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Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure (ENCOMPASS)

Primary Purpose

Peripheral Artery Disease, Hypertension

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

nebivolol

Metoprolol succinate

About this trial

This is an interventional treatment trial for Peripheral Artery Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men and non-pregnant, non-lactating women 45 years of age or older
Able to give informed consent and complete scheduled visits
Mild-moderate bilateral lower extremity peripheral arterial disease as defined by an ankle-brachial index (ABI measurement of 0.6-0.9. If a subject has baseline claudication symptoms, the symptoms must be stable for the 3 months preceding enrollment.
History of hypertension. Blood pressure at the screening visit must be ≤160/100 mmHg and ≥100/60 mmHg for all subjects. If a subject is currently prescribed beta-blocker therapy, BP at the screening visit must be ≤140/90 mmHg. In addition, heart rate must be ≥55 beats per minute if currently prescribed a beta-blocker and ≤60 beats per minute if not currently prescribed a beta-blocker.
At least moderate risk for CAD.

Exclusion Criteria:

Participation in another clinical trial
Ongoing ischemic (resting) limb pain, or lower extremity ulceration due to arterial insufficiency, or an ABI indicating <0.6 indicating disease potentially requiring revascularization
History of limb or digit amputation due to arterial insufficiency
Revascularization of peripheral vessels within the preceding 6 months
Uncontrolled hypertension as defined by systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg
Contraindication or allergy to beta blocker therapy
History of myocardial infarction , coronary revascularization, or a cerebrovascular event within the preceding 6 months
Class III or IV angina
Current or past history of New York Heart Association (NYHA) class III or IV heart failure
Inability to walk on a treadmill for any reason
Regular use of nitroglycerin or nitrates including oral, transdermal ointment or patch, or sublingual, translingual spray and/or combination agents containing nitrates
Active liver, pulmonary, infectious or inflammatory process
History of malignancy within preceding 5 years (excluding basal or squamous cell skin cancer)
History of any other condition that, in the opinion of the investigators, renders it unsafe for the subject to be enrolled

Sites / Locations

Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

nebivolol

metoprolol succinate

Arm Description

nebivolol 1 to 4 capsules daily

metoprolol 1 to 4 capsules daily

Outcomes

Primary Outcome Measures

Peak Walking Time (PWT)

Change in peak walking time (PWT) is measured in seconds. The PWT is defined as when walking on a treadmill cannot continue due to maximal leg pain, resulting in the discontinuation of the treadmill test.

Secondary Outcome Measures

Ankle-brachial Index (ABI)

Change in measurement of Ankle-brachial index (ABI). The ABI is the ratio of the blood pressure measured in the lower legs to the blood pressure measured in the arms.

Claudication Onset Time (COT)

Change in measurement of claudication onset time (COT). The COT is defined as the time when a patient first experienced pain walking during a treadmill test.

Walking Impairment Questionnaire (WIQ) - Change Calf Pain

Change in calf pain as captured by the Walking Impairment Questionnaire (WIQ). A 5 point Likert scale scoring ranges from 1) No Difficulty, 2) Slight Difficulty, 3) Some Difficulty, 4) Much Difficulty, and 5) Great Difficulty. The scores are determined by dividing the score by the maximum possible score and then multiplying by 100. The score ranges from 0-100 with lower scores indicating greater pain.

Walking Impairment Questionnaire (WIQ) - Change in Buttock Pain

Change in buttock pain as captured by the Walking Impairment Questionnaire (WIQ). A 5 point Likert scale scoring ranges from 1) No Difficulty, 2) Slight Difficulty, 3) Some Difficulty, 4) Much Difficulty, and 5) Great Difficulty. The scores are determined by dividing the score by the maximum possible score and then multiplying by 100. The score ranges from 0-100 with lower scores indicating greater pain.

Walking Impairment Questionnaire (WIQ) - Change in WIQ Distance Score

Change in distance score as captured by the Walking Impairment Questionnaire (WIQ) distance score subscale. The degree of difficulty in the walking of specific distances is ranked on a 0 to 4 Likert scale, in which 0 represents the inability to walk the distance and 4 represents no difficulty. A Likert scale is an ordinal scale of consecutive, equidistant, numerical values (ie, 0 to 4). The distances assessed in the WIQ range from walking indoors around the home to walking 5 blocks (1500 feet). The items on the subscale are weighted according to the difficulty of walking. The distance score is determined by dividing the total weighted score by the greatest possible weighted score and multiplying by 100. Scores range from 0-100.

Walking Impairment Questionnaire (WIQ) - Change in WIQ Speed Score

Change in speed score as captured by the Walking Impairment Questionnaire (WIQ) speed score subscale. In the walking speed component, the degree of difficulty walking is ranked on a 0 to 4 scale where speed is assessed for each of the following speeds: at the following speeds: 1, slowly; 2, average speed; 3, quickly; or 4, running or jogging 1 block. Zero represents the inability to walk the specified speed, and 4 represents no difficulty. The items on the subscale are weighted according to the difficulty of the task. The speed score is determined by dividing the total weighted score by the greatest possible weighted score and multiplying by 100. Scores range from 0-100.

Walking Impairment Questionnaire (WIQ) - Change in WIQ Stairs Score

Change in stairs score as captured by the Walking Impairment Questionnaire (WIQ) stairs subscale. This scale item asks the subject to describe the degree of difficulty climbing one, two, or three flights of stairs in the past week. A flight of stairs is defined as 14 steps. A 5 point Likert scale scoring ranges from 1) No Difficulty, 2) Slight Difficulty, 3) Some Difficulty, 4) Much Difficulty, 5) Unable to Do, or 6) Didn Do for Other Reasons. The items on the subscale are weighted according to the difficulty of the task. The stairs score is determined by dividing the total weighted score by the greatest possible weighted score and multiplying by 100. Scores range from 0-100.

Full Information

NCT ID

NCT01499134

First Posted

October 24, 2011

Last Updated

December 2, 2014

Sponsor

Thomas Jefferson University

Collaborators

Forest Laboratories

1. Study Identification

Unique Protocol Identification Number

NCT01499134

Brief Title

Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure

Acronym

ENCOMPASS

Official Title

Effect of Nebivolol Compared With Metoprolol in Hypertensive Patients With Peripheral Arterial Disease

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

August 2011 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Thomas Jefferson University

Collaborators

Forest Laboratories

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a 26-week, prospective double-blind, randomized pilot trial of nebivolol versus an active control, metoprolol succinate, in patients with established lower-extremity peripheral artery disease, hypertension, and at least moderate risk for coronary artery disease.

Detailed Description

Peripheral arterial disease (PAD) affects up to an estimated 16-29% of men and women over age 50, and is associated with increased cardiovascular morbidity and mortality. Beta-blockers have been shown to reduce the risk of myocardial infarction and death in patients with coronary artery disease (CAD) and are indicated for the treatment of hypertension in patients with PAD. However, there is a theoretical risk that antihypertensive therapy may decrease limb perfusion pressure and therefore exacerbate symptoms of claudication or limb ischemia. Patients with CAD and concomitant PAD are less likely to be prescribed beta-blockers, even though most patients are able to tolerate antihypertensive therapy without worsening of symptoms. The third generation beta-blocker, nebivolol, has vasodilating properties in addition to beta-adrenergic blockade. This vasodilatory effect is mediated through the L-arginine-nitric oxide-dependent pathway. Nitric oxide is a critical modulator of vascular disease with effects that lead to vasodilatation, endothelial regeneration, inhibition of leukocyte chemotaxis and inhibition of platelet adhesion. This combination of beta-blockade and nitric oxide-dependent vasodilation may enhance effectiveness and tolerability of nebivolol versus other beta-blockers in patients with hypertension, CAD or high-risk state, and PAD. This study will be a pilot comparative effectiveness study to examine the effect of nebivolol versus metoprolol succinate in patients with lower-extremity PAD and at least moderate risk for CAD on PAD symptoms as measured by both functional and quality of life measures.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral Artery Disease, Hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

nebivolol

Arm Type

Experimental

Arm Description

nebivolol 1 to 4 capsules daily

Arm Title

metoprolol succinate

Arm Type

Active Comparator

Arm Description

metoprolol 1 to 4 capsules daily

Intervention Type

Drug

Intervention Name(s)

nebivolol

Other Intervention Name(s)

Bystolic

Intervention Description

Study medication will initially be dispensed as one capsule daily and the dose will be titrated at the study visits. Nebivolol is approved for hypertension treatment at a dose of 5-40 mg daily. Based on the study titration schedule, the maximum doses used will be 20 mg of nebivolol (each maximum dose being contained in 4 capsules for daily dosing).

Intervention Type

Drug

Intervention Name(s)

Metoprolol succinate

Other Intervention Name(s)

Toprol XL

Intervention Description

Study medication will initially be dispensed as one capsule daily and the dose will be titrated at study visits. Metoprolol succinate at 25-400 mg daily. Based on the study titration schedule, the maximum dose used will be 200 mg of metoprolol succinate (each maximum dose being contained in 4 capsules for daily dosing).

Primary Outcome Measure Information:

Title

Peak Walking Time (PWT)

Description

Time Frame

Baseline PWT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Secondary Outcome Measure Information:

Title

Ankle-brachial Index (ABI)

Description

Change in measurement of Ankle-brachial index (ABI). The ABI is the ratio of the blood pressure measured in the lower legs to the blood pressure measured in the arms.

Time Frame

Baseline ABI is measured at the time of enrollment and again at the final study visit at 26 weeks

Title

Claudication Onset Time (COT)

Description

Change in measurement of claudication onset time (COT). The COT is defined as the time when a patient first experienced pain walking during a treadmill test.

Time Frame

Baseline COT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Title

Walking Impairment Questionnaire (WIQ) - Change Calf Pain

Description

Time Frame