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

Peter A. Frith; Philip J. Thompson; Rajeev Ratnavadivel; Catherina L. Chang; Peter Bremner; Peter Day; Christina Frenzel; Nicol Kurstjens; Glisten Study Group

doi:10.1136/thoraxjnl-2014-206670

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

Peter A. Frith, Philip J. Thompson, Rajeev Ratnavadivel, Catherina L. Chang, Peter Bremner, Peter Day, Christina Frenzel, Nicol Kurstjens, Glisten Study Group

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 μg, once-daily tiotropium (TIO) 18 μg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 μg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV₁ after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results: 773 patients (mean FEV₁ 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO +SAL/FP for trough FEV₁: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV₁ with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St. George's Respiratory Questionnaire total score versus PLA +SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO +SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.

Original language	English
Pages (from-to)	519-527
Number of pages	9
Journal	Thorax
Volume	70
Issue number	6
DOIs	https://doi.org/10.1136/thoraxjnl-2014-206670
Publication status	Published - Jun 2015
Externally published	Yes

Bibliographical note

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Keywords

COPD
LAMA
inhaled corticosteroid (ICS)

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Ratnavadivel_Glycopyrronium_P2015Final published version, 1.11 MBLicence: CC BY-NC

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Frith, P. A., Thompson, P. J., Ratnavadivel, R., Chang, C. L., Bremner, P., Day, P., Frenzel, C., Kurstjens, N., & 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. https://doi.org/10.1136/thoraxjnl-2014-206670

@article{b6128ab5c74c4ad2a53128a41d4e4d53,

title = "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",

abstract = "Background: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 μg, once-daily tiotropium (TIO) 18 μg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 μg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results: 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO +SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St. George's Respiratory Questionnaire total score versus PLA +SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO +SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.",

keywords = "COPD, LAMA, inhaled corticosteroid (ICS)",

author = "Frith, {Peter A.} and Thompson, {Philip J.} and Rajeev Ratnavadivel and Chang, {Catherina L.} and Peter Bremner and Peter Day and Christina Frenzel and Nicol Kurstjens and {Glisten Study Group} and Ainslie Waddell and Alexander Daniel and Alireza Khoussousi and Andrew Springfield and Andrew Veale and Graham, {Anthony Neil} and Brad Gallagher and Pande, {Braj Raj} and Brendan O'Kane and Christopher Jones and Claudio Baldi and Colin Helm and Conor O'Dochartaigh and Daniel Chambers and Dean Quinn and Derek Yull and Dhanalakshi Karthigesu and Edward Then and Frank Graham and Fred Faigenbaum and Geetha Geddam and Gillian Cameron and Hans Blom and Hershel Goldman and Hilary Snell and Imagard Chia and James Jeong and James Liew and James Salvaris and Jason Pryke and Jim Reid and John Kolbe and John O'Sullivan and John Pak and John Upham and Joseph Feiber and Ford, {Judith O.Malley} and Kevin Yong and Kyle Perrin and Lawrence Noonan and Len Atlas and Louise Murdoch and Margaret Pearce and Mark Bloch and Mark Holmes and Michael Chia and Michael Epton and Michelle Leadston and Tandon, {M. K.} and Mohan Chitgopeker and Naomi Liebenberg and Neil Hendry and Olakunle Olaniyi and Omesh Singh and Peter Kendall and {Van Niekerk}, Peter and Rodney Willet and Ronald Tomlins and Salven Pillay and Sammy Sharifeh and Simon Carson and Stephen Bingham and Ted Walford and Tersia Erasmus and Trevor Claridge and Zofia Hess",

note = "This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/",

year = "2015",

month = jun,

doi = "10.1136/thoraxjnl-2014-206670",

language = "English",

volume = "70",

pages = "519--527",

journal = "Thorax",

issn = "0040-6376",

publisher = "British Medical Journal Publishing Group",

number = "6",

}

Frith, PA, Thompson, PJ, Ratnavadivel, R, Chang, CL, Bremner, P, Day, P, Frenzel, C, Kurstjens, N & 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, vol. 70, no. 6, pp. 519-527. https://doi.org/10.1136/thoraxjnl-2014-206670

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. / Frith, Peter A.; Thompson, Philip J.; Ratnavadivel, Rajeev et al.

In: Thorax, Vol. 70, No. 6, 06.2015, p. 519-527.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD

T2 - The GLISTEN study - A randomised controlled trial

AU - Frith, Peter A.

AU - Thompson, Philip J.

AU - Ratnavadivel, Rajeev

AU - Chang, Catherina L.

AU - Bremner, Peter

AU - Day, Peter

AU - Frenzel, Christina

AU - Kurstjens, Nicol

AU - Glisten Study Group

AU - Waddell, Ainslie

AU - Daniel, Alexander

AU - Khoussousi, Alireza

AU - Springfield, Andrew

AU - Veale, Andrew

AU - Graham, Anthony Neil

AU - Gallagher, Brad

AU - Pande, Braj Raj

AU - O'Kane, Brendan

AU - Jones, Christopher

AU - Baldi, Claudio

AU - Helm, Colin

AU - O'Dochartaigh, Conor

AU - Chambers, Daniel

AU - Quinn, Dean

AU - Yull, Derek

AU - Karthigesu, Dhanalakshi

AU - Then, Edward

AU - Graham, Frank

AU - Faigenbaum, Fred

AU - Geddam, Geetha

AU - Cameron, Gillian

AU - Blom, Hans

AU - Goldman, Hershel

AU - Snell, Hilary

AU - Chia, Imagard

AU - Jeong, James

AU - Liew, James

AU - Salvaris, James

AU - Pryke, Jason

AU - Reid, Jim

AU - Kolbe, John

AU - O'Sullivan, John

AU - Pak, John

AU - Upham, John

AU - Feiber, Joseph

AU - Ford, Judith O.Malley

AU - Yong, Kevin

AU - Perrin, Kyle

AU - Noonan, Lawrence

AU - Atlas, Len

AU - Murdoch, Louise

AU - Pearce, Margaret

AU - Bloch, Mark

AU - Holmes, Mark

AU - Chia, Michael

AU - Epton, Michael

AU - Leadston, Michelle

AU - Tandon, M. K.

AU - Chitgopeker, Mohan

AU - Liebenberg, Naomi

AU - Hendry, Neil

AU - Olaniyi, Olakunle

AU - Singh, Omesh

AU - Kendall, Peter

AU - Van Niekerk, Peter

AU - Willet, Rodney

AU - Tomlins, Ronald

AU - Pillay, Salven

AU - Sharifeh, Sammy

AU - Carson, Simon

AU - Bingham, Stephen

AU - Walford, Ted

AU - Erasmus, Tersia

AU - Claridge, Trevor

AU - Hess, Zofia

N1 - This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

PY - 2015/6

Y1 - 2015/6

N2 - Background: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 μg, once-daily tiotropium (TIO) 18 μg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 μg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results: 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO +SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St. George's Respiratory Questionnaire total score versus PLA +SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO +SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.

AB - Background: The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear. The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Methods: This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 μg, once-daily tiotropium (TIO) 18 μg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 μg twice daily. The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks. An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone. Results: 773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial. At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO +SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) -7 mL (SE 17.4) with a lower limit for non-inferiority of -60 mL. There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001). At 12 weeks, GLY+SAL/FP produced significant improvement in St. George's Respiratory Questionnaire total score versus PLA +SAL/FP (LSMdiff -2.154, p=0.02). GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff -0.72 puffs/day, p<0.001). Serious adverse events were similar for GLY+SAL/FP, TIO +SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively. Conclusions: GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP. Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.

KW - COPD

KW - LAMA

KW - inhaled corticosteroid (ICS)

UR - http://www.scopus.com/inward/record.url?scp=84933524786&partnerID=8YFLogxK

U2 - 10.1136/thoraxjnl-2014-206670

DO - 10.1136/thoraxjnl-2014-206670

M3 - Article

C2 - 25841237

AN - SCOPUS:84933524786

SN - 0040-6376

VL - 70

SP - 519

EP - 527

JO - Thorax

JF - Thorax

IS - 6

ER -

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

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