Irbesartan and Atenolol in Hypertensive Heart Disease (SILVHIA)

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Sanofi
Swedish Heart Lung Foundation
Information provided by (Responsible Party):
Thomas Kahan, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT00389168
First received: October 17, 2006
Last updated: May 3, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Hypertension
Drug: Irbesartan
Drug: Atenolol
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind Evaluation of the Effects of Irbesartan and Atenolol on Cardiovascular Structure and Function in Subjects With Hypertension and Left Ventricular Hypertrophy

Resource links provided by NLM:


Further study details as provided by Karolinska Institutet:

Primary Outcome Measures:
  • Changes in Left Ventricular Mass Index [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Number of Participants With Serious Adverse Events [ Time Frame: Treatment period was baseline to 48 weeks ] [ Designated as safety issue: No ]
    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.

  • Left Ventricular Diastolic Function Assessed by the E/A Ratio [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    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.

  • Blood Pressure [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    Difference in Diastolic Blood Pressure. Repeated measures multivariable analysis of variance (MANOVA) at time points 0, 12, 24, and 48 weeks

  • Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    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.

  • Effects on Carotid Artery Wall Thickness [ Time Frame: Baseline to 48 weeks ] [ Designated as safety issue: No ]
    Changes in common carotid artery intima-media thickness, assessed by ultrasonography.


Enrollment: 115
Study Start Date: April 1995
Study Completion Date: April 1997
Primary Completion Date: April 1997 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Irbesartan
Irbesartan per os titrated to 300 mg od, 48 weeks
Drug: Irbesartan
Titrated to 300 mg od, 48 weeks.
Other Name: Aprovel
Active Comparator: Atenolol
Atenolol per os titrated to 100 mg od, 48 weeks
Drug: Atenolol
Titrated to 100 mg od, 48 weeks.
Other Name: Tenormin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389168

Locations
Sweden
Karolinska Institutet, Daprtment of Clinical Sciences, Danderyd Hospital, Cardiovascular Research Laboratory
Stockholm, Sweden, SE-182 88
Sponsors and Collaborators
Karolinska Institutet
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
  More Information

Publications:

Responsible Party: Thomas Kahan, Professor, Principal investigator and Study Chair, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT00389168     History of Changes
Other Study ID Numbers: CV131-052
Study First Received: October 17, 2006
Results First Received: August 19, 2012
Last Updated: May 3, 2015
Health Authority: Sweden: Regional Ethical Review Board

Keywords provided by Karolinska Institutet:
Hypertension
Cardiac hypertrophy
Angiotensin
Human

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Atenolol
Irbesartan
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Autonomic Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympatholytics
Therapeutic Uses

ClinicalTrials.gov processed this record on June 30, 2015