Comparison of Effect of cARvedilol Compared To bISoprolol on cenTral Pulse Pressure in Hypertension (ARTIST) Study

The purpose of this study is to compare of carvedilol, a vasodilating beta-blocker and bisoprolol, a beta1- selective beta-blocker for reducing the central pulse pressure and thereby left ventricular (LV) mass in never-treated hypertensive patients.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Drug: carvedilol; Drug: bisoprolol

Detailed Description

Carvedilol and bisoprolol are established beta-blockers for treating hypertension or chronic heart failure because these beta-blockers have cardio-protective effects. Recent studies have shown that the change in central pulse pressure is more closely associated with the change in cardiac load than the change in brachial pressure during hypertension treatment. Vasodilating beta-blockers may decrease central pulse pressure more than beta1- selective beta-blockers, because vasodilators reduced the magnitude of reflection wave by dilating peripheral muscular arteries. The investigators hypothesized that carvedilol, a vasodilating beta-blocker, would be more effective than bisoprolol, a beta1- selective beta-blocker in reducing central pulse pressure and thereby LV mass, through the reduction in the magnitude of reflection wave. The aim of the present study was to test this hypothesis in an active controlled, 2-arm parallel group comparison, prospective randomized open blinded end-point (PROBE) design study. At least 100 patients will be enrolled in each group and the follow up duration will be 48 weeks. The primary endpoint is to compare the change in central pulse pressure between the two groups.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yoshio Matsui; Phone Number: +81-285-58-7538; Email: yoshio@jichi.ac.jp

Study Locations

• Japan
  • Yamaguchi, Japan
    • Recruiting
    • Iwakuni City Medical Center
    • Contact: Yoshio Matsui; Phone Number: +81-827-21-3211; Email: yoshio@jichi.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Never-treated hypertensive subjects, aged 20-80 years (at the time of informed consent), regardless of sex
• Clinic systolic BP/diastolic BP > 140/90 mmHg in a sitting position.

Exclusion Criteria:

• Beta-blocker contraindications(asthma, COPD…)
• Heart rate less than 55 bpm
• Subjects treated with nitrates
• Grade 3 hypertension (≥180 and/or ≥110 mmHg)
• Secondary hypertension or malignant hypertension
• History of heart failure, coronary artery disease, and stroke
• Arrhythmia
• Renal dysfunction (serum creatinine ≥2.0 mg/dl)
• Hepatic dysfunction (AST and/or ALT ≥100 IU/l)
• A history of or a suspected malignant tumor within 5 years of enrollment
• Chronic inflammatory disease
• Pregnancy, childbearing potential with inadequate contraception, breast feeding
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: carvedilol; carvedilol is administered after randomization at a dose of 10 mg once daily, and if needed, titrated to 15 mg and to a maximum of 20 mg to achieve a clinic BP <140/90 mmHg.	Drug: carvedilol; carvedilol is administered after randomization at a dose of 10 mg once daily, and if needed, titrated to 15 mg and to a maximum of 20 mg to achieve a clinic BP <140/90 mmHg.
Experimental: bisoprolol; bisoprolol is administered after randomization at a dose of 2.5 mg once daily, and if needed, titrated to 3.75 mg and to a maximum of 5.0 mg to achieve a clinic BP <140/90 mmHg.	Drug: bisoprolol; bisoprolol is administered after randomization at a dose of 2.5 mg once daily, and if needed, titrated to 3.75 mg and to a maximum of 5.0 mg to achieve a clinic BP <140/90 mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in central pulse pressure (pulse pressure amplification)	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in LV mass index Changes in LV diastolic functions (E/Em, left atrium volume) Changes in urinary albumin excretion, B-type natriuretic peptide (BNP), HOMA-IR, and oxidative stress (urinary 8-isoprostane). Change in ambulatory BP	12 months

Collaborators and Investigators

• Sponsor: Yoshio Matsui
• Investigators: Principal Investigator: Kazuomi Kario, Jichi Medical University

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): April 1, 2013

Study Registration Dates

• First Submitted: November 18, 2010
• First Submitted That Met QC Criteria: November 18, 2010
• First Posted (Estimate): November 19, 2010

Study Record Updates

• Last Update Posted (Estimate): July 19, 2012
• Last Update Submitted That Met QC Criteria: July 18, 2012
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Hypertension, carvedilol, bisoprolol, central pulse pressure, pulse pressure amplification, reflection magnitude, LV mass index, LV diastolic function
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Bisoprolol; Carvedilol
• Other Study ID Numbers: ARTIST