Pulmonary Disease, Chronic ObstructivePhase 3NCT02587351
Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease
A Phase 3 study testing Metoprolol succinate in people with Pulmonary Disease, Chronic Obstructive, run by University of Minnesota at 27 sites in United States.
Trial summary
This is a multicenter, prospective, randomized, double-blind, placebo-controlled trial that will enroll 1028 patients with at least moderately severe COPD over a three year period and follow them at regular intervals for one year. The primary endpoint is time to first acute exacerbation. Read more about this study
- Who is it for?
- Ages 40 to 84 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Metoprolol succinate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 532 participants
- Where
- 27 sitesUnited States
- Study dates
- 1 May 2016to 1 Dec 2019
- 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 40 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects, ≥ 40 and less than 85 years of age
- Clinical diagnosis of at least moderate COPD as defined by the Global Initiative for Obstructive Lung Disease (GOLD) criteria (53):
- Post bronchodilator FEV1/FVC < 70% (Forced expiratory volume in 1 second/ forced vital capacity),
- Post bronchodilator FEV1 < 80% predicted, with or without chronic symptoms (i.e., cough, sputum production).
- Cigarette consumption of 10 pack-years or more. Patients may or may not be active smokers.
- To enrich the population for patients who are more likely to have acute exacerbations (54), each subject must meet one or more of the following 4 conditions:
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- Have a history of receiving a course of systemic corticosteroids and/or antibiotics for respiratory problems in the past year,
- Visiting an Emergency Department for a COPD exacerbation within the past year, or
- Being hospitalized for a COPD exacerbation within the past year
- Be using or be prescribed supplemental oxygen for 12 or more hours per day
- Willingness to make return visits and availability by telephone for duration of study.
Who cannot join
- A diagnosis of asthma established by each study investigator on the basis of the recent American Thoracic Society/European Respiratory Society and National Institute for Health and Care Excellence guidelines.
- The presence of a diagnosis other than COPD that results in the patient being either medically unstable, or having a predicted life expectancy < 2 years.
- Women who are at risk of becoming pregnant during the study (pre-menopausal) and who refuse to use acceptable birth control (hormone-based oral or barrier contraceptive) for the duration of the study.
- Current tachy or brady arrhythmias requiring treatment
- Presence of a pacemaker and/or internal cardioverter/defibrillator
- Patients with a history of second or third degree (complete) heart block, or sick sinus syndrome
Show all 17Show fewer
- Baseline EKG revealing left bundle branch block, bifascicular block, ventricular tachyarrhythmia, atrial fibrillation, atrial flutter, supraventricular tachycardia (other than sinus tachycardia and multifocal atrial tachycardia), or heart block (2nd degree or complete)
- Resting heart rate less than 65 beats per minute, or sustained resting tachycardia defined as heart rate greater than 120 beats per minute.
- Resting systolic blood pressure of less than 100mm Hg.
- Subjects with absolute (Class 1) indications for beta-blocker treatment as defined by the combined American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Guidelines which include myocardial infarction, acute coronary syndrome, percutaneous coronary intervention or coronary artery bypass surgery within the prior 3 years and patients with known congestive heart failure defined as left ventricular ejection fraction <40%.(29, 30)
- Critical ischemia related to peripheral arterial disease.
- Other diseases that are known to be triggered by beta-blockers or beta-blocker withdrawal including myasthenia gravis, periodic hypokalemic paralysis, pheochromocytoma, and thyrotoxicosis
- Patients on other cardiac medications known to cause atrioventricular (AV) node conduction delays such as amiodarone, digoxin, and calcium channel blockers including verapamil and diltiazem as well as patients taking clonidine.
- Hospitalization for uncontrolled diabetes mellitus or hypoglycemia within the last 12 months.
- Patients with cirrhosis
- A clinical diagnosis of bronchiectasis defined as production of > one-half cup of purulent sputum/day.
- Patients otherwise meeting the inclusion criteria will not be enrolled until they are a minimum of four weeks from their most recent acute exacerbation (i.e., they will not have received a course of systemic corticosteroids, an increased dose of chronically administered systemic corticosteroids, and/or antibiotics for an acute exacerbation for a minimum of four weeks).
Trial locations and contacts
27 sites in 1 country.
27 sites in 1 country
United States27 sites
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, 48105
University of Michigan
Ann Arbor, Michigan, 48109
University of Maryland Baltimore
Baltimore, Maryland, 21201
Birmingham, Alabama VA Medical
Birmingham, Alabama, 35233
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Brigham and Women's Hospital
Boston, Massachusetts, 02115
NewYork-Presbyterian Brooklyn Methodist Hospital
Brooklyn, New York, 11215
The University of Vermont
Burlington, Vermont, 05405
Northwestern University
Chicago, Illinois, 60611
Cincinnati VA Medical Center
Cincinnati, Ohio, 45220
Cleveland Clinic
Cleveland, Ohio, 44195
National Jewish Medical & Research Center
Denver, Colorado, 80206
New York Presbyterian/Queens
Flushing, New York, 11355
University of California, San Francisco-Fresno
Fresno, California, 93701
North Florida/South Georgia Veterans Health System
Gainesville, Florida, 32608
Cornell University
Ithaca, New York, 14853
LA BioMed at Harbor-UCLA Medical Center
Los Angeles, California, 90502
Veteran's Administration Medical Center
Minneapolis, Minnesota, 55417
HealthPartners Research Foundation
Minneapolis, Minnesota, 55440
Louisiana State University
New Orleans, Louisiana, 70112
Columbia University
New York, New York, 10027
Temple University Lung Center
Philadelphia, Pennsylvania, 19140
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132-4701
University of California at San Francisco
San Francisco, California, 94143
University of Washington School of Medicine
Spokane, Washington, 99258
About this study
Official title: Beta-Blockers for the Prevention of Acute Exacerbations of COPD
This is a multicenter, prospective, randomized, double-blind, placebo-controlled trial that will enroll 1028 patients with at least moderately severe COPD over a three year period and follow them at regular intervals for one year. The primary endpoint is time to first acute exacerbation. Secondary endpoints include rates and severity of COPD exacerbations, cardiovascular events, all-cause mortality, lung function, dyspnea, quality of life and metoprolol-related side effects.
Read the detailed description
Hypothesis The primary hypothesis is that metoprolol succinate will reduce the risk of COPD exacerbations as compared to placebo. The secondary hypothesis is that metoprolol succinate will not adversely impact lung function, exercise tolerance, dyspnea or quality of life as compared to placebo.
Study Flow Patients will be screened and then randomized over a 2 week period and will then undergo a dose titration period for the following six weeks. Thereafter patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4 week washout period.
Specific Aims:
Primary: To determine the effect of once daily metoprolol succinate compared with placebo on the time to first exacerbation in moderate to severe COPD patients who are prone to exacerbations and who do not have absolute indications for beta-blocker therapy.
Secondary: To estimate the effect of metoprolol succinate compared with placebo on:
- The rate and severity of COPD exacerbations over 12 months
- Incidence and severity of metoprolol-related side effects including those that require cessation of drug
- Lung function as assessed by spirometry, dyspnea as assessed by the Modified Medical Research Council Scale (MMRC) and San Diego Shortness of Breath Questionnaire, exercise tolerance as measured by six minute walk test (6MWD), and quality of life as assessed by the Short Form 36, St. Georges Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) and Personal HEART Score.
- Hospitalizations
- The rate of major adverse cardiovascular events (MACE) (defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke), percutaneous coronary intervention or coronary artery bypass grafting
- All-cause mortality
Secondary subgroup analyses for 1) cardiovascular risk based on Personal HEART Score and 2) age greater versus less than 65.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Metoprolol succinate, Placebo
- Keywords
- Chronic Obstructive Pulmonary Disease, COPD, Exacerbation, Lung function, Cardiac, Cardiovascular, Beta blockers, Metoprolol succinate, Smoking
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metoprolol succinateDrug
Also called Metoprolol Succinate ER, Toprol XL
Extended release Metoprolol succinate
PlaceboOther
Matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Metoprolol succinate | Active comparator | 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). Receives: Drug: Metoprolol succinate |
| Placebo | Placebo comparator | Matched placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First Occurrence of an Acute COPS Exacerbation
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".
Measured: 1 year
Secondary outcomes (23)
Number of Acute Exacerbations of COPD
Number of acute exacerbations of COPD - rate per person-year
Measured: 1 year
Number of Emergency Department Visits Resulting From Acute Exacerbations of COPD
Number of Emergency Department visits resulting from acute exacerbations of COPD - rate
Measured: 1 year
Number of Hospital Admissions Resulting From Acute Exacerbations of COPD
Number of hospital admissions resulting from acute exacerbations of COPD - rate
Measured: 1 year
Hospital Days Resulting From Acute Exacerbations of COPD
Number of hospital days resulting from acute exacerbations of COPD reported as negative binomial estimates of mean hospital days per patient year.
Measured: 14 months
Major Adverse Cardiovascular Events
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
Measured: 12 months
All-cause Mortality
All-cause mortality count
Measured: 1 year
Incidence of Presumed Metoprolol-related Side-effects
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).
Measured: 1 year
Modified Medical Research Council Dyspnea Scale (MMRC)
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.
Measured: 1 year
Forced Expiratory Volume in 1 Second (FEV1)
Change in FEV1 % Predicted from baseline to visit day 336 as assessed by spirometry
Measured: 1 year
Exercise Capacity as Assessed by the 6 Minute Walk Distance (6MWD)
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.
Measured: Baseline, 1 year
Markers of Systemic Inflammation
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.
Measured: Baseline, 1 year
St. George's Respiratory Questionnaire (SGRQ)
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.
Measured: Baseline, 1 year
COPD Assessment Test (CAT)
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.
Measured: Baseline, 1 year
San Diego Shortness of Breath Questionnaire (SOBQ)
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").
Measured: 1 year
Acute Exacerbations of COPD and MACE
MACE defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke
Measured: 12 months
Short Form Health Survey (SF-36) Physical Function Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) Role Functioning - Physical Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) Energy/Fatigue Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) Emotional Well-being Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) Social Functioning Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) Bodily Pain Scale
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.
Measured: 1 year
Short Form Health Survey (SF-36) General Health Scale
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study start1 May 2016
- Primary completion1 Sep 2019
- Study completion1 Dec 2019
Why it stopped: Futility
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- 532 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, University of Alabama at Birmingham
- Responsible party
- Sponsor
- Investigators
- Mark Dransfield, MD, Principal investigator, University of Alabama at BirminghamJohn Connett, PhD, Principal investigator, University of MinnesotaStephen Lazarus, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02587351
- Sponsor's protocol ID
- 1512M81981
- Status last verified
- Jan 2021
- First submitted
- 19 Oct 2015
- Last updated
- 25 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Parekh TM, Helgeson ES, Connett J, Voelker H, Ling SX, Lazarus SC, Bhatt SP, MacDonald DM, Mkorombindo T, Kunisaki KM, Fortis S, Kaminsky D, Dransfield MT. Lung Function and the Risk of Exacerbation in the beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial. Ann Am Thorac Soc. 2022 Oct;19(10):1642-1649. doi: 10.1513/AnnalsATS.202109-1042OC.
PubMed 35363600Dransfield MT, Voelker H, Bhatt SP, Brenner K, Casaburi R, Come CE, Cooper JAD, Criner GJ, Curtis JL, Han MK, Hatipoglu U, Helgeson ES, Jain VV, Kalhan R, Kaminsky D, Kaner R, Kunisaki KM, Lambert AA, Lammi MR, Lindberg S, Make BJ, Martinez FJ, McEvoy C, Panos RJ, Reed RM, Scanlon PD, Sciurba FC, Smith A, Sriram PS, Stringer WW, Weingarten JA, Wells JM, Westfall E, Lazarus SC, Connett JE; BLOCK COPD Trial Group. Metoprolol for the Prevention of Acute Exacerbations of COPD. N Engl J Med. 2019 Dec 12;381(24):2304-2314. doi: 10.1056/NEJMoa1908142. Epub 2019 Oct 20.
PubMed 31633896Bhatt SP, Connett JE, Voelker H, Lindberg SM, Westfall E, Wells JM, Lazarus SC, Criner GJ, Dransfield MT. beta-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (betaLOCK COPD): a randomised controlled study protocol. BMJ Open. 2016 Jun 7;6(6):e012292. doi: 10.1136/bmjopen-2016-012292.
PubMed 27267111
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta-Blockers for the Prevention of Acute Exacerbations of COPD
- ClinicalTrials.gov ID
- NCT02587351
- Acronym / sponsor ID
- 1512M81981
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- Chronic Obstructive Pulmonary Disease, COPD, Exacerbation, Lung function, Cardiac, Cardiovascular, Beta blockers, Metoprolol succinate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 532 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- United States Department of Defense, University of Alabama at Birmingham
- Study start
- 1 May 2016 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Posted 25 Jan 2021
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 multicenter, prospective, randomized, double-blind, placebo-controlled trial that will enroll 1028 patients with at least moderately severe COPD over a three year period and follow them at regular intervals for one year. The primary endpoint is time to first acute exacerbation. Secondary endpoints include rates and severity of COPD exacerbations, cardiovascular events, all-cause mortality, lung function, dyspnea, quality of life and metoprolol-related side effects.
Detailed description
Hypothesis The primary hypothesis is that metoprolol succinate will reduce the risk of COPD exacerbations as compared to placebo. The secondary hypothesis is that metoprolol succinate will not adversely impact lung function, exercise tolerance, dyspnea or quality of life as compared to placebo.
Study Flow Patients will be screened and then randomized over a 2 week period and will then undergo a dose titration period for the following six weeks. Thereafter patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4 week washout period.
Specific Aims:
Primary: To determine the effect of once daily metoprolol succinate compared with placebo on the time to first exacerbation in moderate to severe COPD patients who are prone to exacerbations and who do not have absolute indications for beta-blocker therapy.
Secondary: To estimate the effect of metoprolol succinate compared with placebo on:
- The rate and severity of COPD exacerbations over 12 months
- Incidence and severity of metoprolol-related side effects including those that require cessation of drug
- Lung function as assessed by spirometry, dyspnea as assessed by the Modified Medical Research Council Scale (MMRC) and San Diego Shortness of Breath Questionnaire, exercise tolerance as measured by six minute walk test (6MWD), and quality of life as assessed by the Short Form 36, St. Georges Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) and Personal HEART Score.
- Hospitalizations
- The rate of major adverse cardiovascular events (MACE) (defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke), percutaneous coronary intervention or coronary artery bypass grafting
- All-cause mortality
Secondary subgroup analyses for 1) cardiovascular risk based on Personal HEART Score and 2) age greater versus less than 65.
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 |
|---|---|---|
| Metoprolol succinate | Active comparator | Drug: Metoprolol succinateMetoprolol 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). |
| Placebo | Placebo comparator | Other: PlaceboMatched placebo |
Who may qualify
- Ages
- 40 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male and female subjects, ≥ 40 and less than 85 years of age
- Clinical diagnosis of at least moderate COPD as defined by the Global Initiative for Obstructive Lung Disease (GOLD) criteria (53):
- Cigarette consumption of 10 pack-years or more. Patients may or may not be active smokers.
- To enrich the population for patients who are more likely to have acute exacerbations (54), each subject must meet one or more of the following 4 conditions:
Key exclusion criteria (17 listed)
- A diagnosis of asthma established by each study investigator on the basis of the recent American Thoracic Society/European Respiratory Society and National Institute for Health and Care Excellence guidelines.
- The presence of a diagnosis other than COPD that results in the patient being either medically unstable, or having a predicted life expectancy < 2 years.
- Women who are at risk of becoming pregnant during the study (pre-menopausal) and who refuse to use acceptable birth control (hormone-based oral or barrier contraceptive) for the duration of the study.
- Current tachy or brady arrhythmias requiring treatment
- Presence of a pacemaker and/or internal cardioverter/defibrillator
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 |
|---|---|---|
| Metoprolol succinateAlso: Metoprolol Succinate ER, Toprol XLExtended release Metoprolol succinate | Drug | Metoprolol succinate |
| PlaceboMatching placebo | Other | Placebo |
Primary outcome
Time to First Occurrence of an Acute COPS Exacerbation
Time frame: 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".
23 secondary outcomes
Number of Acute Exacerbations of COPD
Time frame: 1 year
Number of Emergency Department Visits Resulting From Acute Exacerbations of COPD
Time frame: 1 year
Number of Hospital Admissions Resulting From Acute Exacerbations of COPD
Time frame: 1 year
Hospital Days Resulting From Acute Exacerbations of COPD
Time frame: 14 months
Major Adverse Cardiovascular Events
Time frame: 12 months
All-cause Mortality
Time frame: 1 year
Incidence of Presumed Metoprolol-related Side-effects
Time frame: 1 year
Modified Medical Research Council Dyspnea Scale (MMRC)
Time frame: 1 year
Forced Expiratory Volume in 1 Second (FEV1)
Time frame: 1 year
Exercise Capacity as Assessed by the 6 Minute Walk Distance (6MWD)
Time frame: Baseline, 1 year
Markers of Systemic Inflammation
Time frame: Baseline, 1 year
St. George's Respiratory Questionnaire (SGRQ)
Time frame: Baseline, 1 year
COPD Assessment Test (CAT)
Time frame: Baseline, 1 year
San Diego Shortness of Breath Questionnaire (SOBQ)
Time frame: 1 year
Acute Exacerbations of COPD and MACE
Time frame: 12 months
Short Form Health Survey (SF-36) Physical Function Scale
Time frame: 1 year
Short Form Health Survey (SF-36) Role Functioning - Physical Scale
Time frame: 1 year
Short Form Health Survey (SF-36) Role Functioning - Emotional Scale
Time frame: 1 year
Short Form Health Survey (SF-36) Energy/Fatigue Scale
Time frame: 1 year
Short Form Health Survey (SF-36) Emotional Well-being Scale
Time frame: 1 year
Short Form Health Survey (SF-36) Social Functioning Scale
Time frame: 1 year
Short Form Health Survey (SF-36) Bodily Pain Scale
Time frame: 1 year
Short Form Health Survey (SF-36) General Health Scale
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35363600Parekh TM, Helgeson ES, Connett J, Voelker H, Ling SX, Lazarus SC, Bhatt SP, MacDonald DM, Mkorombindo T, Kunisaki KM, Fortis S, Kaminsky D, Dransfield MT. Lung Function and the Risk of Exacerbation in the beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial. Ann Am Thorac Soc. 2022 Oct;19(10):1642-1649. doi: 10.1513/AnnalsATS.202109-1042OC.
- Derived from this study: PubMed 31633896Dransfield MT, Voelker H, Bhatt SP, Brenner K, Casaburi R, Come CE, Cooper JAD, Criner GJ, Curtis JL, Han MK, Hatipoglu U, Helgeson ES, Jain VV, Kalhan R, Kaminsky D, Kaner R, Kunisaki KM, Lambert AA, Lammi MR, Lindberg S, Make BJ, Martinez FJ, McEvoy C, Panos RJ, Reed RM, Scanlon PD, Sciurba FC, Smith A, Sriram PS, Stringer WW, Weingarten JA, Wells JM, Westfall E, Lazarus SC, Connett JE; BLOCK COPD Trial Group. Metoprolol for the Prevention of Acute Exacerbations of COPD. N Engl J Med. 2019 Dec 12;381(24):2304-2314. doi: 10.1056/NEJMoa1908142. Epub 2019 Oct 20.
- Derived from this study: PubMed 27267111Bhatt SP, Connett JE, Voelker H, Lindberg SM, Westfall E, Wells JM, Lazarus SC, Criner GJ, Dransfield MT. beta-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (betaLOCK COPD): a randomised controlled study protocol. BMJ Open. 2016 Jun 7;6(6):e012292. doi: 10.1136/bmjopen-2016-012292.
- Individual participant dataSharing planned: No
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Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
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.
Mark Dransfield, MD principal investigator
University of Alabama at Birmingham
John Connett, PhD principal investigator
University of Minnesota
Stephen Lazarus, MD principal investigator
University of California, San Francisco
27 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metoprolol succinate in people with Pulmonary Disease, Chronic Obstructive, run by University of Minnesota at 27 sites 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 11 inclusion and 17 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: stopped early, as of the sponsor's last update on 25 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites 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. Some participants in this study may receive a placebo. 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 25 Jan 2021). 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?
Time to First Occurrence of an Acute COPS Exacerbation (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02587351, which also lists 3 linked publications.
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 25 Jan 2021.