Clinical trial NCT05927155: Effects of Acute Long-acting Bronchodilation on Oxygenation and Peripheral Ventilation in COPD
Official title: Comparison of Bronchodilation and Oxygenation Patterns Induced by Long-acting β2-agonists and Muscarinic Antagonists in Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: long-acting ß2-agonist
long-acting muscarinic antagonist
gas exchange
oxygen
small airways
lung capillary volume
Lead sponsor: Erasme University Hospital
Sponsor class: OTHER
First posted: 2023-07-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
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).
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Tissue oxygenation (TcO2) change from baseline
timeFrame: 120 minutes post-drug-administration
measure: Tissue oxygenation (TcO2) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
Secondary outcomes:
measure: Slope of Helium (SHe) change from baseline
timeFrame: 120 minutes post-drug administration
measure: Slope of Helium (SHe) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
measure: Area under reactance curve from 5 Hz (AX) change from baseline
timeFrame: 120 minutes post-drug administration
measure: Area under reactance curve from 5 Hz (AX) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
measure: Reactance at 5 Hz (X5) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
measure: Resonant frequency (Fres) change from baseline
timeFrame: 120 minutes post-drug administration
measure: Resonant frequency (Fres) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
measure: Peripheral resistance (R5-R19) change from baseline
timeFrame: 120 minutes post-drug administration
measure: Peripheral resistance (R5-R19) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
measure: Lung capillary volume (Vc) change from baseline
timeFrame: 120 minutes post-drug administration
measure: Lung capillary volume (Vc) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
measure: Forced Expiratory Volume in 1 Second (FEV1) change from baseline
timeFrame: 120 minutes post-drug administration
measure: Forced Expiratory Volume in 1 Second (FEV1) change from baseline
timeFrame: 30 (LABA)/40 (LAMA) minutes post-drug administration
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Erasme University Hospital
Study officials:
affiliation: Erasme University Hospital
name: Silvia Pérez Bogerd, MD
role: PRINCIPAL_INVESTIGATOR
References: