Symbicort in Airway Predominant Chronic Obstructive Pulmonary Disease (COPD) (SACOPD)

COPDGene Ancillary Proposal: Symbicort Intervention in "Airway Predominant

The main objective of the study is to see if using anti-inflammatory to patients with airway disease chronic obstructive pulmonary disease (COPD) phenotype will be more effective than using these treatments in patients with loss of lung tissue. Symbicort plus ipratropium/albuterol will be used for 12 weeks in an open-label study in subjects with airway predominant COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Ipratropium/albuterol; Drug: Budesonide; Drug: budesonide/formoterol

Detailed Description

Subjects from the COPDGene study who have airway-predominant COPD on chest CT scan will be enrolled; a total of 40 subjects is planned.

Subjects will all have background ipratropium-albuterol administered four times daily. Subjects will be randomized to receive budesonide (180 ug twice daily) or formoterol-budesonide (160/4.5 ug twice daily) for 12 weeks.

The main objective is to explore novel outcomes: blood biomarkers and chest CT scan. Outcomes include lung function, walk distance, respiratory disease-specific health status, and expiratory chest CT scan gas trapping as an exploratory outcome.

The primary outcome measure will be FEV1 pre-bronchodilator 12 hours after the last dose of study medication at the end of 12 weeks of treatment. FEV1 will be measured in the morning 6 hours after the last dose of ipratropium/albuterol and 12 hours after the last dose of budesonide and budesonide/formoterol

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham Medical Center
  • California
    • Torrance, California, United States, 90502
      • Harbor Ucla Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Worcester, Massachusetts, United States, 01608
      • Reliant Medical Group
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. COPD GOLD Stage 2 and 3 (post-bronchodilator FEV1 35-80% predicted and FEV1/FVC <0.7 at the time of enrollment in COPDGene) by spirometry.
2. Less than 15% of the lung <-950 Hounsfield Units on COPDGene high-resolution inspiratoryChest CT scan (i.e. no evidence of significant emphysema)
3. Greater than 10% gas trapping on COPDGene expiratory CT scan (i.e. evidence of small airway disease).
4. No history of recent use (within the pat 8 weeks) of an inhaled or systemic corticosteroid.
5. Body weight <100 kg (low dose CT scans in subject with increased boyd weight can not be reliably analyzed).

Exclusion Criteria:

1. Exacerbation of COPD or other respiratory illness requiring antibiotics within the past 8 weeks.
2. Previous adverse reaction to inhaled steroids, long-acting beta agonists, or long-acting anticholinergic medications.
3. Symptomatic, untreated benign prostate hypertrophy.
4. Allergy to peanuts.
5. Glaucoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ipratropium/albuterol; 1 puff 4 times daily	Drug: Ipratropium/albuterol; Inhaled ipratropium/albuterol combination 2 puffs four times daily; Other Names: Combivent®
Experimental: Budesonide; budesonide 180 ug 2 puffs 4 times daily + ipratropium/albuterol 1 puffs four times daily	Drug: Ipratropium/albuterol; Inhaled ipratropium/albuterol combination 2 puffs four times daily; Other Names: Combivent®; Drug: Budesonide; Inhaled budesonide twice daily plus inhaled ipratropium/albuterol combination four times daily and every 4 hours as needed; Other Names: Pulmicort Flexhaler®
Experimental: budesonide/formoterol; budesonide/formoterol 160/4.5 ug 2 puffs 4 times daily + ipratropium/albuterol 1 puffs four times daily	Drug: Ipratropium/albuterol; Inhaled ipratropium/albuterol combination 2 puffs four times daily; Other Names: Combivent®; Drug: budesonide/formoterol; Inhaled budesonide/formoterol (160/4.5 mcg Symbicort®) 2 puffs twice daily plus inhaled ipratropium/albuterol (Combivent®) 1 puff four times daily; Other Names: Symbicort®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced expiratory volume in 1 second (FEV1) pre-bronchodilator	FEV1 will be measured in the morning 6 hours after the last dose of ipratropium/albuterol and 12 hours after the last dose budesonide and budesonide/formoterol	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Status	Administer St. George's Respiratory Questionnaire at randomization and 12 weeks.	12 weeks
Dyspnea	Evaluated by the Modified Medical Research Council Dyspnea Scale at randomization and week 12.	12 weeks
Six minute walk distance	Evaluate six minute walk distance at randomization and 12 weeks	12 weeks
Forced vital capacity (FVC) pre-bronchodilator		12 weeks
Post-bronchodilator FEV1		12 weeks
Patient-reported exacerbations		12 weeks
Patient reported adverse events		12 weeks
Post-bronchodilator FVC		12 weeks
CT scan gas trapping		Before and 12 weeks after randomization

Collaborators and Investigators

• Sponsor: National Jewish Health
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: James D Crapo, MD, National Jewish Health; Principal Investigator: Edwin K Silverman, MD, PhD, Brigham and Women's Hospital; Principal Investigator: Barry J Make, MD, National Jewish Health

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 16, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimate): December 3, 2010

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Budesonide; Albuterol; Ipratropium; Formoterol Fumarate
• Other Study ID Numbers: SYMB0012

Plan for Individual participant data (IPD)

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