Tolerability of Metoprolol-Succinate-ER and Carvedilol in COPD

Study Overview
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Brief Summary
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Use of beta-blockers has proven beneficial in patients with hypertension, heart failure, and in people who have suffered a heart attack. The use in patients who have Chronic Obstructive Pulmonary Disease (COPD) and reactive airway disease, however, has been limited due to possible side effects such as worsening of lung function or increasing airway spasms and asthma attacks. The purpose of this study is to find out if patients with COPD can tolerate being on a beta-blocker at doses recommended for the treatment of heart disease conditions. This study also seeks to find out if a selective beta-1 receptor beta-blocker is better than a non-selective beta-blocker in patients with mild to moderate COPD.

Official Title
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Randomized Open-Label Crossover Trial Comparing Tolerability of a Cardioselective Beta-Blocker (Metoprolol-Succinate-ER) and a Non-Cardioselective Beta-Blocker (Carvedilol) in Patients With Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Disease, Chronic Obstructive, Asthma, Adverse Effect of Beta-adrenoreceptor Antagonists

Intervention / Treatment
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* Drug: Metoprolol succinate ER
* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 years of age or older Mild to moderate COPD as defined by the American Thoracic Society Current treatment with a beta-blocker for either hypertension, myocardial infarction, or congestive heart failure. Exclusion Criteria: Recent (within 30 days) COPD exacerbation or requirement for oral steroid therapy within the last 6 months Any history of ventilator support requirement for COPD Patients with asthma or reactive airway disease (RAD) defined as obstructive lung disease with a >15% improvement in FEV1 with beta-agonist therapy Relative or absolute contraindication to beta-blocker therapy Exposure to any investigational drugs within the previous 30 days Patients with any concurrent disease or condition, which in the judgment of the investigator would make the patient inappropriate for participation in the study were excluded from this study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Metoprolol-succinate-ER 25mg daily weeks 0-2, 50mg daily weeks 2-4, 100mg daily weeks 4-6, 200mg daily weeks 6-8, 100mg daily week 9, 50mg daily week 10 Carvedilol 3.125mg twice daily weeks 10-12, 6.25mg twice daily weeks 12-14, 12.5mg twice daily weeks 14-16, 25mg twice daily weeks 16-18 | Drug: Metoprolol succinate ER<br>* Cardioselective beta-blocker<br>Drug: Carvedilol<br>* Non-cardioselective beta-blocker<br>|
| Active Comparator: Sequence 2<br>Carvedilol 3.125mg twice daily weeks 0-2, 6.25mg twice daily weeks 2-4, 12.5mg twice daily weeks 4-6, 25mg twice daily weeks 6-8, 12.5mg twice daily week 9, 6.25mg twice daily week 10 Metoprolol-succinate-ER 25mg daily weeks 10-12, 50mg daily weeks 12-14, 100mg daily weeks 14-16, 200mg daily weeks 16-18 | Drug: Metoprolol succinate ER<br>* Cardioselective beta-blocker<br>Drug: Carvedilol<br>* Non-cardioselective beta-blocker<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in FEV1 |  | 0, 4, 8, 14, 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean dose | Mean dose of beta-blocker achieved during low (weeks 0-4 and 10-14) and high (weeks 4-8, 14-18) treatment period | 0-4, 4-8, 10-14, 14-18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-Blocker, Chronic Obstructive Pulmonary Disease, COPD, Cardioselective