An Active-controlled, Clinical Trial to Assess Central Hemodynamic Effects of Bisoprolol in Hypertensive Patients (Central Hemodynamic Assessment Measured in Patient With HypertensION [CHAMPION])

NCT ID: NCT01079962

Last Updated: 2014-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 209 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2011-10-31

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bisoprolol

Group Type: EXPERIMENTAL

Bisoprolol

Intervention Type: DRUG

Bisoprolol tablet will be administered orally at a dose of 5 milligram (mg) once daily in the morning for 12 weeks.

Atenolol

Group Type: ACTIVE_COMPARATOR

Atenolol

Intervention Type: DRUG

Atenolol tablet will be administered orally at a dose of 50 mg once daily in the morning for 12 weeks.

Interventions

Bisoprolol

Bisoprolol tablet will be administered orally at a dose of 5 milligram (mg) once daily in the morning for 12 weeks.

Intervention Type: DRUG

Atenolol

Atenolol tablet will be administered orally at a dose of 50 mg once daily in the morning for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

CONCOR®; TENORMIN®

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Ltd.

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Ltd., Korea, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

Severance Hosptial, 250, Seongsanno, Seodaemungu

Seoul, , South Korea

Countries

South Korea

References

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.

Reference Type: DERIVED

PMID: 23385648 (View on PubMed)

Other Identifiers

EMD 084000-505

Identifier Type: -

Identifier Source: org_study_id