Effect of BDP/Formoterol/G on Cough Efficacy in Moderate to Severe COPD Patients (EFFICACE)
NCT ID: NCT05114434
Last Updated: 2021-11-10
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
Total Enrollment
40 participants
Study Classification
OBSERVATIONAL
Study Start Date
2021-11-30
Study Completion Date
2023-06-30
Brief Summary
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This prospective, single centre, 8 weeks, open-label study is designed to evaluate in real-life the effect of triple Beclometasone/Formoterol/Glycopyrronium (BDP/F/G) therapy on cough efficacy, assessed by cough peak flow (CPF), after 8 weeks' treatment in patients with moderate to severe COPD.
The study's hypothesis is that in symptomatic moderate to severe COPD patients the administration of fixed dose combination BDP/F/G, by reducing lung hyperinflation (LH) and targeting small airways, may accordingly improve the cough efficacy. The increase in cough efficacy might in turn positively influence the quality of life of patients and underlie the prevention of acute exacerbations of COPD.
The study's hypothesis is that in symptomatic moderate to severe COPD patients the administration of fixed dose combination BDP/F/G, by reducing lung hyperinflation (LH) and targeting small airways, may accordingly improve the cough efficacy. The increase in cough efficacy might in turn positively influence the quality of life of patients and underlie the prevention of acute exacerbations of COPD.
Detailed Description
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The cough is a vital defensive mechanism of respiratory system. Chronic obstructive pulmonary disease (COPD) is characterised by persistent inflammation in the small airways inducing pathological changes that reduce airflow and increase gas trapping and lung hyperinflation (LH). LH in turn leads to the changes in diaphragmatic excursions: this might decrease the efficacy of cough. In moderate to severe COPD patients, the cough efficacy, expressed as cough peak flow (CPF) and cough expired volume (CEV), is significantly reduced when compared to those of controls.
A triple combination inhaler containing beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) was developed as an extrafine formulation to enable efficient delivery of an inhaled corticosteroid (ICS) combined with a long-acting beta2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA) to the small airways, improving LH and associated symptoms.
The study's hypothesis is that the administration of fixed extrafine BDP/F/G 87/5/9 µg q.d. for 8 weeks will determine an increase of CPF, CEV, lung function and quality of life in COPD patients non adequately controlled by double combination of inhaled treatment with ICS plus LABA or ICS plus LAMA or LABA plus LAMA.
CPF, CEV, residual volume (RV), inspiratory capacity (IC), total lung capacity (TLC), RV/TLC ratio, forced expiratory volume at 1st second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio will be assessed at baseline (Visit 1, V1) and after 4 weeks' treatment with BDP/F/G (Visit 2, V2). The same assessments will be performed after 4 weeks' treatment (Visit 3, V3).
The switch from the double to triple therapy will be carried out according to clinical practice and to the summary of product characteristics.
At V1, V2, and V3 dyspnoea perception, assessed by the modified Medical Research Council (mMRC) scale score and the quality of life, assessed by the COPD Assessment Test (CAT), will be recorded.
V1, V2, V3 will be performed in the morning between 8:00 and 10:00 ante meridien.
Each patient will sign an informed consent prior to initiation of any study-related procedure. The study protocol was approved by the local Hospital's Ethical Committee (approval number n. 38097; September 22, 2021) and it will be conducted according to the Good Clinical Practices and the Declaration of Helsinki.
The population will consist of 40 adult patients. Assuming a p values \< 0.05, a sample size of 40 patients (34 + 15% drop outs) is required to detect difference of 0.4 L/s (liters/second) with a standard deviation (SD) of 0.69 in CPF following a 8 weeks BDP/F/G treatment, with a power of 90%. Efficacy endpoints will be analysed using the intention to treat analysis (ITT) which will comprise all patients treated for 8 weeks with BDP/F/G 87/5/9 µg q.d. at visit 3.
Data will be collected in a dedicated electronic Clinical Records Form (CRF). The database will be saved on a password-protected company Personal Computer (PC) which will be updated at each visit and used exclusively for scientific research purposes. At the time of enrollment, each patient will receive an alphanumeric code so that any information collected during the study, and in particular sensitive data, is treated in an anonymous manner. Data reporting patients' identifications will only be used to file patients and collect informed consent.
A triple combination inhaler containing beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) was developed as an extrafine formulation to enable efficient delivery of an inhaled corticosteroid (ICS) combined with a long-acting beta2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA) to the small airways, improving LH and associated symptoms.
The study's hypothesis is that the administration of fixed extrafine BDP/F/G 87/5/9 µg q.d. for 8 weeks will determine an increase of CPF, CEV, lung function and quality of life in COPD patients non adequately controlled by double combination of inhaled treatment with ICS plus LABA or ICS plus LAMA or LABA plus LAMA.
CPF, CEV, residual volume (RV), inspiratory capacity (IC), total lung capacity (TLC), RV/TLC ratio, forced expiratory volume at 1st second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio will be assessed at baseline (Visit 1, V1) and after 4 weeks' treatment with BDP/F/G (Visit 2, V2). The same assessments will be performed after 4 weeks' treatment (Visit 3, V3).
The switch from the double to triple therapy will be carried out according to clinical practice and to the summary of product characteristics.
At V1, V2, and V3 dyspnoea perception, assessed by the modified Medical Research Council (mMRC) scale score and the quality of life, assessed by the COPD Assessment Test (CAT), will be recorded.
V1, V2, V3 will be performed in the morning between 8:00 and 10:00 ante meridien.
Each patient will sign an informed consent prior to initiation of any study-related procedure. The study protocol was approved by the local Hospital's Ethical Committee (approval number n. 38097; September 22, 2021) and it will be conducted according to the Good Clinical Practices and the Declaration of Helsinki.
The population will consist of 40 adult patients. Assuming a p values \< 0.05, a sample size of 40 patients (34 + 15% drop outs) is required to detect difference of 0.4 L/s (liters/second) with a standard deviation (SD) of 0.69 in CPF following a 8 weeks BDP/F/G treatment, with a power of 90%. Efficacy endpoints will be analysed using the intention to treat analysis (ITT) which will comprise all patients treated for 8 weeks with BDP/F/G 87/5/9 µg q.d. at visit 3.
Data will be collected in a dedicated electronic Clinical Records Form (CRF). The database will be saved on a password-protected company Personal Computer (PC) which will be updated at each visit and used exclusively for scientific research purposes. At the time of enrollment, each patient will receive an alphanumeric code so that any information collected during the study, and in particular sensitive data, is treated in an anonymous manner. Data reporting patients' identifications will only be used to file patients and collect informed consent.
Conditions
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COPD, Chronic Obstructive Pulmonary Disease
Keywords
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COPD
Beclometasone/Formoterol/Glycopyrronium (BDP/F/G)
Cough Peak Flow (CPF)
Study Design
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Observational Model Type
COHORT
Study Time Perspective
PROSPECTIVE
Eligibility Criteria
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Inclusion Criteria
* Male or female adults aged ≥40 years;
* Signed informed consent;
* Current or ex-smokers with a smoking history of at least 10 pack years. An ex smoker will be defined as a subject who has not smoked for ≥ 6months at screening;
* Diagnosis of COPD according to the International Statement;
* COPD patients with a forced expiratory volume in the 1st second (FEV1) between 30% and 80% of predicted post-bronchodilator (salbutamol 400 µg) at baseline visit;
* COPD patients with lung hyperinflation with residual volume (RV) ≥ 120% predicted;
* COPD patients treated with ICS/LABA or LABA/LAMA or ICS/LAMA therapy from at least one month before baseline visit;
* COPD patients with elevated impact of disease and/or symptoms defined by a CAT≥ 10 score and/or a mMRC ≥ 2 score and an history of exacerbation (≥ 1 exacerbation in the previous year).
* Signed informed consent;
* Current or ex-smokers with a smoking history of at least 10 pack years. An ex smoker will be defined as a subject who has not smoked for ≥ 6months at screening;
* Diagnosis of COPD according to the International Statement;
* COPD patients with a forced expiratory volume in the 1st second (FEV1) between 30% and 80% of predicted post-bronchodilator (salbutamol 400 µg) at baseline visit;
* COPD patients with lung hyperinflation with residual volume (RV) ≥ 120% predicted;
* COPD patients treated with ICS/LABA or LABA/LAMA or ICS/LAMA therapy from at least one month before baseline visit;
* COPD patients with elevated impact of disease and/or symptoms defined by a CAT≥ 10 score and/or a mMRC ≥ 2 score and an history of exacerbation (≥ 1 exacerbation in the previous year).
Exclusion Criteria
* Patients with COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 4 weeks prior to enrolment;
* Patients with concomitant other lung disease (e.g. asthma, lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension);
* Patients requiring long-term oxygen therapy (LTOT) ≥12 h a day on a daily basis for chronic hypoxemia;
* Patients with severe comorbidities associated to COPD, such as unstable cardiovascular diseases or cancer;
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment will be considered for enrolment;
* Patients with clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, myocardial infarction), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or haematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment;
* COPD patients treated with triple LABA/LAMA/ICS therapy;
* Pregnant women;
* Subjects unable to meet the criteria of acceptability and repeatability of pulmonary function tests, according to the American Thoracic Society/European Respiratory Society (ATS/ERS) document.
* Patients with concomitant other lung disease (e.g. asthma, lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension);
* Patients requiring long-term oxygen therapy (LTOT) ≥12 h a day on a daily basis for chronic hypoxemia;
* Patients with severe comorbidities associated to COPD, such as unstable cardiovascular diseases or cancer;
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment will be considered for enrolment;
* Patients with clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, myocardial infarction), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or haematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment;
* COPD patients treated with triple LABA/LAMA/ICS therapy;
* Pregnant women;
* Subjects unable to meet the criteria of acceptability and repeatability of pulmonary function tests, according to the American Thoracic Society/European Respiratory Society (ATS/ERS) document.
Minimum Eligible Age
40 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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Chiesi Farmaceutici S.p.A.
INDUSTRY
Sponsor Role
collaborator
University of Parma
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Locations
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Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Italy
Parma, , Italy
Site Status
Countries
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Italy
Central Contacts
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Facility Contacts
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Alfredo A Chetta, MD
Role: primary
Marina Aiello, MD
Role: backup
References
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Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J; Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-55. doi: 10.1164/rccm.200703-456SO. Epub 2007 May 16.
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RESULT
Dal Vecchio L, Polese G, Poggi R, Rossi A. "Intrinsic" positive end-expiratory pressure in stable patients with chronic obstructive pulmonary disease. Eur Respir J. 1990 Jan;3(1):74-80.
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RESULT
Hellebrandova L, Chlumsky J, Vostatek P, Novak D, Ryznarova Z, Bunc V. Airflow limitation is accompanied by diaphragm dysfunction. Physiol Res. 2016 Jul 18;65(3):469-79. doi: 10.33549/physiolres.933064. Epub 2016 Apr 12.
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RESULT
Smith JA, Aliverti A, Quaranta M, McGuinness K, Kelsall A, Earis J, Calverley PM. Chest wall dynamics during voluntary and induced cough in healthy volunteers. J Physiol. 2012 Feb 1;590(3):563-74. doi: 10.1113/jphysiol.2011.213157. Epub 2011 Dec 5.
Reference Type
RESULT
Sivasothy P, Brown L, Smith IE, Shneerson JM. Effect of manually assisted cough and mechanical insufflation on cough flow of normal subjects, patients with chronic obstructive pulmonary disease (COPD), and patients with respiratory muscle weakness. Thorax. 2001 Jun;56(6):438-44. doi: 10.1136/thorax.56.6.438.
Reference Type
RESULT
Dean J, Panainte C, Khan N, Singh D. The TRIFLOW study: a randomised, cross-over study evaluating the effects of extrafine beclometasone/formoterol/glycopyrronium on gas trapping in COPD. Respir Res. 2020 Dec 9;21(1):323. doi: 10.1186/s12931-020-01589-5.
Reference Type
RESULT
Singh D, Corradi M, Spinola M, Papi A, Usmani OS, Scuri M, Petruzzelli S, Vestbo J. Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide. Int J Chron Obstruct Pulmon Dis. 2017 Oct 6;12:2917-2928. doi: 10.2147/COPD.S146822. eCollection 2017.
Reference Type
RESULT
French CL, Irwin RS, Curley FJ, Krikorian CJ. Impact of chronic cough on quality of life. Arch Intern Med. 1998 Aug 10-24;158(15):1657-61. doi: 10.1001/archinte.158.15.1657.
Reference Type
RESULT
Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.
Reference Type
RESULT
Rogliani P, Matera MG, Facciolo F, Page C, Cazzola M, Calzetta L. Beclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide: Synergy of triple combination therapy on human airway smooth muscle ex vivo. Br J Pharmacol. 2020 Mar;177(5):1150-1163. doi: 10.1111/bph.14909. Epub 2020 Jan 29.
Reference Type
RESULT
Calzetta L, Cazzola M, Matera MG, Rogliani P. Adding a LAMA to ICS/LABA Therapy: A Meta-analysis of Triple Combination Therapy in COPD. Chest. 2019 Apr;155(4):758-770. doi: 10.1016/j.chest.2018.12.016. Epub 2019 Jan 17.
Reference Type
RESULT
Cazzola M, Di Marco F, Santus P, Boveri B, Verga M, Matera MG, Centanni S. The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD. Pulm Pharmacol Ther. 2004;17(1):35-9. doi: 10.1016/j.pupt.2003.09.001.
Reference Type
RESULT
Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999 Jul;54(7):581-6. doi: 10.1136/thx.54.7.581.
Reference Type
RESULT
Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509.
Reference Type
RESULT
Other Identifiers
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38097
Identifier Type: -
Identifier Source: org_study_id