Pulmonary Gas Exchange Response to Indacaterol in COPD

NCT ID: NCT02547558

Last Updated: 2015-09-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2015-11-30

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.

Conditions

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Chronic Obstructive Pulmonary Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Indacaterol

Drug:

-Indacaterol, inhaled, single dose, 300 mcg

Diagnostic Interventions:

* Arterial blood gases
* Cardiac output
* Vital signs
* Exhaled breath
* Spirometry

Group Type EXPERIMENTAL

Arterial blood gases

Intervention Type PROCEDURE

Measured through radial arterial catheter

Cardiac Output

Intervention Type PROCEDURE

Measured through bioimpedance: FloTrac pressure transducer (FloTrac sensor; Edwards Lifesciences) using the third-generation (3.01) FloTrac software for continuous CO display.

Vital signs

Intervention Type PROCEDURE

As measured in clinical practice

Exhaled breath

Intervention Type PROCEDURE

Were recorded using a pneumotachograph (CPX/D; Med Graphics, St. Paul, MN, U.S.A.).

Spirometry

Intervention Type PROCEDURE

In a daily calibrated spirometer.

Indacaterol

Intervention Type DRUG

Indacaterol Breezhaler@ 300 mcg (1 inhalation)

Interventions

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Arterial blood gases

Measured through radial arterial catheter

Intervention Type PROCEDURE

Cardiac Output

Measured through bioimpedance: FloTrac pressure transducer (FloTrac sensor; Edwards Lifesciences) using the third-generation (3.01) FloTrac software for continuous CO display.

Intervention Type PROCEDURE

Vital signs

As measured in clinical practice

Intervention Type PROCEDURE

Exhaled breath

Were recorded using a pneumotachograph (CPX/D; Med Graphics, St. Paul, MN, U.S.A.).

Intervention Type PROCEDURE

Spirometry

In a daily calibrated spirometer.

Intervention Type PROCEDURE

Indacaterol

Indacaterol Breezhaler@ 300 mcg (1 inhalation)

Intervention Type DRUG

Other Intervention Names

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PaO2 PaCO2 pH AaPO2 CO Respiratory rate Heart rate (HR) Systemic arterial pressure Oxygen Carbon dioxide FEV1 VFC Ultra long acting beta 2 agonist

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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Clinic of Barcelona

OTHER

Sponsor Role lead

Responsible Party

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Isabel Blanco

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Isabel Blanco, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clínic

Locations

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Hospital Clínic

Barcelona, , Spain

Site Status

Countries

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Spain

Central Contacts

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Isabel Blanco, MD, PhD

Role: CONTACT

+34 649539835

Facility Contacts

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Isabel Blanco, MD, PhD

Role: primary

+34 649539835

References

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Viegas CA, Ferrer A, Montserrat JM, Barbera JA, Roca J, Rodriguez-Roisin R. Ventilation-perfusion response after fenoterol in hypoxemic patients with stable COPD. Chest. 1996 Jul;110(1):71-7. doi: 10.1378/chest.110.1.71.

Reference Type BACKGROUND
PMID: 8681669 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9632900 (View on PubMed)

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. doi: 10.1111/j.1365-2125.2006.02604.x.

Reference Type BACKGROUND
PMID: 16842389 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 24127118 (View on PubMed)

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;2014(3):CD010844. doi: 10.1002/14651858.CD010844.pub2.

Reference Type BACKGROUND
PMID: 24671923 (View on PubMed)

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. doi: 10.1164/ajrccm.160.3.9812117.

Reference Type BACKGROUND
PMID: 10471636 (View on PubMed)

Zafar MA, Droege C, Foertsch M, Panos RJ. Update on ultra-long-acting beta 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.

Reference Type BACKGROUND
PMID: 25139313 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25114521 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23083839 (View on PubMed)

Gabrijelcic J, Casas A, Rabinovich RA, Roca J, Barbera JA, Chung KF, Rodriguez-Roisin R. Formoterol protects against platelet-activating factor-induced effects in asthma. Eur Respir J. 2004 Jan;23(1):71-5. doi: 10.1183/09031936.03.00057803.

Reference Type BACKGROUND
PMID: 14738234 (View on PubMed)

Polverino E, Gomez FP, Manrique H, Soler N, Roca J, Barbera JA, Rodriguez-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. doi: 10.1164/rccm.200612-1864OC. Epub 2007 Apr 12.

Reference Type BACKGROUND
PMID: 17431221 (View on PubMed)

Other Identifiers

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IndaEPOC

Identifier Type: -

Identifier Source: org_study_id

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