The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and SAD in COPD Patients.

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

The Effect of Beclomethasone/Formoterol in Extra-fine Formulation on Quality of Life and Dyspnea is Associated to the Improvement in Small Airway Dysfunction in COPD Patients. A Pilot Study (IOSCOPD20161102)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04421742
• Other study ID #: 9769 del 15.03.2017
• Status: Completed
• Start date: May 31, 2017
• Est. completion date: May 23, 2019

Study information

• Verified date: June 2020
• Source: University of Parma
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In patients with chronic obstructive pulmonary disease (COPD), small-airway dysfunction (SAD) is considered a key element and a functional consequence of the pathology. However, the exact role of SAD as a specific 'pharmacological target' is not yet fully known.

Objectives In an open-label prospective study, we aimed to ascertain whether an extra-fine formulation of Beclomethasone dipropionate/Formoterol fumarate (BDP/FF) NEXThaler® 100/6 μg b.i.d. can improve the impact of the disease on the quality of daily life of COPD patients, acting on SAD.

Methods We studied COPD patients with severe airflow obstruction and 1 moderate exacerbation in the previous year, being treated with BDP/FF NEXThaler® for 12 weeks. They underwent three visits, at the start of the treatment (V1), at 6th week (V2) and at 12th week (V3). By the impulse oscillometry system and by spirometry and plethysmography we measured at each visit the fall in resistance from 5 to 20 Hz (R5-R20) and the residual volume/total lung capacity (RV/TLC). COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) questionnaire were also measured at each visit to assess the impact of the disease on the quality of life of the patients.

Description:

In recent years, there has been a growing interest in deepening the contribution of small airways (with a diameter <2mm) to the clinical expression of Chronic Obstructive Pulmonary Disease (COPD).

In patients with stable COPD, SAD severity was found to be progressively increased both with the degree of airflow obstruction and with GOLD risk class. Moreover, a correlation between SAD and COPD impact measured with the CAT (COPD Assessment Test) was found, being the severity of SAD a predictor of the impact of the disease (CAT≥10). A close correlation between SAD and both quality of life (measured with the St. George's Respiratory Questionnaire) and perceived dyspnea (measured with the modified Medical Research Council-mMRC scale) was also found in COPD patients.

The exact role of SAD as a specific 'pharmacological target' is not yet fully known. According to the guidelines, the administration of combination such as Beclomethasone dipropionate/Formoterol fumarate (BDP/FF) in extra-fine formulation produced a clinically relevant improvement in quality of life (> 4 units in the St. George's Respiratory Questionnaire) and in dyspnea. However, it is not yet defined whether exists a correlation between symptomatic improvement and SAD and whether an improvement of symptoms can be achieved acting pharmacologically on SAD.

The rationale for this study is based on the hypothesis that an extra-fine formulation of BDP/FF, designed to target the entire bronchial three, included the peripheral zone, can improve the impact of the disease on the quality of life of COPD patients, acting on SAD. The functional indices of SAD used in this study are from the impulse oscillometry system (IOS), the standard spirometry and the body plethysmography.

The primary endpoint of the study was, therefore, an improvement of the impact of the disease on quality of daily life (CAT) and of dyspnea (mMRC) after 12th week treatment with an extra-fine formulation of BDP/FF in a cohort of COPD patients with severe airway obstruction and one moderate exacerbation in a previous year; secondary endpoint was an improvement of the SAD at the 12th week in these patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: May 23, 2019
• Est. primary completion date: February 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• a documented diagnosis of COPD defined according to the guidelines of the American Thoracic Society (ATS) / European Respiratory Society (ERS);

• smokers or former smokers with a smoking history of at least 10 pack / years;

• subjects with a post-bronchodilator forced expiratory volume at the 1st second (FEV1)/ forced vital capacity (FVC) ratio of < 0.7 and a FEV1 <50% pred;

• subjects with a high impact of the COPD on their health status (CAT=10);

• clinical history of at least 1 moderate exacerbation / year;

• COPD patients being treated with BDP/FF NEXThaler® 100/6 µg in extra-fine formulation no more than 1 (one) week before enrollment.

Exclusion Criteria:

• an exacerbation in the four weeks prior to enrollment;

• other coexisting lung diseases (bronchial asthma, restrictive diseases or bronchiectasis) and severe co-morbidities associated with COPD, such as uncontrolled cardiovascular disease, pneumonia or cancer;

• pregnant patients;

• subjects unable to meet the criteria of acceptability and repeatability of pulmonary function tests, according to the ATS / ERS document

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Beclomethasone Dipropionate/Formoterol Fumarate
BDP/FF NEXThaler® 100/6 µg b.i.d.

Locations

Country	Name	City	State
Italy	Department of Medicine and Surgery, Respiratory Disease and Lung Function Unit, University of Parma, Italy	Parma

Sponsors (2)

Lead Sponsor	Collaborator
Alfredo Antonio Chetta	University of Parma

Country where clinical trial is conducted

Italy, 

References & Publications (17)

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Crisafulli E, Pisi R, Aiello M, Vigna M, Tzani P, Torres A, Bertorelli G, Chetta A. Prevalence of Small-Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the Impact of Disease. Respiration. 2017;93(1):32-41. Epub 2016 Nov 1 — View Citation

De Backer W, Devolder A, Poli G, Acerbi D, Monno R, Herpich C, Sommerer K, Meyer T, Mariotti F. Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients. J Aerosol Med Pulm Drug Deliv. 2010 Jun;23(3):137-48. doi: 10.1 — View Citation

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Oostveen E, MacLeod D, Lorino H, Farré R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 — View Citation

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* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change (Improvement) of CAT (Italian version)	The CAT (COPD Assessment Test) is a questionnaire suitable for completion by all patients diagnosed with COPD. It comprises 8 simple questions that most patients should be able to understand and complete independently.; The CAT has a scoring range of 0-40, where each question is ranging 0-5. A CAT score>10 indicates a medium/high impact level of COPD.; A difference or change of 2 or more units over 2 to 3 months in a patient suggests a clinically significant difference or change in health status (minimal clinically relevant change, often referred to as the Minimum Clinically Important Difference or MCID).	Change from Baseline CAT at 12th week
Primary	Change (Improvement) of mMRC (Italian version)	The modified Medical Research Council (mMRC) dyspnoea scale is a questionnaire that consists of five statements about perceived breathlessness: grade 1, "I only get breathless with strenuous exercise"; grade 2, "I get short of breath when hurrying on the level or up a slight hill"; grade 3, "I walk slower than people of the same age on the level because of breathlessness or have to stop for breath when walking at my own pace on the level"; grade 4, "I stop for breath after walking 100 yards or after a few minutes on the level"; grade 5, " I am too breathless to leave the house". Patients are asked about their perceived breathlessness and are then classified into MRC dyspnoea grades according to how they perceive their disability.	Change from Baseline mMRC at 12th week
Primary	Change (Improvement) of R5-R20 (kPa x s x L-1)	The IOS was performed with the Jaeger MasterScreen-IOS device following the standard recommendations. Respiratory resistances at 5 Hz and 20 Hz (R5 and R20, kPa x s x L-1) were used as a total and proximal airway resistance index, respectively, and the resistance drop from 5 to 20 Hz (R5 - R20, kPa x s x L-1) was considered as an indirect index of resistance of the peripheral airways. The oscillometer was calibrated daily.	Change from Baseline R5-R20 at 12th week

External Links

•   CAT Development Steering Group: COPD Assessment Test - Healthcare Professional User Guide. Issue 4: November 2018.
•   Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018