Condition category
Respiratory
Date applied
17/09/2020
Date assigned
22/09/2020
Last edited
21/09/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation caused by abnormalities in the lungs due to exposure to particulate matter or gas. Treatment with inhaled corticosteroids (ICS) in combination with long-acting bronchodilators (to open the air passages in the lungs) is more effective than the individual components in improving lung function, symptoms, and exacerbations. Usually, a triple combination with one ICS plus two long-acting bronchodilators are administered at severe COPD patients. Adding a short-acting bronchodilator (i.e. salbutamol) in addition to basic inhalation therapy with long-acting bronchodilators may further improve the level of bronchodilation. The aim of this study was to assess whether triple combination therapy may lead to maximal bronchorelaxant effect in the airways of COPD patients.

Who can participate?
Severe COPD patients were enrolled in the study.

What does the study involve?
Patients were treated for 15 days with triple combination therapy, and generally they were assessed for lung function, symptoms, and routine procedures.

What are the possible benefits and risks of participating?
These patients had the benefit to be treated with the most effective therapy for severe COPD, the so-called triple combination therapy. The risks were the potential adverse events already known for the triple combination therapy used in this study and already approved in the market, named Trimbow®.

Where is the study run from?
The study was run at the University Hospital of Rome "Tor Vergata", Italy,

When is the study starting and how long is it expected to run for?
January 2019 to September 2020

Who is funding the study?
The University Hospital of Rome "Tor Vergata" (Italy)

Who is the main contact?
Prof. Paola Rogliani
paola.rogliani@uniroma2.it

Trial website

Contact information

Type

Scientific

Primary contact

Prof Paola Rogliani

ORCID ID

Contact details

Via Montpellier
1
Rome
00133
Italy
+39 (0)6 2090 4656
paola.rogliani@uniroma2.it

Type

Scientific

Additional contact

Dr Luigino Calzetta

ORCID ID

Contact details

Via Montpellier
1
Rome
00133
Italy
+39 (0)6 76259 6666
luigino.calzetta@unipr.it

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

252/19

Study information

Scientific title

Ceiling effect of triple beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide combination in COPD: a translational bench-to-bedside study

Acronym

Study hypothesis

The aim of this study is to assess residual bronchodilation in patients suffering from chronic obstructive pulmonary disease (COPD) after administration of the beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) triple combination. BDP/FF/GB is a fixed-dose combination (FDC) of a long-acting muscarinic antagonist (LAMA), a long-acting β2 adrenoceptor agonist (LABA) and an inhaled corticosteroid (ICS) already approved as chronic therapy by EMA and AIFA for COPD patients with two moderate exacerbations per year or one severe and symptomatic exacerbation. According to the current GOLD recommendations, the COPD patient in chronic therapy with bronchodilators can use, if needed, therapy with short-acting bronchodilators such as salbutamol. However, to date, it is not known whether the "add-on" therapy of a short-acting bronchodilator such as salbutamol may result in an improvement in lung function in COPD patients already on BDP/FF/GB therapy.

Overall, this study investigates whether BDP/FF/GB may lead to ceiling bronchorelaxant effect in the airways of COPD patients, and whether there may be some different effect at the level of medium bronchi and small airways.

Ethics approval

Approved 26/02/2020, Local institutional ethics committee CEI (Comitato Etico Indipendente, Rome “Tor Vergata”, Viale Oxford, 81 - 00133 Roma, Italy; +39 06 2090 0035; no email provided), ref: RS 252/19, 2020

Study design

Pilot single-arm open-label prospective observational single-centre study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic obstructive pulmonary disease (COPD)

Intervention

Pulmonary function test (PFT) and impulse oscillometry (IOS) are performed at baseline before and during dose-response curve (DRC) to salbutamol (100 μg, 200 μg, 400 μg, 800 μg). After that, patients are treated with Trimbow®, an extrafine formulation of BDP, FF, and GP (BDP/FF/GB 100/6/12.5 μg) administered BID as FDC. At day 14 the DRC to salbutamol is performed on top of the peak effect induced by BDP/FF/GB 100/6/12.5 μg FDC (2 h after the last inhalation of the FDC), along with PFT and IOS. At day 15 (visit 4) the DRC to salbutamol is performed on top of the trough effect induced by BDP/FF/GB 100/6/12.5 μg FDC (11 h after the last inhalation of the triple combination therapy), along with PFT and IOS.

Intervention type

Drug

Phase

Not Applicable

Drug names

1. Beclomethasone dipropionate
2. Formoterol fumarate
3. Glycopyrronium bromide
4. Salbutamol

Primary outcome measure

Bronchorelaxant effect at the level of small airways (airway resistance) measured using impulse oscillometry at baseline (day 1), day 14 and day 15

Secondary outcome measures

1. Bronchorelaxant effect at the level of medium bronchi measured using forced expiratory volume in 1 s [FEV1] at baseline (day 1), day 14 and day 15
2. Dyspnea using Modified British Medical Research Council Questionnaire ( mMRC) and Visual Analogue Scale (VAS) at baseline (day 1), day 14 and day 15
3. Oxygen saturation (SpO2) and heart rate (HR) using pulse oximetry at baseline (day 1), day 14 and day 15

Overall trial start date

10/01/2019

Overall trial end date

01/09/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. COPD patients ≥40 years old
2. Current or former smokers, with a cigarette smoking history of ≥10 pack-years
3. Confirmed diagnosis of COPD (FEV1/forced vital capacity (FVC) <0.7) FEV1 <65% predicted, history of ≥1 severe exacerbation of COPD in the last year

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

16

Total final enrolment

16

Participant exclusion criteria

1. Patients with history of asthma
2. Reversibility of FEV1 by >200 ml and/or >12% after inhalation of 200 μg salbutamol
3. Under treatment with ICS

Recruitment start date

27/02/2020

Recruitment end date

30/07/2020

Locations

Countries of recruitment

Italy

Trial participating centre

University of Rome "Tor Vergata"
00133
Italy

Sponsor information

Organisation

University of Rome Tor Vergata

Sponsor details

Via Montpellier
1
Rome
00133
Italy
+39 (0)6 7259 3099
medicina.sperimentale@uniroma2.it

Sponsor type

University/education

Website

http://web.uniroma2.it/home.php?newlang=italian

Funders

Funder type

University/education

Funder name

Università degli Studi di Roma Tor Vergata

Alternative name(s)

University of Rome Tor Vergata

Funding Body Type

private sector organisation

Funding Body Subtype

Universities (academic only)

Location

Italy

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal

IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Investigator: Paola Rogliani paola.rogliani@uniroma2.it
Type of data: patient-level data, available in about 6 months for about 12 months
Data will be available on request by providing anonymized excel files.
Data will be available only for reasonable scientific research and shared with scientific institutions, only after approval by the local Ethics Committee.

Intention to publish date

01/04/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

21/09/2020: Trial’s existence confirmed by Comitato Etico Indipendente, Rome “Tor Vergata”