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

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01499134
First received: October 24, 2011
Last updated: December 2, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Peripheral Artery Disease
Hypertension
Drug: nebivolol
Drug: Metoprolol succinate
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: Effect of Nebivolol Compared With Metoprolol in Hypertensive Patients With Peripheral Arterial Disease

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Peak Walking Time (PWT) [ Time Frame: Baseline PWT is measured at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline ABI is measured at the time of enrollment and again at the final study visit at 26 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline COT is measured at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks. ] [ Designated as safety issue: No ]
    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.


Enrollment: 17
Study Start Date: August 2011
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nebivolol
nebivolol 1 to 4 capsules daily
Drug: nebivolol
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).
Other Name: Bystolic
Active Comparator: metoprolol succinate
metoprolol 1 to 4 capsules daily
Drug: Metoprolol succinate
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).
Other Name: Toprol XL

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01499134

Locations
United States, Pennsylvania
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Thomas Jefferson University
Forest Laboratories
Investigators
Principal Investigator: Danielle Duffy, MD Thomas Jefferson University
  More Information

No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT01499134     History of Changes
Other Study ID Numbers: 11C.18
Study First Received: October 24, 2011
Results First Received: July 29, 2014
Last Updated: December 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Vascular Diseases
Metoprolol
Metoprolol succinate
Nebivolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-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
Vasodilator Agents

ClinicalTrials.gov processed this record on July 01, 2015