title: LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD.
abstract: BACKGROUND
  The current Global initiative for chronic Obstructive Lung Disease (GOLD) treatment strategy recommends the use of one or more bronchodilators according to the patient's airflow limitation, their history of exacerbations, and symptoms. The LANTERN study evaluated the effect of the long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator, QVA149 (indacaterol/glycopyrronium), as compared with the LABA/inhaled corticosteroid, salmeterol/fluticasone (SFC), in patients with moderate-to-severe COPD with a history of ≤1 exacerbation in the previous year.
  
  
  METHODS
  In this double-blind, double-dummy, parallel-group study, 744 patients with moderate-to-severe COPD with a history of ≤1 exacerbations in the previous year were randomized (1:1) to QVA149 110/50 μg once daily or SFC 50/500 μg twice daily for 26 weeks. The primary endpoint was noninferiority of QVA149 versus SFC for trough forced expiratory volume in 1 second (FEV1) at week 26.
  
  
  RESULTS
  Overall, 676 patients completed the study. The primary objective of noninferiority between QVA149 and SFC in trough FEV1 at week 26 was met. QVA149 demonstrated statistically significant superiority to SFC for trough FEV1 (treatment difference [Δ]=75 mL; P<0.001). QVA149 demonstrated a statistically significant improvement in standardized area under the curve (AUC) from 0 hours to 4 hours for FEV1 (FEV1 AUC0-4h) at week 26 versus SFC (Δ=122 mL; P<0.001). QVA149 and SFC had similar improvements in transition dyspnea index focal score, St George Respiratory Questionnaire total score, and rescue medication use. However, QVA149 significantly reduced the rate of moderate or severe exacerbations by 31% (P=0.048) over SFC. Overall, the incidence of adverse events was comparable between QVA149 (40.1%) and SFC (47.4%). The incidence of pneumonia was threefold lower with QVA149 (0.8%) versus SFC (2.7%).
  
  
  CONCLUSIONS
  These findings support the use of the LABA/LAMA, QVA149 as an alternative treatment, over LABA/inhaled corticosteroid, in the management of moderate-to-severe COPD patients (GOLD B and GOLD D) with a history of ≤1 exacerbation in the previous year.
authors.affiliation: State Key Laboratory of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: Institute of Respiratory Disease, Xin Qiao Hospital, Third Military Medical University, Chongqing City, Chongqing, People's Republic of China.
authors.forename: Changzheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing City, Chongqing, People's Republic of China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Nuofu
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Beijing Novartis Pharma Co. Ltd., Shanghai, People's Republic of China.
authors.forename: Michael
authors.initials: M
authors.lastname: Humphries
authors.affiliation: Beijing Novartis Pharma Co. Ltd., Shanghai, People's Republic of China.
authors.forename: Linda
authors.initials: L
authors.lastname: Wang
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Chau
authors.initials: C
authors.lastname: Thach
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Patalano
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006024:Glycopyrrolate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009330:Nebulizers and Vaporizers; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020127:Recovery of Function; D012720:Severity of Illness Index; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D005938:Glucocorticoids; D007189:Indans; D018727:Muscarinic Antagonists; D015363:Quinolones; C554862:indacaterol-glycopyrronium combination; D006024:Glycopyrrolate
keywords: COPD; clinical trial; long-acting muscarinic antagonist; long-acting β2-agonists