Trial Outcomes & Findings for Irbesartan and Atenolol in Hypertensive Heart Disease (NCT NCT00389168)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

115 participants

Primary outcome timeframe

Baseline and 48 weeks

Results posted on

2015-05-05

Participant Flow

Multicenter Swedish study. Patients with primary hypertension and left ventricular (LV) hypertrophy.

All participants received a placebo washout period during 4 weeks at the beginning of the study. One patient of the 115 included was during the course of the study diagnosed with Mb Conn (adrenal tumor causing endocrine secondary hypertension). This patient was excluded from all analyses. Thus, there are 114 patients included in the dataset.

Participant milestones

Participant milestones
Measure	Irbesartan A double blind study with parallel group treatment with irbesartan or atenolol; addition of hydrochlorothiazide (HCTZ) and felodipine when needed to achieve \< 140/90 mm Hg	Atenolol A double blind study with parallel group treatment with irbesartan or atenolol; addition of hydrochlorothiazide (HCTZ) and felodipine when needed to achieve \< 140/90 mm Hg
Overall Study NOT COMPLETED	9	5
Overall Study STARTED	56	58
Overall Study COMPLETED	47	53

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Irbesartan and Atenolol in Hypertensive Heart Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atenolol n=58 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=56 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Total n=114 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	51 Participants n=5 Participants	49 Participants n=7 Participants	100 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Age, Continuous	54 years STANDARD_DEVIATION 10 • n=5 Participants	54 years STANDARD_DEVIATION 8 • n=7 Participants	54 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	36 Participants n=7 Participants	76 Participants n=5 Participants
Region of Enrollment Sweden	58 participants n=5 Participants	56 participants n=7 Participants	114 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 48 weeks

Population: Data on echocardiography is not always available at all time points and for all participants. This is reflected by the number of observations, which sometimes are less than the number of participants.

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).

Outcome measures

Outcome measures
Measure	Atenolol n=50 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=44 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Changes in Left Ventricular Mass Index 12 weeks	-1 g/m^2 Interval -6.0 to 4.0	-9 g/m^2 Interval -15.0 to -6.0
Changes in Left Ventricular Mass Index 24 weeks	-6 g/m^2 Interval -12.0 to 0.0	-14 g/m^2 Interval -22.0 to -6.0
Changes in Left Ventricular Mass Index 48 weeks	-14 g/m^2 Interval -20.0 to 9.0	-26 g/m^2 Interval -34.0 to -18.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atenolol n=58 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=56 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Number of Participants With Serious Adverse Events	5 Participants	5 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atenolol n=50 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=45 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Left Ventricular Diastolic Function Assessed by the E/A Ratio Week 12	0.18 ratio Standard Deviation 0.23	0.10 ratio Standard Deviation 0.22
Left Ventricular Diastolic Function Assessed by the E/A Ratio Week 24	0.16 ratio Standard Deviation 0.28	0.04 ratio Standard Deviation 0.18
Left Ventricular Diastolic Function Assessed by the E/A Ratio Week 48	0.13 ratio Standard Deviation 0.24	0.10 ratio Standard Deviation 0.21

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Atenolol n=53 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=47 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Blood Pressure	-16.3 mm Hg Interval -18.5 to -14.0	-18.8 mm Hg Interval -21.4 to -16.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Atenolol n=53 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=46 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System Weel 12	-1.0 pmol/L Interval -1.4 to -0.5	3.0 pmol/L Interval 1.2 to 4.9
Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System Week 24	-0.8 pmol/L Interval -1.4 to -0.1	3.3 pmol/L Interval 1.8 to 4.7
Changes of Venous Plasma Angiotensin II as a Marker of the Renin-Angiotensin-Aldosterone System Week 48	-0.2 pmol/L Interval -0.9 to 0.4	10.0 pmol/L Interval 5.0 to 15.0

SECONDARY outcome

Timeframe: Baseline to 48 weeks

Changes in common carotid artery intima-media thickness, assessed by ultrasonography.

Outcome measures

Outcome measures
Measure	Atenolol n=56 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Irbesartan n=52 Participants A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Effects on Carotid Artery Wall Thickness	0.03 mm Standard Deviation 0.12	-0.01 mm Standard Deviation 0.10

Adverse Events

Irbesratan

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Atenolol

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Irbesratan n=56 participants at risk A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg	Atenolol n=58 participants at risk A double blind study with parallel group treatment with irbesartan or atenolol; addition of HCTZ and felodipine when needed to achieve \< 140/90 mm Hg
Cardiac disorders inadequate blood pressure reduction	3.6% 2/56 • Number of events 2 • The entire duration of study: that is 4-6 weeks of single-blinded placebo run-in, 48 weeks of double-blinded medication, and 4 weeks following completion of the study. Defied and reported according to study protocol.	0.00% 0/58 • The entire duration of study: that is 4-6 weeks of single-blinded placebo run-in, 48 weeks of double-blinded medication, and 4 weeks following completion of the study. Defied and reported according to study protocol.
Social circumstances events were not documented specifically in the records available	5.4% 3/56 • Number of events 3 • The entire duration of study: that is 4-6 weeks of single-blinded placebo run-in, 48 weeks of double-blinded medication, and 4 weeks following completion of the study. Defied and reported according to study protocol.	8.6% 5/58 • Number of events 5 • The entire duration of study: that is 4-6 weeks of single-blinded placebo run-in, 48 weeks of double-blinded medication, and 4 weeks following completion of the study. Defied and reported according to study protocol.

Other adverse events

Adverse event data not reported

Additional Information

Thomas Kahan, MD

Karolinska Institutet, Stockholm, Sweden

Phone: +46 8 123 568 61

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60