Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure (ENCOMPASS)
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 Artery Disease
Drug: Metoprolol succinate
|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|
- peak walking time (PWT). [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
nebivolol 1 to 4 capsules daily
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
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.
|Contact: Suzanne Adams, RN MPH||215 955 firstname.lastname@example.org|
|Contact: Lisa Pawlowski, RN||215 955 email@example.com|
|United States, Pennsylvania|
|Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Suzanne Adams, RN MPH 215-955-8848 firstname.lastname@example.org|
|Contact: Lisa Pawlowski, RN BSN 215 955 2213 email@example.com|
|Principal Investigator: Danielle Duffy, MD|
|Sub-Investigator: David J Whellan, MD MHS|
|Principal Investigator:||Danielle Duffy, MD||Thomas Jefferson University|