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

October 17, 2006
May 3, 2015
April 1995
April 1997   (final data collection date for primary outcome measure)
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).
Safety and tolerability of irbesartan compared to atenolol
Complete list of historical versions of study NCT00389168 on ClinicalTrials.gov Archive Site
  • 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.
  • Compare changes in left ventricular mass
  • Evaluate changes in diastolic function
  • Compare changes in blood pressure
  • Examine the relationship between changes in left ventricular mass and sympathetic influence, and influence of the renin-angiotensin-aldosterone system
  • Compare the effects on carotid artery wall thickness
Not Provided
Not Provided
 
Irbesartan and Atenolol in Hypertensive Heart Disease
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.

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.
Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypertension
  • Drug: Irbesartan
    Titrated to 300 mg od, 48 weeks.
    Other Name: Aprovel
  • Drug: Atenolol
    Titrated to 100 mg od, 48 weeks.
    Other Name: Tenormin
  • Experimental: Irbesartan
    Irbesartan per os titrated to 300 mg od, 48 weeks
    Intervention: Drug: Irbesartan
  • Active Comparator: Atenolol
    Atenolol per os titrated to 100 mg od, 48 weeks
    Intervention: Drug: Atenolol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
115
April 1997
April 1997   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
Yes
Contact information is only displayed when the study is recruiting subjects
Sweden
 
NCT00389168
CV131-052
No
Not Provided
Not Provided
Thomas Kahan, Karolinska Institutet
Karolinska Institutet
  • Bristol-Myers Squibb
  • Sanofi
  • Swedish Heart Lung Foundation
Study Chair: Thomas Kahan, MD, PhD Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm, Sweden
Karolinska Institutet
May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP