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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01499134
First received: October 24, 2011
Last updated: March 4, 2014
Last verified: March 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 [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Change in measurement of peak walking time


Secondary Outcome Measures:
  • Walking Impairment Questionnaire [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Change in self-reported walking impairment questionnaire

  • Ankle-brachial index [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Change in measurement of Ankle-brachial index

  • markers of inflammation. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • Claudication Onset Time [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Change in measurement of Claudication onset time


Estimated Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 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 ABI 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

Contacts
Contact: Suzanne Adams, RN MPH 215 955 8848 suzanne.adams@jefferson.edu
Contact: Lisa Pawlowski, RN 215 955 2213 lisa.pawlowski@jefferson.edu

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Suzanne Adams, RN MPH    215-955-8848    suzanne.adams@jefferson.edu   
Contact: Lisa Pawlowski, RN BSN    215 955 2213    lisa.pawlowski@jefferson.edu   
Principal Investigator: Danielle Duffy, MD         
Sub-Investigator: David J Whellan, MD MHS         
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
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypertension
Peripheral Arterial Disease
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Metoprolol
Nebivolol
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on July 29, 2014