Inhaled Corticosteroids (ICS) on Pulmonary Endothelial Function in COPD

Study Overview
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Brief Summary
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The study objective is to determine whether an ICS added for 4 weeks to a baseline treatment with a Long-Acting Beta-adrenergic Agonist (LABA) and Long-Acting Muscarinic Antagonist (LAMA) combination improves pulmonary vascular endothelial function as assessed by the vasodilator response to inhaled albuterol (endothelium-dependent vasodilation) in stable COPD patients treated with a LABA/LAMA without an ICS for at least one month.

Official Title
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The Effect of Inhaled Corticosteroids (ICS) Adjunct Therapy on Pulmonary Vascular Endothelial Function in Chronic Obstructive Pulmonary Disease (COPD): Comparison of Two Standard Treatments (NCT05607719

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Bevespi
* Drug: Bretzri


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: physician diagnosis of COPD former smoking history of more than 10 pack-years baseline post-bronchodilator one-second forced expiratory volume (FEV1) 50-80% of predicted, baseline FEV1 and forced vital capacity (FVC) ratio <0.7 males and females, 40-80 years of age regular use of a LAMA/LABA drug regimen for at least a month Exclusion Criteria: women of childbearing potential who do not use accepted birth- control measures pregnant and breast-feeding women respiratory infection within 4 weeks of a test day a Corona Virus Disease (COVID) vaccination <3 months prior to study entry ICS use (within 4 weeks of study entry) ICS hypersensitivity albuterol intolerance use of beta-blocker medication (oral and ophthalmic) use of systemic glucocorticosteroid medication within 6 wk prior to the screening visit an acute COPD exacerbation within 6 wk of the screening day (defined as a need for antibiotic or systemic glucocorticoid therapy or emergency department (ED) visit/hospitalization) current smoking or vaping tobacco or other products Oxygen (O2) saturation of <90% at-rest breathing room air Long-term oxygen therapy (LTOT) required at rest regular use of pulmonary vasodilators systemic arterial systolic pressure >150 mmHg and diastolic pressure >100 mmHg on the test day a >40mmHg right ventricular systolic pressure (RVSP) by prior echocardiography a documented COVID infection within 4 weeks of the screening day Regular use of home oxygen at rest Physician diagnosis of obesity hypoventilation syndrome

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bretzri followed by Bevespi Group<br>Participants in this group will receive Bretzri for 4-weeks followed by 8-weeks of Bevespi. | Drug: Bevespi<br>* Two puffs twice a day<br>Drug: Bretzri<br>* Two puffs twice a day<br>|
| Experimental: Bevespi followed by Bretzri Group<br>Participants in this group will receive Bevespi for 8-weeks followed by 4-weeks of Bretzri. | Drug: Bevespi<br>* Two puffs twice a day<br>Drug: Bretzri<br>* Two puffs twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albuterol induced percent change in pulmonary vascular resistance (PVR) | Echocardiographic assessment of PVR before and after inhalation of 180 μg albuterol as a test of endothelial function | baseline to 15 minutes post inhalation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albuterol induced absolute change in PVR | Echocardiographic assessment of PVR before and after inhalation of 180 μg albuterol as a test of endothelial function | baseline, up to 45 minutes post inhalation | 
| Percent change in FEV1 | Percent change in FEV1 will be measured using spirometry | baseline to 15 minutes post inhalation | 
| Change in oxygen saturation | Change in oxygen saturation measured by pulse oximetry | baseline, up to 45 minutes post inhalation |