title: The EFFECT trial: evaluating exacerbations, biomarkers, and safety outcomes with two dose levels of fluticasone propionate/formoterol in COPD.
abstract: Inhaled corticosteroid/long-acting β2-agonist combination therapy is recommended in chronic obstructive pulmonary disease (COPD) patients at high risk of exacerbations. The EFFECT (Efficacy of Fluticasone propionate/FormotErol in COPD Treatment) trial is a Phase III, 52-week, randomized, double-blind study to evaluate the efficacy and safety of two doses of fluticasone propionate/formoterol compared to formoterol monotherapy in COPD patients with FEV1 ≥50% predicted and a history of exacerbations. The primary endpoint is the annualized rate of moderate and severe exacerbations. Secondary endpoints include pre-dose FEV1, EXACT-PRO (EXAcerbations of Chronic pulmonary disease Tool - Patient-Reported Outcome)-defined exacerbations, St George's Respiratory Questionnaire for COPD, COPD Assessment Test, and EXACT-Respiratory Symptoms total score. Lung-specific biomarkers (surfactant protein D and CC chemokine ligand-18) will be measured in a subset of patients to explore their relationship to other clinical indices in COPD and their predictive utility. Pneumonia will be diagnosed per criteria defined by the British Thoracic Society community acquired pneumonia guideline, primarily by radiological confirmation and, additionally, using clinical criteria when a chest radiograph cannot be obtained. Serial measurements of serum potassium, vital signs and electrocardiograms, 24-hour Holter monitoring, and 24-hour urinary cortisol measurement will be performed in a subset of patients in addition to conventional safety assessments.
authors.affiliation: Department of Internal and CardioRespiratory Medicine, Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.affiliation: Institute for Infection and Immunity, St George's, University of London, London, UK.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Jones
authors.affiliation: Medical Science - Respiratory, Mundipharma Research Ltd, Cambridge, UK.
authors.forename: Prashant S
authors.initials: PS
authors.lastname: Dalvi
authors.affiliation: Medical Operations, Mundipharma Research Ltd, Cambridge, UK.
authors.forename: Kirsten
authors.initials: K
authors.lastname: McAulay
authors.affiliation: Data Management and Statistics, Mundipharma Research Ltd, Cambridge, UK.
authors.forename: Tammy
authors.initials: T
authors.lastname: McIver
authors.affiliation: Medical Science - Respiratory, Mundipharma Research Ltd, Cambridge, UK.
authors.forename: Sanjeeva
authors.initials: S
authors.lastname: Dissanayake
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D019742:Chemokines, CC / Q000097:blood*; D002985:Clinical Protocols; D018450:Disease Progression; D004311:Double-Blind Method; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*; D020127:Recovery of Function; D012107:Research Design; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D015415:Biomarkers; D001993:Bronchodilator Agents; C111792:CCL18 protein, human; D019742:Chemokines, CC; D004338:Drug Combinations; D004983:Ethanolamines; D037663:Pulmonary Surfactant-Associated Protein D; C586520:fluticasone-formoterol; D000068298:Fluticasone; D000068759:Formoterol Fumarate
keywords: chronic obstructive pulmonary disease; flutiform; inhaled corticosteroids; long-acting β2-agonist