EFFORT: Safety Study to Lower the Risk of Heart Failure is Also Effective in Reducing Stiffness of the Arteries

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00829296
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 70
• Location: 1
• Arms: 2
• Duration (Months): 51
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The study is being done to see if a drug shown to lower the risk of heart failure is also effective in reducing the stiffness of the arteries.

Condition or Disease	Intervention/Treatment	Phase
Hypertension; Diabetes	Drug: nebivolol; Drug: Metoprolol	Phase 2/Phase 3

Detailed Description

To determine the effect of nebivolol versus metoprolol in Type 2 hypertensive diabetic patients on systolic blood pressure and diastolic blood pressure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: The Effects of Nebivolol on Aortic Impedance Parameters in Type 2 Diabetics
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nebivolol Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached	Drug: nebivolol; Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached; Other Names: bystolic
Active Comparator: Metoprolol Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached	Drug: Metoprolol; Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached; Other Names: lopressor

Outcome Measures

Primary Outcome Measures

1. Change in Central Systolic Blood Pressure (SBP) [Baseline and 26 Weeks]

   Changes in aortic impedance in patients on nebivolol vs. metoprolol succinate in Type 2 hypertensive diabetic patients as measured by the change from baseline in central systolic blood pressure.

Secondary Outcome Measures

1. Change in Pulse Wave Velocity (PWV) [Baseline and 26 Weeks]

   To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse wave velocity.

2. Change in Augmentation Index [Baseline and 26 Weeks]

   Augmentation index is defined as the percentage of the central pulse pressure which is attributed to the reflected pulse wave and, therefore, reflects the degree to which central arterial pressure is augmented by wave reflection.

3. Change in Pulse Pressure Amplification [Baseline and 26 Weeks]

   To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse pressure amplification (central pulse pressure /brachial pulse pressure).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Established Type 2 diabetic not treated with insulin

• Stage 1 hypertensives blood pressure > 130/80 mmHg and < 160/100 mmHg

• BMI < 35

• Hemoglobin A1C < 8.5

• Must be postmenopausal or taking some form of birth control of surgically sterile

Exclusion Criteria:

• Acute myocardial infarction, unstable angina, stroke or TIA within the past year.

• Active angina in the last three months

• Diabetes requiring treatment with insulin

• Severe asthma

• Female who are pregnant, planning to be pregnant during the study period, lactating or women of childbearing potential who are not using a medically approved method of contraception

• Recent history of substance or alcohol abuse .

• Uncontrolled hypertension systolic blood pressure >160mmHg or diastolic blood pressure

100 mmHg

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago
• Forest Laboratories

Investigators

• Principal Investigator: George Bakris, M.D., University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00829296
• Other Study ID Numbers: 16310B (EFFORT trial); NCT01059916
• First Posted: Jan 27, 2009
• Last Update Posted: Feb 5, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by University of Chicago: diabetes; hypertension; aortic impedance
• Additional relevant MeSH terms: Hypertension; Metoprolol; Nebivolol

Study Results

Participant Flow

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Period Title: Overall Study
STARTED	34	36
COMPLETED	29	32
NOT COMPLETED	5	4

Baseline Characteristics

Arm/Group Title	Nebivolol	Metoprolol	Total
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol	Total of all reporting groups
Overall Participants	34	36	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.0 (6.9)	64.1 (6.1)	64.5 (6.4)
Sex: Female, Male (Count of Participants)
Female	23 67.6%	27 75%	50 71.4%
Male	11 32.4%	9 25%	20 28.6%

Outcome Measures

1. Primary Outcome

Title	Change in Central Systolic Blood Pressure (SBP)
Description	Changes in aortic impedance in patients on nebivolol vs. metoprolol succinate in Type 2 hypertensive diabetic patients as measured by the change from baseline in central systolic blood pressure.
Time Frame	Baseline and 26 Weeks

Outcome Measure Data

Analysis Population Description

Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Measure Participants	29	32
Aortic Systolic Blood Pressure at Baseline	125.3 (8.0)	127.8 (8.8)
Aortic Systolic Blood Pressure at 26 Weeks	121.6 (8.2)	123.8 (11.1)

2. Secondary Outcome

Title	Change in Pulse Wave Velocity (PWV)
Description	To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse wave velocity.
Time Frame	Baseline and 26 Weeks

Outcome Measure Data

Analysis Population Description

Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Measure Participants	29	32
Pulse wave velocity at Baseline	6.48 (0.8)	6.52 (1.2)
Pulse wave velocity at 26 Weeks	6.3 (0.9)	6.4 (1.3)

3. Secondary Outcome

Title	Change in Augmentation Index
Description	Augmentation index is defined as the percentage of the central pulse pressure which is attributed to the reflected pulse wave and, therefore, reflects the degree to which central arterial pressure is augmented by wave reflection.
Time Frame	Baseline and 26 Weeks

Outcome Measure Data

Analysis Population Description

Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Measure Participants	29	32
Augmentation index at Baseline	22.0 (7.1)	26.2 (8.3)
Augmentation index at 26 Weeks	22.1 (7.4)	24.6 (6.7)

4. Secondary Outcome

Title	Change in Pulse Pressure Amplification
Description	To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse pressure amplification (central pulse pressure /brachial pulse pressure).
Time Frame	Baseline and 26 Weeks

Outcome Measure Data

Analysis Population Description

Nine patients (4 in the Metoprolol and 5 in the Nebivolol group) discontinued the study medications early in the 26-week follow-up and did not undergo final assessment. Given that our interest was on efficacy, thus, results were reported only on those 61 patients (32 in the Metoprolol and 29 in the Nebivolol group) who completed the study.

Arm/Group Title	Nebivolol	Metoprolol
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol	Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
Measure Participants	29	32
Pulse pressure amplification at Baseline	0.77 (0.08)	0.79 (0.09)
Pulse pressure amplification at 26 Weeks	0.83 (0.09)	0.85 (0.12)

Adverse Events

Arm/Group Title	Nebivolol		Metoprolol
Arm/Group Description	Starting at dose of 5 mg daily titrated up to max of 40 mg until target BP of 130/80 is reached nebivolol		Starting at 50 mg daily dose is titrated to max 200 mg until target BP of 130/80 is reached Metoprolol
All Cause Mortality
	Nebivolol		Metoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Nebivolol		Metoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Nebivolol		Metoprolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/34 (23.5%)		9/36 (25%)
Gastrointestinal disorders
Diarrhea	4/34 (11.8%)		2/36 (5.6%)
General disorders
Fatigue	2/34 (5.9%)		6/36 (16.7%)
Nervous system disorders
Dizziness	2/34 (5.9%)		1/36 (2.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.