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

Sponsor

Erasme University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT05927155

Collaborator

(none)

Enrollment

Location

Arms

9.5

Actual Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: LABA Drug: LAMA	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

A prospective, clinical, uncontrolled, single-blind, cross-over trial that included 2 visits over 2-3 days. Assessments were performed before and after long-acting bronchodilation (LABD): during the first visit, before, 30 minutes and 2 hours after inhalation 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).A prospective, clinical, uncontrolled, single-blind, cross-over trial that included 2 visits over 2-3 days. Assessments were performed before and after long-acting bronchodilation (LABD): during the first visit, before, 30 minutes and 2 hours after inhalation 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).

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Jun 15, 2021

Actual Primary Completion Date :

Mar 30, 2022

Actual Study Completion Date :

Mar 30, 2022

Arms and Interventions

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: Olodaterol Striverdi Respimat
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: Tiotropium Spiriva Respimat

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:

Olodaterol

Striverdi Respimat

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:

Tiotropium

Spiriva Respimat

Outcome Measures

Primary Outcome Measures

Tissue oxygenation (TcO2) change from baseline [120 minutes post-drug-administration]
Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter
Tissue oxygenation (TcO2) change from baseline [30 (LABA)/40 (LAMA) minutes post-drug administration]
Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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