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Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

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ClinicalTrials.gov Identifier: NCT02587351
Recruitment Status : Terminated (Futility)
First Posted : October 27, 2015
Results First Posted : January 25, 2021
Last Update Posted : January 25, 2021
Sponsor:
Collaborators:
United States Department of Defense
University of Alabama at Birmingham
Information provided by (Responsible Party):
University of Minnesota

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: Metoprolol succinate
Other: Placebo
Enrollment 532
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Period Title: Overall Study
Started 268 264
Completed 268 264
Not Completed 0 0
Arm/Group Title Metoprolol Succinate Placebo Total
Hide Arm/Group Description

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Total of all reporting groups
Overall Number of Baseline Participants 268 264 532
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 268 participants 264 participants 532 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
122
  45.5%
125
  47.3%
247
  46.4%
>=65 years
146
  54.5%
139
  52.7%
285
  53.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 268 participants 264 participants 532 participants
65.2  (7.6) 64.8  (7.9) 65.0  (7.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 268 participants 264 participants 532 participants
Female
124
  46.3%
123
  46.6%
247
  46.4%
Male
144
  53.7%
141
  53.4%
285
  53.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 268 participants 264 participants 532 participants
White
178
  66.4%
194
  73.5%
372
  69.9%
Black
83
  31.0%
60
  22.7%
143
  26.9%
Other
7
   2.6%
10
   3.8%
17
   3.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 268 participants 264 participants 532 participants
268
 100.0%
264
 100.0%
532
 100.0%
FEV1 after bronchodilation - % of predicted value  
Mean (Standard Deviation)
Unit of measure:  % of predicted value
Number Analyzed 268 participants 264 participants 532 participants
41.3  (16.3) 40.8  (16.2) 41.1  (16.3)
FEV1:FVC ratio - %  
Mean (Standard Deviation)
Unit of measure:  Ratio %
Number Analyzed 268 participants 264 participants 532 participants
44.2  (11.7) 45.2  (21.6) 44.7  (17.3)
Smoking history No. of pack-yr  
Mean (Standard Deviation)
Unit of measure:  Pack-years
Number Analyzed 268 participants 264 participants 532 participants
50.7  (28.7) 49.5  (29.6) 50.1  (29.1)
Systolic Blood pressure - mm Hg  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 268 participants 264 participants 532 participants
128.4  (16.5) 130.6  (15.9) 129.5  (16.2)
Diastolic Blood pressure - mm Hg  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 268 participants 264 participants 532 participants
77.2  (9.2) 76.8  (9.1) 77.0  (9.1)
1.Primary Outcome
Title Time to First Occurrence of an Acute COPS Exacerbation
Hide Description Acute exacerbations are defined as a "complex of respiratory symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnea, or chest tightness requiring treatment with antibiotics and/or systemic steroids for at least three days".
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Mean (95% Confidence Interval)
Unit of Measure: days
202
(162 to 282)
222
(189 to 295)
2.Secondary Outcome
Title Number of Acute Exacerbations of COPD
Hide Description Number of acute exacerbations of COPD - rate per person-year
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Mean (95% Confidence Interval)
Unit of Measure: no. of events/person-yr
1.40
(1.21 to 1.61)
1.33
(1.15 to 1.54)
3.Secondary Outcome
Title Number of Emergency Department Visits Resulting From Acute Exacerbations of COPD
Hide Description Number of Emergency Department visits resulting from acute exacerbations of COPD - rate
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Mean (95% Confidence Interval)
Unit of Measure: events per person-year
0.17
(0.11 to 0.25)
0.18
(0.12 to 0.26)
4.Secondary Outcome
Title Number of Hospital Admissions Resulting From Acute Exacerbations of COPD
Hide Description Number of hospital admissions resulting from acute exacerbations of COPD - rate
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Mean (95% Confidence Interval)
Unit of Measure: events per person-year
0.66
(0.47 to 0.86)
0.42
(0.30 to 0.55)
5.Secondary Outcome
Title Hospital Days Resulting From Acute Exacerbations of COPD
Hide Description Number of hospital days resulting from acute exacerbations of COPD reported as negative binomial estimates of mean hospital days per patient year.
Time Frame 14 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Mean (95% Confidence Interval)
Unit of Measure: hospital days
3.09
(2.05 to 4.64)
0.96
(0.62 to 1.48)
6.Secondary Outcome
Title Major Adverse Cardiovascular Events
Hide Description Major adverse cardiovascular events (MACE), percutaneous coronary intervention or coronary artery bypass grafting. MACE defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Measure Type: Count of Participants
Unit of Measure: Participants
Myocardial Infarction
2
   0.7%
1
   0.4%
Heart Failure
2
   0.7%
3
   1.1%
Stroke
1
   0.4%
1
   0.4%
Sudden Cardiac Death
0
   0.0%
1
   0.4%
7.Secondary Outcome
Title All-cause Mortality
Hide Description All-cause mortality count
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Measure Type: Count of Participants
Unit of Measure: Participants
11
   4.1%
5
   1.9%
8.Secondary Outcome
Title Incidence of Presumed Metoprolol-related Side-effects
Hide Description New or worsened (Neural: depression, headache, syncope, seizures, somnolence, memory loss, loss of sexual desire or erectile dysfunction, and fatigue; Hypersensitivity: rash, pruritus, tongue or facial swelling; Gastrointestinal: diarrhea, vomiting, nausea or constipation; Cardiovascular: bradycardia and hypotension as discussed below; Respiratory: bronchospasm and changes in lung function as discussed below).
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Measure Type: Count of Participants
Unit of Measure: Participants
Depression
28
  10.4%
39
  14.8%
Headache
71
  26.5%
78
  29.5%
Fainting
4
   1.5%
8
   3.0%
Daytime Sleepiness
58
  21.6%
70
  26.5%
Memory Loss
20
   7.5%
21
   8.0%
Loss of sexual desire or erectile dysfunction
10
   3.7%
6
   2.3%
Lack of energy
91
  34.0%
77
  29.2%
Rash
17
   6.3%
21
   8.0%
Itching
11
   4.1%
18
   6.8%
Tongue or facial swelling
7
   2.6%
5
   1.9%
Vomiting
11
   4.1%
18
   6.8%
Nausea
45
  16.8%
42
  15.9%
Constipation
30
  11.2%
32
  12.1%
Wheezing
88
  32.8%
79
  29.9%
Shortness of breath
115
  42.9%
112
  42.4%
Chest tightness
81
  30.2%
80
  30.3%
Heart skipping or irregular beats
16
   6.0%
15
   5.7%
Dizziness/light headedness
74
  27.6%
64
  24.2%
9.Secondary Outcome
Title Modified Medical Research Council Dyspnea Scale (MMRC)
Hide Description Modified Medical Research Council Dyspnea Scale (MMRC) change from baseline to visit day 336. The MMRC scale is a five-point scale originally published in 1959 that considers certain activities, such as walking or climbing stairs, which provoke breathlessness. Scale from 0 to 4 with lower scores indicating less breathlessness.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with data at baseline and visit day 336
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 207 201
Median (Inter-Quartile Range)
Unit of Measure: score on a scale
2.0
(1.0 to 3.0)
2.0
(1.0 to 3.0)
10.Secondary Outcome
Title Forced Expiratory Volume in 1 Second (FEV1)
Hide Description Change in FEV1 % Predicted from baseline to visit day 336 as assessed by spirometry
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with data at baseline and visit day 336
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 193 197
Mean (95% Confidence Interval)
Unit of Measure: percentage of predicted
-2.24
(-3.28 to -1.20)
-1.46
(-2.50 to -0.42)
11.Secondary Outcome
Title Exercise Capacity as Assessed by the 6 Minute Walk Distance (6MWD)
Hide Description 6MWD change from baseline to visit day 336. The 6MWD has been used as a simple tool to assess overall exercise tolerance in patients with chronic cardiopulmonary disease including COPD.
Time Frame Baseline, 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with data at baseline and visit day 336
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 174 166
Mean (95% Confidence Interval)
Unit of Measure: meters
-17.64
(-28.75 to -6.53)
-11.87
(-23.21 to -0.54)
12.Secondary Outcome
Title Markers of Systemic Inflammation
Hide Description Fibrinogen: assessed at screening/randomization and at conclusion of the study to determine if beta-blockade impacts levels of systemic inflammation that portend overall cardiac risk.
Time Frame Baseline, 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Mean (Standard Deviation)
Unit of Measure: mg/dL
Fibrinogen baseline 384.8  (94.6) 378.2  (91.9)
Fibrinogen Visit 336 392.5  (90.5) 386.0  (110.0)
13.Secondary Outcome
Title St. George's Respiratory Questionnaire (SGRQ)
Hide Description SGRQ change from baseline to visit day 336. The SGRQ total score change from baseline. SGRQ is a respiratory specific health status questionnaire with scores ranging from 0 to 100. The lower score indicates a better health status.
Time Frame Baseline, 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with data at baseline and visit day 336
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 203 200
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
0.52
(-1.01 to 2.04)
-0.25
(-1.79 to 1.28)
14.Secondary Outcome
Title COPD Assessment Test (CAT)
Hide Description COPD Assessment Test (CAT) change from baseline. The CAT is a simple, eight item, health status instrument for patients with COPD that provides a score of 0-40. Lower scores denote better health status.
Time Frame Baseline, 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with data at baseline and visit day 336
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 206 200
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
0.88
(0.07 to 1.69)
-0.59
(-1.41 to 0.23)
15.Secondary Outcome
Title San Diego Shortness of Breath Questionnaire (SOBQ)
Hide Description San Diego Shortness of Breath Questionnaire (SOBQ) change from baseline. A 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. Each item has a 6-point scale (0 = "not at all" to 5 = "maximal or unable to do because of breathlessness").
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with data at baseline and visit day 336
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 204 199
Mean (95% Confidence Interval)
Unit of Measure: score on a scale
0.52
(-1.01 to 2.04)
-0.25
(-1.79 to 1.28)
16.Secondary Outcome
Title Acute Exacerbations of COPD and MACE
Hide Description MACE defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 268 264
Measure Type: Count of Participants
Unit of Measure: Participants
Myocardial Infarction
2
   0.7%
1
   0.4%
Heart Failure
2
   0.7%
3
   1.1%
Stroke
1
   0.4%
1
   0.4%
Sudden cardiac death
0
   0.0%
1
   0.4%
COPD Exacerbation (Serious)
55
  20.5%
32
  12.1%
17.Secondary Outcome
Title Short Form Health Survey (SF-36) Physical Function Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. 8 multi-item scales with higher score indicating better health state. The Physical Functioning scale is 10 items assessing the extent to which health limits physical activities such as self-care, walking, climbing stairs, bending lifting, and moderate and vigorous activities transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
30.0
(15.0 to 50.0)
30.0
(15.0 to 45.0)
Day 112 visit
30.0
(15.0 to 55.0)
30.0
(15.0 to 50.0)
Day 336 Visit
30.0
(15.0 to 50.0)
35.0
(15.0 to 50.0)
18.Secondary Outcome
Title Short Form Health Survey (SF-36) Role Functioning - Physical Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The Role Functioning - Physical Scale contains 4 items assessing the extent to which physical health interferes with work or other daily activities, including accomplished less than wanted, limitations in the kind of activities. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
25.0
(0.0 to 50.0)
25.0
(0.0 to 56.2)
Day 112 visit
25.0
(0.0 to 75.0)
25.0
(0.0 to 75.0)
Day 336 Visit
12.5
(0.0 to 75.0)
12.5
(0.0 to 50.0)
19.Secondary Outcome
Title Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The Role Functioning - Emotional Scale includes 3 items assessing extent to which emotional problems interfere with work or other daily activities. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
100.0
(0.0 to 100.0)
66.7
(0.0 to 100.0)
Day 112 visit
66.7
(0.0 to 100.0)
66.7
(0.0 to 100.0)
Day 336 Visit
66.7
(0.0 to 100.0)
66.7
(0.0 to 100.0)
20.Secondary Outcome
Title Short Form Health Survey (SF-36) Energy/Fatigue Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The Energy/Fatigue Scale includes 4 items. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
50.0
(35.0 to 60.0)
50.0
(35.0 to 60.0)
Day 112 visit
50.0
(35.0 to 60.0)
45.0
(30.0 to 60.0)
Day 336 Visit
50.0
(35.0 to 60.0)
45.0
(30.0 to 55.0)
21.Secondary Outcome
Title Short Form Health Survey (SF-36) Emotional Well-being Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The Emotional Well-being Scale includes 5 items assessing emotional wellbeing. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
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Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
76.0
(60.0 to 84.0)
72.0
(56.0 to 84.0)
Day 112 visit
76.0
(60.0 to 88.0)
72.0
(56.0 to 84.0)
Day 336 Visit
76.0
(60.0 to 88.0)
72.0
(56.0 to 84.0)
22.Secondary Outcome
Title Short Form Health Survey (SF-36) Social Functioning Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The Social Functioning Scale includes 2 items assessing extent to which physical health or emotional problems interfere with normal social activities. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
62.5
(50.0 to 87.5)
62.5
(50.0 to 87.5)
Day 112 visit
62.5
(50.0 to 87.5)
62.5
(50.0 to 87.5)
Day 336 Visit
75.0
(50.0 to 87.5)
62.5
(37.5 to 87.5)
23.Secondary Outcome
Title Short Form Health Survey (SF-36) Bodily Pain Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The Bodily Pain Scale includes 2 items assessing the intensity of pain and effect of pain on normal work, both inside and outside the house. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
67.5
(45.0 to 90.0)
67.5
(45.0 to 90.0)
Day 112 visit
67.5
(45.0 to 90.0)
67.5
(45.0 to 90.0)
Day 336 Visit
57.5
(35.0 to 90.0)
57.5
(42.5 to 87.5)
24.Secondary Outcome
Title Short Form Health Survey (SF-36) General Health Scale
Hide Description Short Form Health Survey (SF-36) is a generic tool to assess overall health status and allows comparison between different diseases. Includes 8 multi-item scales with higher score indicating better health state. The General Health Scale includes 4 items assessing personal evaluations of health. Items are transformed to a score with a range of 0-100.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with SF-36 data available
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description:

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

Overall Number of Participants Analyzed 265 262
Median (Inter-Quartile Range)
Unit of Measure: Units on a scale
Baseline
40.0
(25.0 to 55.0)
40.0
(25.0 to 55.0)
Day 112 visit
40.0
(25.0 to 55.0)
35.0
(25.0 to 55.0)
Day 336 Visit
40.0
(25.0 to 55.0)
35.0
(25.0 to 50.0)
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Metoprolol Succinate Placebo
Hide Arm/Group Description

Metoprolol succinate extended release tablets (50 mg) starting dose followed by a dose titration procedure which will result in a final dose of 25mg (1/2 of one tablet daily), 50 mg, or 100 mg (two tablets daily).

Metoprolol succinate: Extended release Metoprolol succinate

Matched placebo

Placebo: Matching placebo

All-Cause Mortality
Metoprolol Succinate Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   11/268 (4.10%)      5/264 (1.89%)    
Hide Serious Adverse Events
Metoprolol Succinate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   86/268 (32.09%)      59/264 (22.35%)    
Cardiac disorders     
Myocardial infarction  1  2/268 (0.75%)  2 1/264 (0.38%)  1
Heart failure  1  2/268 (0.75%)  2 3/264 (1.14%)  3
Stroke  1  1/268 (0.37%)  1 1/264 (0.38%)  2
Arrhythmias  1  2/268 (0.75%)  2 2/264 (0.76%)  2
Hypotension  1  0/268 (0.00%)  0 1/264 (0.38%)  1
Other Cardiovascular  1  1/268 (0.37%)  1 1/264 (0.38%)  1
Chest Pain, not otherwise specified  1  1/268 (0.37%)  1 1/264 (0.38%) 
Ear and labyrinth disorders     
Head, eyes, ears, nose and throat  1  1/268 (0.37%)  1 1/264 (0.38%)  1
Endocrine disorders     
Endocrine  1  1/268 (0.37%)  1 0/264 (0.00%)  0
Gastrointestinal disorders     
Gastrointestinal  1  2/268 (0.75%)  3 5/264 (1.89%)  5
General disorders     
Other  1  2/268 (0.75%)  2 2/264 (0.76%)  2
Infections and infestations     
Infections, non-pneumonia  1  0/268 (0.00%)  0 2/264 (0.76%)  3
Injury, poisoning and procedural complications     
Trauma/Falls  1  2/268 (0.75%)  2 2/264 (0.76%)  2
Musculoskeletal and connective tissue disorders     
Musculoskeletal  1  2/268 (0.75%)  2 1/264 (0.38%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung Cancer  1  1/268 (0.37%)  1 2/264 (0.76%)  2
Other Cancer  1  2/268 (0.75%)  2 1/264 (0.38%)  1
Nervous system disorders     
Neurologic, non-stroke  1  1/268 (0.37%)  1 1/264 (0.38%)  1
Psychiatric disorders     
Psychiatric  1  1/268 (0.37%)  1 0/264 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
COPD Exacerbation  1  55/268 (20.52%)  72 32/264 (12.12%)  47
Pneumonia  1  14/268 (5.22%)  18 11/264 (4.17%)  12
Other Respiratory  1  4/268 (1.49%)  4 1/264 (0.38%)  1
1
Term from vocabulary, ICD-10
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Metoprolol Succinate Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   162/268 (60.45%)      157/264 (59.47%)    
Gastrointestinal disorders     
Gastrointestinal symptoms  1  24/268 (8.96%)  29 30/264 (11.36%)  36
General disorders     
Headache  1  18/268 (6.72%)  21 15/264 (5.68%)  16
Dizziness  1  23/268 (8.58%)  27 16/264 (6.06%)  17
Infections and infestations     
Respiratory Infections  1  30/268 (11.19%)  34 23/264 (8.71%)  30
Respiratory, thoracic and mediastinal disorders     
COPD Exacerbation  1  115/268 (42.91%)  205 122/264 (46.21%)  209
Shortness of Breath  1  20/268 (7.46%)  25 19/264 (7.20%)  24
Acute Sinusitis  1  17/268 (6.34%)  21 10/264 (3.79%)  12
1
Term from vocabulary, ICD-10
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John Connett
Organization: University of Minnesota
Phone: 612-626-9010
EMail: john-c@umn.edu
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT02587351    
Other Study ID Numbers: 1512M81981
First Submitted: October 19, 2015
First Posted: October 27, 2015
Results First Submitted: September 1, 2020
Results First Posted: January 25, 2021
Last Update Posted: January 25, 2021