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

October 24, 2011
March 4, 2014
August 2011
December 2014   (final data collection date for primary outcome measure)
Peak Walking Time [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Change in measurement of peak walking time
peak walking time (PWT). [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01499134 on ClinicalTrials.gov Archive Site
  • 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
  • The effect of nebivolol vs. metoprolol succinate on claudication onset time (COT). [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • self-reported walking impairment as measured by the modified Walking Impairment Questionnaire (WIQ). [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • change in ankle-brachial index (ABI). [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • markers of inflammation. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure
Effect of Nebivolol Compared With Metoprolol in Hypertensive Patients With Peripheral Arterial Disease

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Peripheral Artery Disease
  • Hypertension
  • 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
  • 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
  • Experimental: nebivolol
    nebivolol 1 to 4 capsules daily
    Intervention: Drug: nebivolol
  • Active Comparator: metoprolol succinate
    metoprolol 1 to 4 capsules daily
    Intervention: Drug: Metoprolol succinate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
December 2015
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Suzanne Adams, RN MPH 215 955 8848 suzanne.adams@jefferson.edu
Contact: Lisa Pawlowski, RN 215 955 2213 lisa.pawlowski@jefferson.edu
United States
 
NCT01499134
11C.18
Yes
Thomas Jefferson University
Thomas Jefferson University
Forest Laboratories
Principal Investigator: Danielle Duffy, MD Thomas Jefferson University
Thomas Jefferson University
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP