Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure (ENCOMPASS)
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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 |
- 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 ]
| Estimated Enrollment: | 40 |
| 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) |
| 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 |
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| 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, 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 | |
| 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: | May 8, 2013 |
| 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 May 16, 2013