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Randomized Controlled Trial
. 2016 Apr;194(2):259-66.
doi: 10.1007/s00408-015-9839-y. Epub 2016 Jan 13.

Effects of Adding Tiotropium or Aclidinium as Triple Therapy Using Impulse Oscillometry in COPD

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Free PMC article
Randomized Controlled Trial

Effects of Adding Tiotropium or Aclidinium as Triple Therapy Using Impulse Oscillometry in COPD

Arvind Manoharan et al. Lung. .
Free PMC article

Abstract

Introduction: Long-acting muscarinic antagonists confer improvements in spirometry when used in addition to inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) in COPD. The dual objectives of this proof of concept study were to evaluate trough effects of tiotropium (TIO) or aclidinium (ACL) when used as triple therapy and to assess if impulse oscillometry (IOS) might be more sensitive than spirometry in detecting subtle differences in bronchodilator response.

Methods: Patients with moderate to severe COPD already taking ICS/LABA were randomized to receive add-on therapy in cross-over fashion with either TIO 18 µg od or ACL 322 µg bid for 2-3 weeks each. Measurements of IOS, spirometry, 6-min walk test, St George's Respiratory Questionnaire (SGRQ) and Baseline/Transition Dyspnoea Index (TDI) were made at baseline and after chronic dosing at trough (12 h for ACL and 24 h for TIO), in addition to domiciliary diurnal spirometry.

Results: 13 patients were completed: mean age 69 years, FEV1 52 % predicted, FEV1/FVC 0.48, and R5 202 % predicted. There were no differences in any visit-based trough IOS or spirometry outcomes comparing TIO versus ACL. Resonant frequency but not total airway resistance at 5 Hz (R5) significantly improved from baseline with both treatments while peripheral airway resistance (R5-R20) significantly improved with ACL. Visit-based FEV1, and forced and relaxed vital capacity were also significantly improved from baseline with both treatments. There were no significant differences in diurnal FEV1 and FEV6 profiles between treatments. 6-min walk distance and post-walk fatigue significantly improved from baseline with ACL, while post-walk dyspnea improved with TIO. SGRQ symptom score significantly improved to a similar degree with both treatments. TDI significantly improved with ACL versus TIO by 1.54 units.

Conclusion: We observed comparable bronchodilator efficacy at trough with TIO and ACL when used as triple therapy in COPD, while IOS was no more sensitive than spirometry.

Keywords: Aclidinium; COPD; Impulse oscillometry; Spirometry; Tiotropium.

Figures

Fig. 1
Fig. 1
After a 1- to 2-week run-in, patients received either tiotropium 18 µg od or aclidinium 322 µg bid for 2–3 weeks each with a 1- to 2-week wash-out in between. Baseline values were measured at Visit 1/3 and after chronic dosing at Visit 2/4
Fig. 2
Fig. 2
CONSORT diagram showing the flow of participants through the study
Fig. 3
Fig. 3
Effects on impulse oscillometry outcomes at baseline and post-treatment with either tiotropium or aclidinium. Data are depicted for individuals as well as means and SEM. a R5 total airway resistance b R5–R20 peripheral airway resistance c RF resonant frequency. There were significant improvements from baseline in RF with aclidinium (P < 0.05) and tiotropium (P < 0.01), and in R5–20 with tiotropium (P < 0.05). There were no significant differences between tiotropium and aclidinium in any oscillometry outcomes
Fig. 4
Fig. 4
Effects on spirometry outcomes at baseline and post-treatment with either tiotropium or aclidinium. Data are depicted for individuals as well as means and SEM. a FEV 1 forced expiratory volume in 1 s b FVC forced vital capacity c RVC relaxed vital capacity. There were significant improvements from baseline for FEV1 within aclidinium (P < 0.01) and tiotropium (P < 0.0001), for FVC within aclidinium (P < 0.05) and tiotropium (P < 0.01), and for RVC within aclidinium (P < 0.0001) and tiotropium (P < 0.05). There were no significant differences between tiotropium and aclidinium in any spirometry outcomes
Fig. 5
Fig. 5
Diurnal profiles with either tiotropium given once daily in the morning or aclidinium given twice daily in the morning and evening, for the last week of each randomized treatment. Data are depicted as means and SEM. a FEV 1 forced expiratory volume in 1 s b FEV 6 forced expiratory volume in 6 s. Data are shown for the morning trough measurement (i.e., pre-dose for aclidinium and tiotropium), 2 and 12 h post dose (i.e., trough for aclidinium), and 2 h post the evening dose of aclidinium or 14 h after the morning dose of tiotropium. There were no significant differences between tiotropium and aclidinium at any time points

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