Irbesartan and Atenolol in Hypertensive Heart Disease (SILVHIA)

May 3, 2015 updated by: Thomas Kahan, Karolinska Institutet

Randomized, Double-blind Evaluation of the Effects of Irbesartan and Atenolol on Cardiovascular Structure and Function in Subjects With Hypertension and Left Ventricular Hypertrophy

The renin-angiotensin-aldosterone system has been implicated in the control of structural changes of the heart and the vasculature, beyond the effects on blood pressure.

This projects examines the importance of the renin-angiotensin-aldosterone system and the sympathetic nervous system in the control of cardiac and vascular structure and function in subjects with hypertension.Patients with hypertension and left ventricular hypertrophy were randomized to an angiotensin receptor blocker or a beta adrenergic receptor blocker for 48 weeks. Repeat investigations of blood pressure, structure and function of the heart and the vascular tree, and neurohormones were performed. Two control groups, consisting of normotensive subjects and of hypertensive subjects with no cardiac hypertrophy were also examined for comparison.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

We included 115 patients with hypertension and cardiac hypertrophy, established by echocardiography. Extensive echocardiographic examinations, ultrasonography of the carotid arteries, 24h Holter registrations, 24h ambulatory blood pressure monitoring monitoring, neurohormones and blood samples for inflammation and hemostasis markers and endothelial function were done at weeks 0, 12, 24, and 48. Matched control groups (1:3, i.e. 38 normotensive subjects and 38 hypertensive subjects with no signs of hypertensive heart disease were examined at one occasion. All patients obtained irbesartan or atenolol for 12 weeks; a diuretic and a calcium antagonist was added when needed thereafter in order to obtained a blood pressure below 140/90 mm Hg. All analyses were performed central in a core laboratory.

Study Type

Interventional

Enrollment (Actual)

115

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, SE-182 88
        • Karolinska Institutet, Daprtment of Clinical Sciences, Danderyd Hospital, Cardiovascular Research Laboratory

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • At least 18 ys old
  • Male or female with no child bearing potential
  • Seated blood pressure diastolic 90-115 mm Hg
  • Left ventricular mass above 131 g/m2 for men, above 100 g/m2 for women
  • Informed consent

Exclusion Criteria:

  • Coronary artery disease, heart failure or other significant cardiac disorder
  • Cerebrovascular accident within the past 6 months
  • A seated systolic blood pressure above 200 mm Hg
  • Significant renal disease, collagen or vascular disease, or gastrointestinal condition
  • Significant allergy or intolerance to study drug
  • Alcohol or drug abuse
  • Uncontrolled diabetes mellitus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Irbesartan
Irbesartan per os titrated to 300 mg od, 48 weeks
Drug: Irbesartan
Titrated to 300 mg od, 48 weeks.
Other Names:
  • Aprovel
Active Comparator: Atenolol
Atenolol per os titrated to 100 mg od, 48 weeks
Drug: Atenolol
Titrated to 100 mg od, 48 weeks.
Other Names:
  • Tenormin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Left Ventricular Mass Index
Time Frame: Baseline and 48 weeks
Repeated measures multivariate analysis of variance (MANOVA) at time points 0, 12, 24, and 48 weeks. Data are presented as left ventricular mass in gram (g) indexed for body mass index (in m^2).
Baseline and 48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Serious Adverse Events
Time Frame: Treatment period was baseline to 48 weeks
Safety was assessed by non-directed questions, and all observed and volunteered adverse events were recorded at each study visit. Serious adverse events were defined by, and reported according to the regulations of good clinical practice (GCP). none were considered related to the study medication.
Treatment period was baseline to 48 weeks
Left Ventricular Diastolic Function Assessed by the E/A Ratio
Time Frame: Baseline to 48 weeks
Changes in left ventricular diastolic function from baseline to week 48 will be evaluated as the difference in E/A ratio. Conventional pulsed wave Doppler echocardiography was used for recordings of mitral inflow in. The peak of early (E) and late (A) mitral flow velocities were measured, and the E/A-ratio was calculated. Repeated measures MANOVA at time points 0, 12, 24, and 48 weeks. Some echocardiographic recordings at some time point may be of insufficient quality or missing, and the number of observations may not always correspond to the total number of participants at all time points.
Baseline to 48 weeks
Blood Pressure
Time Frame: Baseline to 48 weeks
Difference in Diastolic Blood Pressure. Repeated measures multivariable analysis of variance (MANOVA) at time points 0, 12, 24, and 48 weeks
Baseline to 48 weeks
Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System
Time Frame: Baseline to 48 weeks
Venous plasma concentrations of angiotensin II were measured in order to study the possible associations between the activity of the renin-angiotensin-aldosteone system and changes in left ventricular mass. Further analyses of other components of the renin-angiotensin-aldosterone system and of other hormonal system (e.g. the sympathetic nervous system) have also been performed and published. Repeated measures MANOVA at time points 0, 12, 24, and 48 weeks. Data were log-transformed to avoid skewness before statistical evaluation. However, tabular data are given as mean values with 95% confidence to improve readability.
Baseline to 48 weeks
Effects on Carotid Artery Wall Thickness
Time Frame: Baseline to 48 weeks
Changes in common carotid artery intima-media thickness, assessed by ultrasonography.
Baseline to 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

Bristol-Myers Squibb
Sanofi
Swedish Heart Lung Foundation

Investigators

  • Study Chair: Thomas Kahan, MD, PhD, Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1995

Primary Completion (Actual)

April 1, 1997

Study Completion (Actual)

April 1, 1997

Study Registration Dates

First Submitted

October 17, 2006

First Submitted That Met QC Criteria

October 17, 2006

First Posted (Estimate)

October 18, 2006

Study Record Updates

Last Update Posted (Estimate)

May 5, 2015

Last Update Submitted That Met QC Criteria

May 3, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CV131-052

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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