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
Last Update Posted : November 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Disease, Chronic Obstructive||Drug: Metoprolol succinate Other: Placebo||Phase 3|
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.
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.
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||532 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Beta-Blockers for the Prevention of Acute Exacerbations of COPD|
|Actual Study Start Date :||May 1, 2016|
|Actual Primary Completion Date :||September 1, 2019|
|Actual Study Completion Date :||September 1, 2019|
Active Comparator: 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).
Drug: Metoprolol succinate
Extended release Metoprolol succinate
Placebo Comparator: Placebo
- First occurrence of an acute COPD 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".
- Number of acute exacerbations of COPD [ Time Frame: 1 year ]Number of acute exacerbations of COPD
- Number of Emergency Department visits resulting from acute exacerbations of COPD [ Time Frame: 1 year ]Number of Emergency Department visits resulting from acute exacerbations of COPD
- Number of hospital admissions resulting from acute exacerbations of COPD [ Time Frame: 1 year ]Number of hospital admissions resulting from acute exacerbations of COPD
- Number of hospital days resulting from acute exacerbations of COPD [ Time Frame: 1 year ]Number of hospital days resulting from acute exacerbations of COPD
- Rate of major adverse cardiovascular events (MACE), percutaneous coronary intervention or coronary artery bypass grafting [ Time Frame: 1 year ]MACE defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke
- All-cause mortality [ Time Frame: 1 year ]All-cause mortality
- Incidence of presumed metoprolol-related side-effects [ Time Frame: 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).
- Short Form Health Survey (SF-36) [ Time Frame: 1 year ]SF-36 is a generic tool to assess overall health status and allows comparison between different diseases.
- Modified Medical Research Council Dyspnea Scale (MMRC) [ Time Frame: 1 year ]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.
- Forced expiratory volume in 1 second (FEV1) [ Time Frame: 1 year ]FEV1 as assessed by spirometry
- Exercise capacity as assessed by the 6 minute walk distance (6MWD) [ Time Frame: 1 year ]The 6MWD has been used as a simple tool to assess overall exercise tolerance in patients with chronic cardiopulmonary disease including COPD.
- Markers of cardiac stretch, injury and systemic inflammation [ Time Frame: 1 year ]troponin-I, pro-NT Brain Natriuretic Peptide, high sensitivity C-reactive protein, and fibrinogen: These parameters will be assessed at screening/randomization and at conclusion of the study to determine if beta-blockade impacts volume status and cardiac performance as well as levels of systemic inflammation that portend overall cardiac risk.
- St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: 1 year ]The SGRQ is a respiratory specific health status questionnaire with scores ranging from 0 to 100. The lower score indicates a better health status.
- COPD Assessment Test (CAT) [ Time Frame: 1 year ]The CAT is a simple, eight item, health status instrument for patients with COPD. Lower scores denote better health status.
- San Diego Shortness of Breath Questionnaire (SOBQ) [ Time Frame: 1 year ]A 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living.
- Combined rate of acute exacerbations of COPD and MACE [ Time Frame: 1 year ]MACE defined by cardiovascular death, hospitalization for myocardial infarction, heart failure, or stroke
- Serum Biomarkers [ Time Frame: 1 year ]Serum Biomarkers
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02587351
|Principal Investigator:||Mark Dransfield, MD||University of Alabama at Birmingham|
|Principal Investigator:||John Connett, PhD||University of Minnesota|
|Principal Investigator:||Stephen Lazarus, MD||University of California, San Francisco|