Evidence Based Research on Indacaterol–Glycopyrronium for COPD Patients

This article reviews the effectiveness and efficiency of the dual bronchodilator Indacaterol–Glycopyrronium over the regular treatment with salmeterol–fluticasone (SFC) for COPD patients. It includes a PICOT analysis, evaluation of research, research topic, review of literature, recommendation for future research, and annotated bibliography.

Running head: EVIDENCE BASED RESEARCH
Evidence based research
Name of the student:
Name of the university:
Author note:

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EVIDENCE BASED RESEARCH
Table of Contents
PICO:..........................................................................................................................................2
Research question:.....................................................................................................................2
Evaluation of research:...............................................................................................................2
Research topic:...........................................................................................................................3
Review of literature:...................................................................................................................4
Recommendation Future Research:...........................................................................................6
Annotated bibliography:.............................................................................................................7
References:.................................................................................................................................9

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PICOT:
PICO:
Population COPD patients with moderate to severe exacerbations
Intervention Administration of Indacaterol–Glycopyrronium
Comparison No usage of Indacaterol–Glycopyrronium (standard therapy or
placebo)
Outcome Reduced frequency of COPD exacerbation events
Time One year
Research question:
Does the use of Indacaterol–Glycopyrronium in the CIOPD patients as compared to no
usage of Indacaterol–Glycopyrronium within the timeframe of one year reduce the
frequency and severity of COPD exacerbation events?
The research question had been developed utilizingthe PICOT format, where the
COPD patients are the Population, Indacaterol–Glycopyrronium is the chosen Intervention,
not usingIndacaterol–Glycopyrronium is the comparison element, the outcome is reduced
frequency of exacerbation events, and lastly the time frame chosen is the one year interval for
the intervention to work. The research for the paper was done using each phrase in different
combination to find credible and relevant articles from the databases. Only the articles that
are peer reviewed were chosen.
Evaluation of research:
This multicentre, double blind, double-dummy, parallel-group randomized control
trial study had used the dual bronchodilator named the QVA149 which is a fixed dose inhaler
used in combination therapy. Criticizing the study design, the randomized control trials are

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the highest level of evidence along with being a primary research which fits the criteria for
this assignment as well (Bowling, 2014). The double blind and double dummy design for the
study indicates that both the researchers and the participants did not know what they are
being given for the intervention, which limits the chances of bias to a large extent. The dual
bronchodilator intervention of the COPD was compared with the standard treatment of
salmeterol–fluticasone. The process of the data analysis used the effective and efficient SAS
version 9.1. The ethics was upheld by taking the assistance of institutional review boards and
ethics committees at participating centres in accordance with Declaration of Helsinki and
Good Clinical Practice. Data findings indicated a 5% reduction in the incidence rate of COPD
exacerbation events in the patients. The findings had been consistent with the claims made
however there is no mention of the possible strengths and limitation of the study (Vogelmeier
et al., 2013).
Research topic:
The chronic obstructive pulmonary disorder is considered to be one of the most
pressing and emerging type of the lower respiratory disorders that adds a considerable
amount to the disease burden (Tee et al., 2018). The implementation of Indacaterol–
Glycopyrronium treatment has been reported to effectively reduce the frequency and severity
of the exacerbation events drastically (Mahler et al., 2015). This research question therefore
focuses on the effectiveness and efficiency of this particular treatment intervention in
comparison to the regular or standard therapy to reduce the exacerbation event plausibility.
In the statistical data identified that 600,000 people in Australia were living with
COPD with 7,991 deaths caused due to COPD (Health.gov.au, 2018). Hence the disease
burden for this particular condition is extremely high and it also contributes 5% of the total
number of deaths in the Australia. There is need for better and more effective intervention
that can reduce the frequency and severity of the exacerbation events (Frith et al., 2015). The

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dual bronchodilator QVA149 can has previously been reported to show superior efficiency in
reducing the COPD exacerbation likelihood in patients along with having a significant
positive impact on the dyspnoea and activity intolerance for the patients as well improving
the life style quality for patients with moderate to severe COPD as well (Zhong et al., 2015).
Hence, if integrated with the national chronic disease management framework strategies for
treatment, this particular intervention can help in reducing the burden of this diseases for the
Australian demographics significantly (Aihw.gov.au, 2018).
Review of literature:
This primary resource by Vogelmeier et al., (2013) focussed on the effectiveness of
the administration of a dual bronchodilator for the COPD patients in order to reduce the
probability and frequency of the COPD exacerbation events. This randomized control trial by
Vogelmeier et al. (2013) has attempted to discuss the impact of the administration of
indacaterol which is a long- acting β2-agonist with glycopyrronium which a long acting
muscarinic antagonist as a fixed dose of dual bronchodilator on the patients with moderate to
severe COPD exacerbations. The article attempted to research the efficacy, safety, and
tolerability of this intervention to the standard treatment of salmeterol–fluticasone (SFC) for
the intervention of 26 weeks. This research study has incorporated a multicentre, double
blind, double-dummy, parallel-group randomized control trial study design. The benefits of
the double dummy study design is that it is a technique that allowed both of the intervention
to not be identical, which is a commendable strength of the study. Among the 259 patients
that have been selected for participation, the group with QVA149 administration had 55.4%
of overall incidence rate whereas the second intervention group with the regular SFC
treatment had 60.2% incidence rate, which indicates at a considerable 5% reduction in the
adverse event rate in just 26 weeks. Along with that, the article also discusses that the once
daily administration of the QVA149 can effectively provide significant, sustained, and

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clinically meaningful improvements in lung function when compared to the twice daily
administration of the SFC (Vogelmeier et al., 2013). Hence, it can be deduced that the
integration of the dual bronchodilator in standard treatment can effectively reduce the
financial and physical exhaustion of treatment with lesser side effects.
The second primary research article chosen for this review study is by Wedzicha et al.
(2016), which is also a double blind double dummy randomized trail alike the first article
chosen, however, the time limit for this research study has been 52 weeks. This randomized,
double-blind, double-dummy, noninferiority trial attempted to explore the role of treatment
with a LAMA-LABA regimen with the combination of glycopyrronium which is a long
acting beta agonist and indacaterol which is a long-acting muscarinic antagonist. The
sampling for the research study was randomized involving 1680 patients for the indacaterol–
glycopyrronium group and 1682 patients for salmeterol–fluticasone group. The results in this
case indicated that the indacaterolglycopyrronium group took longer time interval for the first
exacerbation event to occur than the comparison group, and the annual risk rate for this group
also represented a 16% lower risk. A novel information this article provided is the fact that
the indacaterol–glycopyrronium intervention group results were also independent of baseline
blood eosinophil count. Although the difference in the total number of adverse events were
similar in both groups, the difference was significant. The incidence of the pneumonia in case
of the indacaterol–glycopyrronium intervention group was 3.2% whereas for the standard
group had been 4.8%. Hence, it can be mentioned that for the COPD patients the intervention
of the indacaterol–glycopyrroniumis more effective (Wedzicha et al., 2016).
The third article chosen by the Zhong et al. (2015) is a LANTERN study, a double-
blind, double-dummy, parallel-group study which had been based on the current global
initiative for the COPD treatment which recommends the use of more than one
bronchodilators with respect to the airflow restrictions of the patient. The participants chosen

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for the study had been 744 patients suffering from moderate to severe COPD with a history of
<1 exacerbations in the last year with 1:1 QVA149 110/50 μg once daily or SFC 50/500 μg
administered :twice daily for 26 week. The time limit in this case also had been 26 weeks,
and the primary end point had been non- inferiority of QVA149 versus SFC for trough forced
expiratory volume in 1 second (FEV1) at week 26. The data findings of this research article is
also consistent with the rest of the two primary sources reviewed with QVA149
demonstrating statistically significant superiority to SFC for trough FEV1. Elaborating on the
data findings, the primary objective set for non-inferiority between the QVA149 and SFC in
trough FEV1 at week 26 was met. QVA149 was found to significantly reduce the rate of
moderate or severe exacerbations by 31%, which aligns successfully with the results revealed
by the previous articles. Along with that, the authors in this research study could also explain
that the rate of pneumonia had also been three times lower for the patients that were
administered QVA149. Hence, it can be concluded that all three primary sources identified
the intervention of QVA149 to have significantly higher superior efficiency in reducing the
exacerbation rate and pneumonia (Zhong et al., 2015). Hence, there is significantly promising
implication of this intervention in future treatment or clinical practice.
Recommendation Future Research:
The review identified three articles that focussed on the effectiveness and efficiency
of the dual bronchodilator QVA149 or indacaterol–glycopyrronium over the regular
treatment with salmeterol–fluticasone (SFC) across different time interventions (Wedzicha et
al., 2017). All three of the articles were successful in proving the superiority of indacaterol–
glycopyrronium over salmeterol–fluticasone in reducing the frequency of exacerbation events
and prolonging the intervals between the events as well. The article by Zhong et al. (2015)
and Wedzicha et al. (2016) has also been able to identify indacaterol–glycopyrronium to
reduce the probability of pneumonia in patients with moderate to severe COPD as well,

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which is a very common complication for COPD. However, neither of the articles
incorporated the cost effectiveness of this intervention at all, which is a very important aspect
for this intervention to be incorporated in the national strategic chronic disease management
framework in large scale clinical practice. Hence. There is need for further research to be
carried out to explore the cost effectiveness of this dual bronchodilator in large scale clinical
practice. The recommended study design in this case is observational cohort study to explore
the financial feasibility of integrating the indacaterol–glycopyrronium in clinical practice
(Green &Thorogood, 2018).

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EVIDENCE BASED RESEARCH
Annotated bibliography:
Vogelmeier, C. F., Bateman, E. D., Pallante, J., Alagappan, V. K., D'Andrea, P., Chen, H.,
&Banerji, D. (2013). Efficacy and safety of once-daily QVA149 compared with
twice-daily salmeterol–fluticasone in patients with chronic obstructive pulmonary
disease (ILLUMINATE): a randomised, double-blind, parallel group study. The
Lancet Respiratory Medicine, 1(1), 51-60. doi: 10.1016/S2213-2600(12)70052-8
This randomized multicentre double-blind, double-dummy, parallel-
group study explored the effectiveness of QVA149 dual bronchodilator over
salmeterol–fluticasone in patients with moderate to severe COPD. The results
indicated Once-daily QVA149 to provide significant, sustained, and clinically
meaningful effects in lung function and limit the likelihood of exacerbations.
Wedzicha, J. A., Banerji, D., Chapman, K. R., Vestbo, J., Roche, N., Ayers, R.
T., ...&Vogelmeier, C. F. (2016). Indacaterol–glycopyrronium versus salmeterol–
fluticasone for COPD. New England Journal of Medicine, 374(23), 2222-2234. doi:
10.1056/nejmoa1516385
This 52-week, randomized, double-blind, double-dummy, noninferiority trial explored
the impact of LABA-LAMA regimen involving the indacaterol–glycopyrronium on the
patients with moderate to severe COPD. The data findings indicated indacaterol–
glycopyrronium to be more effective than the salmeterol–fluticasone in the patients
consistently.
Zhong, N., Wang, C., Zhou, X., Zhang, N., Humphries, M., Wang, L., ...&Banerji, D. (2015).
LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone
combination in patients with COPD. International journal of chronic obstructive
pulmonary disease, 10, 1015. doi: 10.2147/COPD.S84436

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The LANTERN study evaluated the impact of indacaterol–glycopyrronium over
salmeterol–fluticasone in COPD patients taking the study design of double-blind, double-
dummy, parallel-group RCT. The data findings indicated QVA149 to be a potent alternative
treatment over SFC for management of moderate to severe COPD.

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References:
Bowling, A. (2014). Research methods in health: investigating health and health services.
McGraw-Hill Education (UK). Retrieved from https://books.google.co.in/books?
hl=en&lr=&id=6lOLBgAAQBAJ&oi=fnd&pg=PR3&dq=Bowling,+A.+(2014).
+Research+methods+in+health:+investigating+health+and+health+services.
+McGrawHill+Education+
(UK)&ots=YeGe5CdMaI&sig=uAN6n6BODK8r3BdCz34rOVEGlI#v=onepage&q=
Bowling%2C%20A.%20(2014).%20Research%20methods%20in%20health%3A
%20investigating%20health%20and%20health%20services.%20McGraw-Hill
%20Education%20(UK)&f=false
Chronic disease Overview - Australian Institute of Health and Welfare. (2018). Retrieved
from-https://www.aihw.gov.au/reports-statistics/health-conditions-disability-deaths/
chronic-disease/overview
Frith, P. A., Thompson, P. J., Ratnavadivel, R., Chang, C. L., Bremner, P., Day, P., ...&
Glisten Study Group. (2015). Glycopyrronium once-daily significantly improves lung
function and health status when combined with salmeterol/fluticasone in patients with
COPD: the GLISTEN study—a randomised controlled trial. Thorax, 70(6), 519-527.
doi: 10.1136/thoraxjnl-2014-206670
Green, J., &Thorogood, N. (2018). Qualitative methods for health research. Sage. Retrieved
from https://books.google.co.in/books?
hl=en&lr=&id=HUhLDwAAQBAJ&oi=fnd&pg=PP1&dq=Green,+J.,+
%26Thorogood,+N.+(2018).+Qualitative+methods+for+health+research.
+Sage.&ots=quEaXPMbTN&sig=tAfLwNfOP2ydQ4beCJZAfAzSwHs#v=onepage&
q&f=false

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EVIDENCE BASED RESEARCH
Health.gov.au. (2018). Department of Health | National Strategic Framework for Chronic
Conditions. [online] Available at:
http://www.health.gov.au/internet/main/publishing.nsf/content/nsfcc [Accessed 30
Sep. 2018].
Mahler, D., Keininger, D., Fogel, R., Mezzi, K., &Banerji, D. (2015). QVA149 is more
efficacious than tiotropium and salmeterol/fluticasone combination (SFC) in
improving patient-reported outcomes and lung function in COPD patients with
moderate-to-severe baseline dyspnoea: The IGNITE trials. doi:
10.1183/13993003.congress-2015.PA2966
Tee, A., Chow, W. L., Burke, C., &Guruprasad, B. (2018). Cost-effectiveness of
indacaterol/glycopyrronium in comparison with salmeterol/fluticasone combination
for patients with moderate-to-severe chronic obstructive pulmonary disease: a
LANTERN population analysis from Singapore. Singapore medical journal, 59(7),
383. doi: 10.11622/smedj.2018022
Vogelmeier, C. F., Bateman, E. D., Pallante, J., Alagappan, V. K., D'Andrea, P., Chen, H.,
&Banerji, D. (2013). Efficacy and safety of once-daily QVA149 compared with
twice-daily salmeterol–fluticasone in patients with chronic obstructive pulmonary
disease (ILLUMINATE): a randomised, double-blind, parallel group study. The
Lancet Respiratory Medicine, 1(1), 51-60. doi: 10.1016/S2213-2600(12)70052-8
Wedzicha, J. A., Banerji, D., Chapman, K. R., Vestbo, J., Roche, N., Ayers, R.
T., ...&Vogelmeier, C. F. (2016). Indacaterol–glycopyrronium versus salmeterol–
fluticasone for COPD. New England Journal of Medicine, 374(23), 2222-2234. doi:
10.1056/nejmoa1516385

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Wedzicha, J. A., Zhong, N., Ichinose, M., Humphries, M., Fogel, R., Thach, C., ...&Banerji,
D. (2017). Indacaterol/glycopyrronium versus salmeterol/fluticasone in Asian patients
with COPD at a high risk of exacerbations: results from the FLAME
study. International journal of chronic obstructive pulmonary disease, 12, 339. doi:
10.2147/COPD.S125058
Zhong, N., Wang, C., Zhou, X., Zhang, N., Humphries, M., Wang, L., ...&Banerji, D. (2015).
LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone
combination in patients with COPD. International journal of chronic obstructive
pulmonary disease, 10, 1015. doi: 10.2147/COPD.S84436
Zhong, N., Wang, C., Zhou, X., Zhang, N., Patalano, F., Humphries, M., ...&Banerji, D.
(2015). C22 I FEEL FINE NOW: NEW TREATMENTS FOR COPD: Qva149
Significantly Lowers The Rate And Risk Of Moderate Or Severe COPD Exacerbation
Versus Salmeterol/fluticasone In Patients With Moderate To Severe COPD: The
Lantern Study. American Journal of Respiratory and Critical Care Medicine, 191, 1.
doi: 10.1164/ajrccm-conference.2015.191.1