Effects of Acute Long-acting Bronchodilation on Oxygenation and Peripheral Ventilation in COPD

Comparison of Bronchodilation and Oxygenation Patterns Induced by Long-acting β2-agonists and Muscarinic Antagonists in Chronic Obstructive Pulmonary Disease (COPD)

The goal of this clinical trial was to compare the action of long-acting ß2-agonists (LABA-olodaterol) and muscarinic antagonists (LAMA-tiotropium) on tissue oxygenation in COPD considering their impact on proximal and peripheral ventilation and, eventually, on lung capillary volume. The hypothesis was that LABA would have a more peripheral effect than LAMA (due to the opposite gradient of their receptors) and better peripheral ventilation would result in a greater oxygenation.

Before and after LABA (visit 1) and LAMA (visit 2) inhalation, COPD participants were asked to perform single-breath washout and forced oscillation tests, double diffusion technique and spirometry, while transcutaneous oxygenation was continuously recorded.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: LABA; Drug: LAMA

Detailed Description

Slopes of He (SHe) and SF6 (SSF6) from single-breath washout test (SBWO) (assessing ventilation heterogeneities at the level of pre- and intra-acinar bronchioles, respectively) (quadruple model, LR6000 Logan-Sinclair, Rochester, UK), respiratory system resistance (R5, R5-R19) and reactance (X5, AX, Fres) from forced oscillation test (FOT) (Resmon Pro, ResTech, Italy), lung capillary volume (Vc) from double diffusion of NO and CO (DLNO/DLCO) (Hyp'Air compact, Medisoft, Dinant, Belgium), and FEV1 from spirometry (Zan®, Oberthulba, Germany) were evaluated before and after LABD administered via a spacer device: during the first visit, before, 30 minutes and 2 hours after inhalation of 4 puffs of 2,5 µg of olodaterol (LABA); during the second visit, before, 40 minutes and 2 hours after the administration of 4 puffs of 2,5 µg of tiotropium (LAMA). Transcutaneous oximetry (Perimed232©, Järfälla, Sweden) was monitored continuously during the 2 hours of each visit.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Erasme University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• COPD diagnosis according to international criteria

Exclusion Criteria:

• inability to perform the tests or to maintain the washout period
• an exacerbation within the previous 6 weeks
• a diagnosis of asthma or another chronic respiratory disease that could influence the results of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LABA (olodaterol); After 4-5 days washout period, during the first visit, participants received a long-acting beta2-agonist (LABA)	Drug: LABA; Inhalation of 4 puffs of 2,5 µg of a long-acting beta2-agonist (LABA-olodaterol) administered via a spacer device; Other Names: Striverdi Respimat; Olodaterol
Experimental: LAMA (tiotropium); Two days after the first visit, during the second visit , participants received a long-acting muscarinic antagonist (LAMA)	Drug: LAMA; Inhalation of 4 puffs of 2,5 µg of a long-acting muscarinic antagonist (LAMA-tiotropium) administered via a spacer device; Other Names: Spiriva Respimat; Tiotropium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue oxygenation (TcO2) change from baseline	Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter	120 minutes post-drug-administration
Tissue oxygenation (TcO2) change from baseline	Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter	30 (LABA)/40 (LAMA) minutes post-drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slope of Helium (SHe) change from baseline	SHe from single-breath washout test (SBWO) assessing peripheral ventilation heterogeneities	120 minutes post-drug administration
Slope of Helium (SHe) change from baseline	SHe from single-breath washout test (SBWO) assessing peripheral ventilation heterogeneities	30 (LABA)/40 (LAMA) minutes post-drug administration
Area under reactance curve from 5 Hz (AX) change from baseline	AX from forced oscillation test (FOT) evaluating the peripheral lung function	120 minutes post-drug administration
Area under reactance curve from 5 Hz (AX) change from baseline	AX from forced oscillation test (FOT) evaluating the peripheral lung function	30 (LABA)/40 (LAMA) minutes post-drug administration
Reactance at 5 Hz (X5) change from baseline	X5 from forced oscillation test (FOT) also evaluating the peripheral lung function	30 (LABA)/40 (LAMA) minutes post-drug administration
Resonant frequency (Fres) change from baseline	Fres from forced oscillation test (FOT) also evaluating the peripheral lung function	120 minutes post-drug administration
Resonant frequency (Fres) change from baseline	Fres from forced oscillation test (FOT) also evaluating the peripheral lung function	30 (LABA)/40 (LAMA) minutes post-drug administration
Peripheral resistance (R5-R19) change from baseline	Peripheral resistance, assessed as frequency dependence of resistance (R5-R19) from forced oscillation test (FOT) also evaluating the peripheral lung function	120 minutes post-drug administration
Peripheral resistance (R5-R19) change from baseline	Peripheral resistance, assessed as frequency dependence of resistance (R5-R19) from forced oscillation test (FOT) also evaluating the peripheral lung function	30 (LABA)/40 (LAMA) minutes post-drug administration
Lung capillary volume (Vc) change from baseline	Vc from single-breath double diffusion technique of nitric oxide (NO) and carbon monoxide (CO) (DLNO/DLCO)	120 minutes post-drug administration
Lung capillary volume (Vc) change from baseline	Vc from single-breath double diffusion technique of nitric oxide (NO) and carbon monoxide (CO) (DLNO/DLCO)	30 (LABA)/40 (LAMA) minutes post-drug administration
Forced Expiratory Volume in 1 Second (FEV1) change from baseline	FEV1 from spirometry	120 minutes post-drug administration
Forced Expiratory Volume in 1 Second (FEV1) change from baseline	FEV1 from spirometry	30 (LABA)/40 (LAMA) minutes post-drug administration

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Investigators: Principal Investigator: Silvia Pérez Bogerd, MD, Erasme University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2021
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: June 10, 2023
• First Submitted That Met QC Criteria: June 23, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 23, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: oxygen; small airways; gas exchange; long-acting muscarinic antagonist; long-acting ß2-agonist; lung capillary volume
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Lung Diseases, Obstructive; Chronic Disease; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Olodaterol
• Other Study ID Numbers: SRB-201903-052; P2019/239 CCB: B406201939717 (Other Identifier: local ethics committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: When published, the datasets used and/or analysed during the study will be available from the corresponding author on reasonable request.
• IPD Sharing Time Frame: After the publication of the results
• IPD Sharing Access Criteria: The datasets used and/or analysed during the study will be available from the corresponding author on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No