Change From Baseline in Heart Rate at Week 4 and Week 12
timeFrame: Baseline, Week 4 and Week 12
measure: Change From Baseline in Aortic Pulse Pressure (APP) at Week 4
timeFrame: Baseline and Week 4
measure: Change From Baseline in Lipid Levels at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Blood Glucose Levels at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Brachial Blood Pressure (BP) at Week 4 and Week 12
timeFrame: Baseline, Week 4 and Week 12
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to Week 14 (follow-up visit)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hosptial, 250, Seongsanno, Seodaemungu
Study officials:
affiliation: Merck Ltd., Korea, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: 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.