Tolerability of Metoprolol-Succinate-ER and Carvedilol in COPD

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive; Asthma; Adverse Effect of Beta-adrenoreceptor Antagonists
• Intervention / Treatment: Drug: Metoprolol succinate ER; Drug: Carvedilol

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90073
      • VA West Los Angeles Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; 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; Cardioselective beta-blocker; Drug: Carvedilol; Non-cardioselective beta-blocker
Active Comparator: Sequence 2; 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; Cardioselective beta-blocker; Drug: Carvedilol; Non-cardioselective beta-blocker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: VA Greater Los Angeles Healthcare System
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Freny V Mody, MD, VA Greater Los Angeles Healthcare System

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: December 20, 2016
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: December 7, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Beta-Blocker; Cardioselective
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Metoprolol; Carvedilol
• Other Study ID Numbers: 0027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No