Trial Outcomes & Findings for Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (NCT NCT02587351)

NCT ID: NCT02587351

Last Updated: 2021-01-25

Results Overview

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".

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

532 participants

Primary outcome timeframe

1 year

Results posted on

2021-01-25

Participant Flow

Participant milestones

Participant milestones
Measure
Metoprolol Succinate
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
Placebo
Matched placebo Placebo: Matching placebo
Overall Study
STARTED
268
264
Overall Study
COMPLETED
268
264
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Total
n=532 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
122 Participants
n=5 Participants
125 Participants
n=7 Participants
247 Participants
n=5 Participants
Age, Categorical
>=65 years
146 Participants
n=5 Participants
139 Participants
n=7 Participants
285 Participants
n=5 Participants
Age, Continuous
65.2 years
STANDARD_DEVIATION 7.6 • n=5 Participants
64.8 years
STANDARD_DEVIATION 7.9 • n=7 Participants
65.0 years
STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male
Female
124 Participants
n=5 Participants
123 Participants
n=7 Participants
247 Participants
n=5 Participants
Sex: Female, Male
Male
144 Participants
n=5 Participants
141 Participants
n=7 Participants
285 Participants
n=5 Participants
Race/Ethnicity, Customized
White
178 Participants
n=5 Participants
194 Participants
n=7 Participants
372 Participants
n=5 Participants
Race/Ethnicity, Customized
Black
83 Participants
n=5 Participants
60 Participants
n=7 Participants
143 Participants
n=5 Participants
Race/Ethnicity, Customized
Other
7 Participants
n=5 Participants
10 Participants
n=7 Participants
17 Participants
n=5 Participants
Region of Enrollment
United States
268 Participants
n=5 Participants
264 Participants
n=7 Participants
532 Participants
n=5 Participants
FEV1 after bronchodilation - % of predicted value
41.3 % of predicted value
STANDARD_DEVIATION 16.3 • n=5 Participants
40.8 % of predicted value
STANDARD_DEVIATION 16.2 • n=7 Participants
41.1 % of predicted value
STANDARD_DEVIATION 16.3 • n=5 Participants
FEV1:FVC ratio - %
44.2 ratio %
STANDARD_DEVIATION 11.7 • n=5 Participants
45.2 ratio %
STANDARD_DEVIATION 21.6 • n=7 Participants
44.7 ratio %
STANDARD_DEVIATION 17.3 • n=5 Participants
Smoking history No. of pack-yr
50.7 pack-years
STANDARD_DEVIATION 28.7 • n=5 Participants
49.5 pack-years
STANDARD_DEVIATION 29.6 • n=7 Participants
50.1 pack-years
STANDARD_DEVIATION 29.1 • n=5 Participants
Systolic Blood pressure - mm Hg
128.4 mm Hg
STANDARD_DEVIATION 16.5 • n=5 Participants
130.6 mm Hg
STANDARD_DEVIATION 15.9 • n=7 Participants
129.5 mm Hg
STANDARD_DEVIATION 16.2 • n=5 Participants
Diastolic Blood pressure - mm Hg
77.2 mm Hg
STANDARD_DEVIATION 9.2 • n=5 Participants
76.8 mm Hg
STANDARD_DEVIATION 9.1 • n=7 Participants
77.0 mm Hg
STANDARD_DEVIATION 9.1 • n=5 Participants

PRIMARY outcome

Timeframe: 1 year

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".

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Time to First Occurrence of an Acute COPS Exacerbation
202 days
Interval 162.0 to 282.0
222 days
Interval 189.0 to 295.0

SECONDARY outcome

Timeframe: 1 year

Number of acute exacerbations of COPD - rate per person-year

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Number of Acute Exacerbations of COPD
1.40 no. of events/person-yr
Interval 1.21 to 1.61
1.33 no. of events/person-yr
Interval 1.15 to 1.54

SECONDARY outcome

Timeframe: 1 year

Number of Emergency Department visits resulting from acute exacerbations of COPD - rate

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Number of Emergency Department Visits Resulting From Acute Exacerbations of COPD
0.17 events per person-year
Interval 0.11 to 0.25
0.18 events per person-year
Interval 0.12 to 0.26

SECONDARY outcome

Timeframe: 1 year

Number of hospital admissions resulting from acute exacerbations of COPD - rate

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Number of Hospital Admissions Resulting From Acute Exacerbations of COPD
0.66 events per person-year
Interval 0.47 to 0.86
0.42 events per person-year
Interval 0.3 to 0.55

SECONDARY outcome

Timeframe: 14 months

Number of hospital days resulting from acute exacerbations of COPD reported as negative binomial estimates of mean hospital days per patient year.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Hospital Days Resulting From Acute Exacerbations of COPD
3.09 hospital days
Interval 2.05 to 4.64
0.96 hospital days
Interval 0.62 to 1.48

SECONDARY outcome

Timeframe: 12 months

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

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Major Adverse Cardiovascular Events
Myocardial Infarction
2 Participants
1 Participants
Major Adverse Cardiovascular Events
Heart Failure
2 Participants
3 Participants
Major Adverse Cardiovascular Events
Stroke
1 Participants
1 Participants
Major Adverse Cardiovascular Events
Sudden Cardiac Death
0 Participants
1 Participants

SECONDARY outcome

Timeframe: 1 year

All-cause mortality count

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
All-cause Mortality
11 Participants
5 Participants

SECONDARY outcome

Timeframe: 1 year

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).

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Incidence of Presumed Metoprolol-related Side-effects
Depression
28 Participants
39 Participants
Incidence of Presumed Metoprolol-related Side-effects
Headache
71 Participants
78 Participants
Incidence of Presumed Metoprolol-related Side-effects
Fainting
4 Participants
8 Participants
Incidence of Presumed Metoprolol-related Side-effects
Daytime Sleepiness
58 Participants
70 Participants
Incidence of Presumed Metoprolol-related Side-effects
Memory Loss
20 Participants
21 Participants
Incidence of Presumed Metoprolol-related Side-effects
Loss of sexual desire or erectile dysfunction
10 Participants
6 Participants
Incidence of Presumed Metoprolol-related Side-effects
Lack of energy
91 Participants
77 Participants
Incidence of Presumed Metoprolol-related Side-effects
Rash
17 Participants
21 Participants
Incidence of Presumed Metoprolol-related Side-effects
Itching
11 Participants
18 Participants
Incidence of Presumed Metoprolol-related Side-effects
Tongue or facial swelling
7 Participants
5 Participants
Incidence of Presumed Metoprolol-related Side-effects
Vomiting
11 Participants
18 Participants
Incidence of Presumed Metoprolol-related Side-effects
Nausea
45 Participants
42 Participants
Incidence of Presumed Metoprolol-related Side-effects
Constipation
30 Participants
32 Participants
Incidence of Presumed Metoprolol-related Side-effects
Wheezing
88 Participants
79 Participants
Incidence of Presumed Metoprolol-related Side-effects
Shortness of breath
115 Participants
112 Participants
Incidence of Presumed Metoprolol-related Side-effects
Chest tightness
81 Participants
80 Participants
Incidence of Presumed Metoprolol-related Side-effects
Heart skipping or irregular beats
16 Participants
15 Participants
Incidence of Presumed Metoprolol-related Side-effects
Dizziness/light headedness
74 Participants
64 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Participants with data at baseline and visit day 336

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=207 Participants
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
Placebo
n=201 Participants
Matched placebo Placebo: Matching placebo
Modified Medical Research Council Dyspnea Scale (MMRC)
2.0 score on a scale
Interval 1.0 to 3.0
2.0 score on a scale
Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants with data at baseline and visit day 336

Change in FEV1 % Predicted from baseline to visit day 336 as assessed by spirometry

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=193 Participants
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
Placebo
n=197 Participants
Matched placebo Placebo: Matching placebo
Forced Expiratory Volume in 1 Second (FEV1)
-2.24 percentage of predicted
Interval -3.28 to -1.2
-1.46 percentage of predicted
Interval -2.5 to -0.42

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: Participants with data at baseline and visit day 336

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=174 Participants
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
Placebo
n=166 Participants
Matched placebo Placebo: Matching placebo
Exercise Capacity as Assessed by the 6 Minute Walk Distance (6MWD)
-17.64 meters
Interval -28.75 to -6.53
-11.87 meters
Interval -23.21 to -0.54

SECONDARY outcome

Timeframe: Baseline, 1 year

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Markers of Systemic Inflammation
Fibrinogen baseline
384.8 mg/dL
Standard Deviation 94.6
378.2 mg/dL
Standard Deviation 91.9
Markers of Systemic Inflammation
Fibrinogen Visit 336
392.5 mg/dL
Standard Deviation 90.5
386.0 mg/dL
Standard Deviation 110.0

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: Participants with data at baseline and visit day 336

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=203 Participants
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
Placebo
n=200 Participants
Matched placebo Placebo: Matching placebo
St. George's Respiratory Questionnaire (SGRQ)
0.52 score on a scale
Interval -1.01 to 2.04
-0.25 score on a scale
Interval -1.79 to 1.28

SECONDARY outcome

Timeframe: Baseline, 1 year

Population: Participants with data at baseline and visit day 336

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=206 Participants
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
Placebo
n=200 Participants
Matched placebo Placebo: Matching placebo
COPD Assessment Test (CAT)
0.88 score on a scale
Interval 0.07 to 1.69
-0.59 score on a scale
Interval -1.41 to 0.23

SECONDARY outcome

Timeframe: 1 year

Population: Participants with data at baseline and visit day 336

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").

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=204 Participants
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
Placebo
n=199 Participants
Matched placebo Placebo: Matching placebo
San Diego Shortness of Breath Questionnaire (SOBQ)
0.52 score on a scale
Interval -1.01 to 2.04
-0.25 score on a scale
Interval -1.79 to 1.28

SECONDARY outcome

Timeframe: 12 months

MACE defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=268 Participants
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
Placebo
n=264 Participants
Matched placebo Placebo: Matching placebo
Acute Exacerbations of COPD and MACE
Myocardial Infarction
2 Participants
1 Participants
Acute Exacerbations of COPD and MACE
Heart Failure
2 Participants
3 Participants
Acute Exacerbations of COPD and MACE
Stroke
1 Participants
1 Participants
Acute Exacerbations of COPD and MACE
Sudden cardiac death
0 Participants
1 Participants
Acute Exacerbations of COPD and MACE
COPD Exacerbation (Serious)
55 Participants
32 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Physical Function Scale
Baseline
30.0 Units on a scale
Interval 15.0 to 50.0
30.0 Units on a scale
Interval 15.0 to 45.0
Short Form Health Survey (SF-36) Physical Function Scale
Day 112 visit
30.0 Units on a scale
Interval 15.0 to 55.0
30.0 Units on a scale
Interval 15.0 to 50.0
Short Form Health Survey (SF-36) Physical Function Scale
Day 336 Visit
30.0 Units on a scale
Interval 15.0 to 50.0
35.0 Units on a scale
Interval 15.0 to 50.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Role Functioning - Physical Scale
Baseline
25.0 Units on a scale
Interval 0.0 to 50.0
25.0 Units on a scale
Interval 0.0 to 56.2
Short Form Health Survey (SF-36) Role Functioning - Physical Scale
Day 112 visit
25.0 Units on a scale
Interval 0.0 to 75.0
25.0 Units on a scale
Interval 0.0 to 75.0
Short Form Health Survey (SF-36) Role Functioning - Physical Scale
Day 336 Visit
12.5 Units on a scale
Interval 0.0 to 75.0
12.5 Units on a scale
Interval 0.0 to 50.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
Baseline
100.0 Units on a scale
Interval 0.0 to 100.0
66.7 Units on a scale
Interval 0.0 to 100.0
Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
Day 112 visit
66.7 Units on a scale
Interval 0.0 to 100.0
66.7 Units on a scale
Interval 0.0 to 100.0
Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
Day 336 Visit
66.7 Units on a scale
Interval 0.0 to 100.0
66.7 Units on a scale
Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Energy/Fatigue Scale
Baseline
50.0 Units on a scale
Interval 35.0 to 60.0
50.0 Units on a scale
Interval 35.0 to 60.0
Short Form Health Survey (SF-36) Energy/Fatigue Scale
Day 112 visit
50.0 Units on a scale
Interval 35.0 to 60.0
45.0 Units on a scale
Interval 30.0 to 60.0
Short Form Health Survey (SF-36) Energy/Fatigue Scale
Day 336 Visit
50.0 Units on a scale
Interval 35.0 to 60.0
45.0 Units on a scale
Interval 30.0 to 55.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Emotional Well-being Scale
Baseline
76.0 Units on a scale
Interval 60.0 to 84.0
72.0 Units on a scale
Interval 56.0 to 84.0
Short Form Health Survey (SF-36) Emotional Well-being Scale
Day 112 visit
76.0 Units on a scale
Interval 60.0 to 88.0
72.0 Units on a scale
Interval 56.0 to 84.0
Short Form Health Survey (SF-36) Emotional Well-being Scale
Day 336 Visit
76.0 Units on a scale
Interval 60.0 to 88.0
72.0 Units on a scale
Interval 56.0 to 84.0

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Social Functioning Scale
Baseline
62.5 Units on a scale
Interval 50.0 to 87.5
62.5 Units on a scale
Interval 50.0 to 87.5
Short Form Health Survey (SF-36) Social Functioning Scale
Day 112 visit
62.5 Units on a scale
Interval 50.0 to 87.5
62.5 Units on a scale
Interval 50.0 to 87.5
Short Form Health Survey (SF-36) Social Functioning Scale
Day 336 Visit
75.0 Units on a scale
Interval 50.0 to 87.5
62.5 Units on a scale
Interval 37.5 to 87.5

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) Bodily Pain Scale
Baseline
67.5 Units on a scale
Interval 45.0 to 90.0
67.5 Units on a scale
Interval 45.0 to 90.0
Short Form Health Survey (SF-36) Bodily Pain Scale
Day 112 visit
67.5 Units on a scale
Interval 45.0 to 90.0
67.5 Units on a scale
Interval 45.0 to 90.0
Short Form Health Survey (SF-36) Bodily Pain Scale
Day 336 Visit
57.5 Units on a scale
Interval 35.0 to 90.0
57.5 Units on a scale
Interval 42.5 to 87.5

SECONDARY outcome

Timeframe: 1 year

Population: Participants with SF-36 data available

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.

Outcome measures

Outcome measures
Measure
Metoprolol Succinate
n=265 Participants
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
Placebo
n=262 Participants
Matched placebo Placebo: Matching placebo
Short Form Health Survey (SF-36) General Health Scale
Baseline
40.0 Units on a scale
Interval 25.0 to 55.0
40.0 Units on a scale
Interval 25.0 to 55.0
Short Form Health Survey (SF-36) General Health Scale
Day 112 visit
40.0 Units on a scale
Interval 25.0 to 55.0
35.0 Units on a scale
Interval 25.0 to 55.0
Short Form Health Survey (SF-36) General Health Scale
Day 336 Visit
40.0 Units on a scale
Interval 25.0 to 55.0
35.0 Units on a scale
Interval 25.0 to 50.0

Adverse Events

Metoprolol Succinate

Serious events: 86 serious events
Other events: 162 other events
Deaths: 11 deaths

Placebo

Serious events: 59 serious events
Other events: 157 other events
Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure
Metoprolol Succinate
n=268 participants at risk
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
Placebo
n=264 participants at risk
Matched placebo Placebo: Matching placebo
Cardiac disorders
Myocardial infarction
0.75%
2/268 • Number of events 2 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Cardiac disorders
Heart failure
0.75%
2/268 • Number of events 2 • 1 year
1.1%
3/264 • Number of events 3 • 1 year
Cardiac disorders
Stroke
0.37%
1/268 • Number of events 1 • 1 year
0.38%
1/264 • Number of events 2 • 1 year
Cardiac disorders
Arrhythmias
0.75%
2/268 • Number of events 2 • 1 year
0.76%
2/264 • Number of events 2 • 1 year
Cardiac disorders
Hypotension
0.00%
0/268 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Cardiac disorders
Other Cardiovascular
0.37%
1/268 • Number of events 1 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation
20.5%
55/268 • Number of events 72 • 1 year
12.1%
32/264 • Number of events 47 • 1 year
Respiratory, thoracic and mediastinal disorders
Pneumonia
5.2%
14/268 • Number of events 18 • 1 year
4.2%
11/264 • Number of events 12 • 1 year
Respiratory, thoracic and mediastinal disorders
Other Respiratory
1.5%
4/268 • Number of events 4 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Gastrointestinal disorders
Gastrointestinal
0.75%
2/268 • Number of events 3 • 1 year
1.9%
5/264 • Number of events 5 • 1 year
Musculoskeletal and connective tissue disorders
Musculoskeletal
0.75%
2/268 • Number of events 2 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Cancer
0.37%
1/268 • Number of events 1 • 1 year
0.76%
2/264 • Number of events 2 • 1 year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other Cancer
0.75%
2/268 • Number of events 2 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Infections and infestations
Infections, non-pneumonia
0.00%
0/268 • 1 year
0.76%
2/264 • Number of events 3 • 1 year
Ear and labyrinth disorders
Head, eyes, ears, nose and throat
0.37%
1/268 • Number of events 1 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Injury, poisoning and procedural complications
Trauma/Falls
0.75%
2/268 • Number of events 2 • 1 year
0.76%
2/264 • Number of events 2 • 1 year
Nervous system disorders
Neurologic, non-stroke
0.37%
1/268 • Number of events 1 • 1 year
0.38%
1/264 • Number of events 1 • 1 year
Psychiatric disorders
Psychiatric
0.37%
1/268 • Number of events 1 • 1 year
0.00%
0/264 • 1 year
Cardiac disorders
Chest Pain, not otherwise specified
0.37%
1/268 • Number of events 1 • 1 year
0.38%
1/264 • 1 year
Endocrine disorders
Endocrine
0.37%
1/268 • Number of events 1 • 1 year
0.00%
0/264 • 1 year
General disorders
Other
0.75%
2/268 • Number of events 2 • 1 year
0.76%
2/264 • Number of events 2 • 1 year

Other adverse events

Other adverse events
Measure
Metoprolol Succinate
n=268 participants at risk
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
Placebo
n=264 participants at risk
Matched placebo Placebo: Matching placebo
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation
42.9%
115/268 • Number of events 205 • 1 year
46.2%
122/264 • Number of events 209 • 1 year
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
7.5%
20/268 • Number of events 25 • 1 year
7.2%
19/264 • Number of events 24 • 1 year
Respiratory, thoracic and mediastinal disorders
Acute Sinusitis
6.3%
17/268 • Number of events 21 • 1 year
3.8%
10/264 • Number of events 12 • 1 year
General disorders
Headache
6.7%
18/268 • Number of events 21 • 1 year
5.7%
15/264 • Number of events 16 • 1 year
Gastrointestinal disorders
Gastrointestinal symptoms
9.0%
24/268 • Number of events 29 • 1 year
11.4%
30/264 • Number of events 36 • 1 year
General disorders
Dizziness
8.6%
23/268 • Number of events 27 • 1 year
6.1%
16/264 • Number of events 17 • 1 year
Infections and infestations
Respiratory Infections
11.2%
30/268 • Number of events 34 • 1 year
8.7%
23/264 • Number of events 30 • 1 year

Additional Information

John Connett

University of Minnesota

Phone: 612-626-9010

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place