Peripheral Artery DiseasePhase 3ENCOMPASSNCT01499134
Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure
A Phase 3 study testing nebivolol and Metoprolol succinate in people with Peripheral Artery Disease and Hypertension, run by Thomas Jefferson University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Artery Disease, Hypertension
- What is being tested?
- nebivolol and Metoprolol succinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Jun 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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.
Read the 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.
- Conditions
- Peripheral Artery Disease, Hypertension
- Being tested
- nebivolol, Metoprolol succinate
- Medical subject headings
- Peripheral Arterial Disease, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nebivololDrug
Also called Bystolic
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).
Metoprolol succinateDrug
Also called Toprol XL
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).
| Study group | Role | What they receive |
|---|---|---|
| nebivolol | Experimental | nebivolol 1 to 4 capsules daily Receives: Drug: nebivolol |
| metoprolol succinate | Active comparator | metoprolol 1 to 4 capsules daily Receives: Drug: Metoprolol succinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Walking Time (PWT)
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.
Measured: Baseline PWT is measured at the time of enrollment and again at the final study visit at 26 weeks.
Secondary outcomes (7)
Ankle-brachial Index (ABI)
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.
Measured: Baseline ABI is measured at the time of enrollment and again at the final study visit at 26 weeks
Claudication Onset Time (COT)
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.
Measured: Baseline COT is measured at the time of enrollment and again at the final study visit at 26 weeks.
Walking Impairment Questionnaire (WIQ) - Change Calf Pain
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.
Measured: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.
Walking Impairment Questionnaire (WIQ) - Change in Buttock Pain
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.
Measured: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.
Walking Impairment Questionnaire (WIQ) - Change in WIQ Distance Score
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.
Measured: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.
Walking Impairment Questionnaire (WIQ) - Change in WIQ Speed Score
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.
Measured: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.
Walking Impairment Questionnaire (WIQ) - Change in WIQ Stairs Score
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.
Measured: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startAug 2011
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peripheral Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Danielle Duffy, MD, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499134
- Sponsor's protocol ID
- 11C.18
- Acronym
- ENCOMPASS
- Status last verified
- Dec 2014
- First submitted
- 24 Oct 2011
- Last updated
- 17 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Nebivolol Compared With Metoprolol in Hypertensive Patients With Peripheral Arterial Disease
- ClinicalTrials.gov ID
- NCT01499134
- Acronym / sponsor ID
- ENCOMPASS / 11C.18
- Conditions
- Peripheral Artery Disease, Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Aug 2011
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Posted 3 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| nebivolol | Experimental | Drug: nebivololnebivolol 1 to 4 capsules daily |
| metoprolol succinate | Active comparator | Drug: Metoprolol succinatemetoprolol 1 to 4 capsules daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nebivololAlso: BystolicStudy 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). | Drug | nebivolol |
| Metoprolol succinateAlso: Toprol XLStudy 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). | Drug | metoprolol succinate |
Primary outcome
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.
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.
7 secondary outcomes
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
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.
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.
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.
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.
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Danielle Duffy, MD principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing nebivolol and Metoprolol succinate in people with Peripheral Artery Disease and Hypertension, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2014.