An Active-controlled, Clinical Trial to Assess Central Hemodynamic Effects of Bisoprolol in Hypertensive Patients (Central Hemodynamic Assessment Measured in Patient With HypertensION [CHAMPION])
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Bisoprolol; Atenolol
Intervention type(s): Drug; Drug
Intervention description(s): Bisoprolol tablet will be administered orally at a dose of 5 milligram (mg) once daily in the morning for 12 weeks.; Atenolol tablet will be administered orally at a dose of 50 mg once daily in the morning for 12 weeks.
Other intervention name(s): CONCOR®; TENORMIN®
Intervention MeSH terms: Atenolol; Bisoprolol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bisoprolol; Atenolol; Hypertension; Blood pressure