Pulmonary Gas Exchange Response to Indacaterol in COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02547558
• Other study ID #: IndaEPOC
• Status: Not yet recruiting
• Phase: Phase 4
• First received: September 4, 2015
• Last updated: September 10, 2015
• Start date: October 2015
• Est. completion date: November 2015

Study information

• Verified date: September 2015
• Source: Hospital Clinic of Barcelona
• Contact: Isabel Blanco, MD, PhD
• Phone: +34 649539835
• Email: IBLANCO2[@]clinic.ub.es
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Procedure:
• Arterial blood gases
Measured through radial arterial catheter
• Cardiac Output
Measured through bioimpedance: FloTrac pressure transducer (FloTrac sensor; Edwards Lifesciences) using the third-generation (3.01) FloTrac software for continuous CO display.
• Vital signs
As measured in clinical practice
• Exhaled breath
Were recorded using a pneumotachograph (CPX/D; Med Graphics, St. Paul, MN, U.S.A.).
• Spirometry
In a daily calibrated spirometer.

Drug:
• Indacaterol
Indacaterol Breezhaler@ 300 mcg (1 inhalation)

Locations

Country	Name	City	State
Spain	Hospital Clínic	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

Country where clinical trial is conducted

Spain, 

References & Publications (11)

Cazzola M, Segreti A, Stirpe E, Puxeddu E, Ora J, Rogliani P, Matera MG. Effect of an additional dose of indacaterol in COPD patients under regular treatment with indacaterol. Respir Med. 2013 Jan;107(1):107-11. doi: 10.1016/j.rmed.2012.09.022. Epub 2012 Oct 18. — View Citation

Gabrijelcic J, Casas A, Rabinovich RA, Roca J, Barberà JA, Chung KF, Rodríguez-Roisin R. Formoterol protects against platelet-activating factor-induced effects in asthma. Eur Respir J. 2004 Jan;23(1):71-5. — View Citation

Kew KM, Dias S, Cates CJ. Long-acting inhaled therapy (beta-agonists, anticholinergics and steroids) for COPD: a network meta-analysis. Cochrane Database Syst Rev. 2014 Mar 26;3:CD010844. doi: 10.1002/14651858.CD010844.pub2. Review. — View Citation

Kew KM, Mavergames C, Walters JA. Long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2013 Oct 15;10:CD010177. doi: 10.1002/14651858.CD010177.pub2. Review. — View Citation

Khoukaz G, Gross NJ. Effects of salmeterol on arterial blood gases in patients with stable chronic obstructive pulmonary disease. Comparison with albuterol and ipratropium. Am J Respir Crit Care Med. 1999 Sep;160(3):1028-30. — View Citation

Pillet O, Manier G, Castaing Y. Anticholinergic versus beta 2-agonist on gas exchange in COPD: a comparative study in 15 patients. Monaldi Arch Chest Dis. 1998 Feb;53(1):3-8. — View Citation

Polverino E, Gómez FP, Manrique H, Soler N, Roca J, Barberà JA, Rodríguez-Roisin R. Gas exchange response to short-acting beta2-agonists in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2007 Aug 15;176(4):350-5. Epub 2007 Apr 12. — View Citation

Roskell NS, Anzueto A, Hamilton A, Disse B, Becker K. Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol. Int J Chron Obstruct Pulmon Dis. 2014 Jul 31;9:813-24. doi: 10.2147/COPD.S59673. eCollection 2014. Review. — View Citation

Viegas CA, Ferrer A, Montserrat JM, Barberà JA, Roca J, Rodriguez-Roisin R. Ventilation-perfusion response after fenoterol in hypoxemic patients with stable COPD. Chest. 1996 Jul;110(1):71-7. Erratum in: Chest 1997 Jan;111(1):258. — View Citation

Whale CI, Sovani MP, Mortimer K, Oborne J, Cooper S, Harrison TW, Tattersfield AE. Effects of rac-albuterol on arterial blood gases in patients with stable hypercapnic chronic obstructive pulmonary disease. Br J Clin Pharmacol. 2006 Aug;62(2):153-7. — View Citation

Zafar MA, Droege C, Foertsch M, Panos RJ. Update on ultra-long-acting ß agonists in chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2014 Dec;23(12):1687-701. doi: 10.1517/13543784.2014.942730. Epub 2014 Aug 19. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in PaO2 after indacaterol.		60 and 120 minutes	No
Secondary	Change in PaCO2 after indacaterol.		60 and 120 minutes	No
Secondary	Change in D(A-a)DO2 after indacaterol.		60 and 120 minutes	No
Secondary	Change in pH after indacaterol.		60 and 120 minutes	No
Secondary	Change in cardiac output after indacaterol.		60 and 120 minutes	No