Pulmonary Gas Exchange Response to Indacaterol in COPD

Study Overview
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Brief Summary
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To evaluate the pulmonary gas exchange response to a therapeutic high dose of inhaled indacaterol (300 mcg) in 20 outpatients with stable symptomatic COPD B and D GOLD 2011 groups. Measurements on a single day before and after 60 and 120 minutes of indacaterol will include arterial PO2, PaCO2 and pH. AaPO2; SaO2 (by pulse oximetry) and oxygen and carbon dioxide in exhaled breath, systemic arterial pressure and heart rate will also be measured/calculated. Cardiac output will be directly measured by bio-impedance.

Detailed Description
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The investigators hypothesize that in stable chronic obstructive pulmonary disease (COPD) patients the interaction between intrapulmonary and extrapulmonary determinants contributing to gas exchange abnormalities after indacaterol will ultimately preserve arterial oxygenation (primary end-point outcome). The study will include 20 outpatients with diagnosis of stable COPD in GOLD 2011 groups B and D (10 each), without frequent exacerbations (≥2 in the previous year). Patients with a COPD exacerbation within 3 months of study, use of long-term oxygen therapy and associated conditions or serious comorbidities (i.e., asthma, bronchiectasis, lung cancer and/or cardiovascular diseases) will be excluded. Each patient will be studied on a single day. All subjects will remain on their regular treatment for the study. Subjects will be required to withhold SABAs for at least 12 h and LABAs and theophylline for at least 24 h before study. During measurements, patients will breath room air and will be seated in an armchair. Measurements will be performed before and 60 and 120 min after a single dose administration of indacaterol Breezhaler@ 300 mcg (1 inhalation). After ensuring steady-state conditions, as assessed by stability (± 5%) of both ventilatory and hemodynamic variables, and by the close agreement (within ± 5%) between duplicate of mixed expired and arterial oxygen and carbon dioxide, a set of duplicate measurements for each variable will be obtained at each time point. Blood samples will be collected through a catheter inserted under local anesthesia into the radial artery. Samples of blood (5 ml) will be removed for measurement of arterial O2 tension (PaO2), CO2 tension (PaCO2) and pH; alveolar-arterial PO2 difference (A-a)DO2, oxygen saturation (SaO2), and VO2, VCO2, Ve, respiratory rate (f), systemic arterial pressure (Psa), and heart rate (HR) will be measured or calculated, as previously described. Cardiac output will be directly measured by bio-impedance. Spirometry values will be recorded from the history records of each patient. All measurements will be performed in the Centre de Diagnòstic Respiratori (CDR), Servei de Pneumologia, Institut del Tòrax, Hospital Clínic, Barcelona. The primary outcome will be the PaO2 change after indacaterol at each analysis time. Based on a previous study in stable severe COPD patients using nebulized salbutamol during convalescence of exacerbation, Polverino et al. calculated that for a significant PaO2 fall of the order of 8 mmHg, a sample of 6 subjects is needed; this number was increased to 20 patients to ensure better data. Secondary outcomes were changes in PaCO2, pH, the calculated D(A-a)DO2 and the response of cardiac output. Results will be expressed as mean (±SEM) or median (95% CI). The effects of indacaterol on each of the end-point variables will be assessed by one-way repeated measures analysis of variance (ANOVA). Paired t tests and Pearson's correlation tests will be used as appropriate. All significances will be set at p<0.05, without correction for multiple tests.

Official Title
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Pulmonary Gas Exchange Response to Indacaterol in Stable Symptomatic Chronic Obstructive Pulmonary Disease Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Procedure: Arterial blood gases
* Procedure: Cardiac Output
* Procedure: Vital signs
* Procedure: Exhaled breath
* Procedure: Spirometry
* Drug: Indacaterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients with COPD diagnosis according to GOLD 2011 criteria (VEF1/CVF less than 70%), groups B and D. Exclusion Criteria: Conditions or serious comorbidities (i.e., asthma, bronchiectasis, lung cancer and/or cardiovascular diseases). Patients with frequent exacerbations (2 or more exacerbations in the past year). History of acute COPD exacerbation in the previous 3 months.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol<br>Drug: -Indacaterol, inhaled, single dose, 300 mcg Diagnostic Interventions: Arterial blood gases Cardiac output Vital signs Exhaled breath Spirometry | Procedure: Arterial blood gases<br>* Measured through radial arterial catheter<br>* Other names: AaPO2;Procedure: Cardiac Output<br>* Measured through bioimpedance: FloTrac pressure transducer (FloTrac sensor; Edwards Lifesciences) using the third-generation (3.01) FloTrac software for continuous CO display.<br>* Other names: CO;Procedure: Vital signs<br>* As measured in clinical practice<br>* Other names: Systemic arterial pressure;Procedure: Exhaled breath<br>* Were recorded using a pneumotachograph (CPX/D; Med Graphics, St. Paul, MN, U.S.A.).<br>* Other names: Carbon dioxide;Procedure: Spirometry<br>* In a daily calibrated spirometer.<br>* Other names: VFC;Drug: Indacaterol<br>* Indacaterol Breezhaler@ 300 mcg (1 inhalation)<br>* Other names: Ultra long acting beta 2 agonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PaO2 after indacaterol. |  | 60 and 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PaCO2 after indacaterol. |  | 60 and 120 minutes | 
| Change in D(A-a)DO2 after indacaterol. |  | 60 and 120 minutes | 
| Change in pH after indacaterol. |  | 60 and 120 minutes | 
| Change in cardiac output after indacaterol. |  | 60 and 120 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Indacaterol, Pulmonary gas exchange, Long-acting bronchodilators