Trial Outcomes & Findings for Comparison of 2 Beta Blocker Drugs on Peripheral Arterial Disease in Patients With High Blood Pressure (NCT NCT01499134)

Last Updated: 2014-12-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

17 participants

Primary outcome timeframe

Baseline PWT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Results posted on

2014-12-17

Participant Flow

Participant milestones

Participant milestones
Measure	Nebivolol nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate metoprolol 1 to 4 capsules daily 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).
Overall Study STARTED	9	8
Overall Study COMPLETED	9	7
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Nebivolol nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate metoprolol 1 to 4 capsules daily 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).
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=8 Participants metoprolol 1 to 4 capsules daily 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).	Total n=17 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 8 • n=5 Participants	65 years STANDARD_DEVIATION 8 • n=7 Participants	66 years STANDARD_DEVIATION 8 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline PWT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Population: One patient in the metoprolol succinate group withdrew consent prior to the end of the study, therefore, only 7 participants are included in the analysis for this group.

Outcome measures

Outcome measures
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=7 Participants metoprolol 1 to 4 capsules daily 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).
Peak Walking Time (PWT)	110.4 seconds Standard Deviation 89.7	-19.4 seconds Standard Deviation 110.8

SECONDARY outcome

Timeframe: Baseline ABI is measured at the time of enrollment and again at the final study visit at 26 weeks

Population: One patient in the metoprolol succinate group withdrew consent prior to the end of the study, therefore, only 7 participants are included in the analysis for this group.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=7 Participants metoprolol 1 to 4 capsules daily 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).
Ankle-brachial Index (ABI)	0.03 Ankle-Brachial Index Standard Deviation 0.14	0.06 Ankle-Brachial Index Standard Deviation 0.11

SECONDARY outcome

Timeframe: Baseline COT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Population: Final measurements of COT in the metoprolol succinate group excludes one subject who did not experience claudication while walking during the treadmill test, and one subject who withdrew consent prior to the end of the study, therefore, only 6 participants are included in the analysis for this group.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=6 Participants metoprolol 1 to 4 capsules daily 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).
Claudication Onset Time (COT)	155.7 seconds Standard Deviation 217.5	148.7 seconds Standard Deviation 173.1

SECONDARY outcome

Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Population: One patient in the metoprolol succinate group withdrew consent prior to the end of the study, therefore, only 7 participants are included in the analysis for this group.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=7 Participants metoprolol 1 to 4 capsules daily 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).
Walking Impairment Questionnaire (WIQ) - Change Calf Pain	25 units on a scale Standard Deviation 28	10.7 units on a scale Standard Deviation 40.5

SECONDARY outcome

Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Population: One patient in the metoprolol succinate group withdrew consent prior to the end of the study, therefore, only 7 participants are included in the analysis for this group.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=7 Participants metoprolol 1 to 4 capsules daily 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).
Walking Impairment Questionnaire (WIQ) - Change in Buttock Pain	-8.3 units on a scale Standard Deviation 12.5	14.3 units on a scale Standard Deviation 19.7

SECONDARY outcome

Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Population: One patient in the metoprolol succinate group withdrew consent prior to the end of the study, therefore, only 7 participants are included in the analysis for this group.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=9 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=5 Participants metoprolol 1 to 4 capsules daily 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).
Walking Impairment Questionnaire (WIQ) - Change in WIQ Distance Score	13.52 units on a scale Standard Deviation 27.37	28.28 units on a scale Standard Deviation 31.18

SECONDARY outcome

Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Population: One patient in the metoprolol succinate group withdrew consent prior to the end of the study, therefore, only 7 participants are included in the analysis for this group. One patient in the nebivolol group failed to complete the items in the WIQ speed score subscale, therefore, only 8 patients were included in the analysis for this outcome.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=8 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=7 Participants metoprolol 1 to 4 capsules daily 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).
Walking Impairment Questionnaire (WIQ) - Change in WIQ Speed Score	21.88 units on a scale Standard Deviation 30.08	-6.83 units on a scale Standard Deviation 35.34

SECONDARY outcome

Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Population: Four people in the nebivolol group and 1 person in the metoprolol group did not complete the items in the "Stairs" WIQ subscale therefore they were excluded from the analysis. One person in the metoprolol succinate group withdrew consent before the end of the study so they were also excluded from the final analysis.

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.

Outcome measures

Outcome measures
Measure	Nebivolol n=5 Participants nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=6 Participants metoprolol 1 to 4 capsules daily 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).
Walking Impairment Questionnaire (WIQ) - Change in WIQ Stairs Score	21.67 units on a scale Standard Deviation 37.20	24.31 units on a scale Standard Deviation 38.77

Adverse Events

Nebivolol

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Metoprolol Succinate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nebivolol n=9 participants at risk nebivolol 1 to 4 capsules daily 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).	Metoprolol Succinate n=8 participants at risk metoprolol 1 to 4 capsules daily 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).
Blood and lymphatic system disorders Decrease in hemoglobin	11.1% 1/9 • Number of events 1 • 6 months	0.00% 0/8 • 6 months
Vascular disorders Peripheral stent placed	11.1% 1/9 • Number of events 1 • 6 months	0.00% 0/8 • 6 months

Other adverse events

Adverse event data not reported

Additional Information

Danielle Duffy MD

Thomas Jefferson University

Phone: 215 955 5050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place