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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05927155
• Other study ID #: SRB-201903-052
• Secondary ID: P2019/239 CCB: B
• Status: Completed
• Phase: Phase 3
• Start date: June 15, 2021
• Est. completion date: March 30, 2022

Study information

• Verified date: June 2023
• Source: Erasme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 30, 2022
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• LABA
Inhalation of 4 puffs of 2,5 µg of a long-acting beta2-agonist (LABA-olodaterol) administered via a spacer device
• LAMA
Inhalation of 4 puffs of 2,5 µg of a long-acting muscarinic antagonist (LAMA-tiotropium) administered via a spacer device

Locations

Country	Name	City	State
Belgium	Erasme University Hospital	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Erasme University Hospital

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tissue oxygenation (TcO2) change from baseline	Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter	120 minutes post-drug-administration
Primary	Tissue oxygenation (TcO2) change from baseline	Transcutaneous oxygen (TcO2) evaluated continuously with a transcutaneous oximeter	30 (LABA)/40 (LAMA) minutes post-drug administration
Secondary	Slope of Helium (SHe) change from baseline	SHe from single-breath washout test (SBWO) assessing peripheral ventilation heterogeneities	120 minutes post-drug administration
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Resonant frequency (Fres) change from baseline	Fres from forced oscillation test (FOT) also evaluating the peripheral lung function	120 minutes post-drug administration
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Forced Expiratory Volume in 1 Second (FEV1) change from baseline	FEV1 from spirometry	120 minutes post-drug administration
Secondary	Forced Expiratory Volume in 1 Second (FEV1) change from baseline	FEV1 from spirometry	30 (LABA)/40 (LAMA) minutes post-drug administration