Formoterol-beclomethasone in Patients With Bronchiectasis: a Randomized Controlled Trial

Bronchiectasis Clinical Trial

— FORZA  

Official title:

Formoterol-beclomethasone in Patients With Bronchiectasis: a Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03846570
• Other study ID #: NL61630.078.18
• Status: Terminated
• Phase: Phase 3
• Start date: January 29, 2019
• Est. completion date: July 5, 2022

Study information

• Verified date: February 2023
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, double-blind, placebo-controlled study comparing formoterol-beclometason 12/200 mcg BID versus placebo to evaluate the clinical effect on coughing in patients with non-cystic fibrosis (non-CF) bronchiectasis, native to inhaled corticosteroid (ICS) therapy and no history of asthma or chronic obstructive pulmonary disease (COPD)

Description:

In the management of non-CF bronchiectasis, bronchodilator treatment (LABA)and use of inhaled corticosteroids (ICS) is still a matter of debate. Previous studies have claimed beneficial effects of ICS (with or without bronchodilator), such as improvement of the HRQL, a reduction in daily sputum volume and/or exacerbation frequency. However, in all previous studies there was no clear exclusion of patients with asthma or COPD, or no use of placebo. The current study will be the first study evaluating the effect of ICS/LABA treatment in non-CF bronchiectasis excluding patients with asthma and COPD. This is a prospective double-blind randomized controlled trial comparing Formoterol-beclomethasone 12/200 mcg BID versus placebo to evaluate the reduction in cough measured by the Leicester cough questionnaire. Secondary objectives are the improvement of health-related quality of life and symptoms, reduction in sputum production, pulmonary function (FEV1) and the frequency of exacerbation. Furthemore, we will assess the inflammatory response in serum and sputum. After a wash-out period of 1 month, eligible subjects will be randomized to treatment with formoterol-beclomethasone or matching placebo. All subjects will be treated with the regimen of medication for 3 months. An end-of-study (EOS) visit will be performed after completion of the follow-up period.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: July 5, 2022
• Est. primary completion date: July 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Symptomatic patient (wheezing, cough and dyspnoea);
• Proven and documented diagnosis of BE by high resolution computed tomography ;
• Stable pulmonary status as indicated by FEV1 (percent of predicted) =30%
• Stable clinically phase (ie, subjects free from acute exacerbation for at least 6 weeks prior to the start of the study);
• Stable regimen of standard treatment as chronic treatment for BE, at least for the past 4 weeks prior to screening. And/or macrolides if used as chronic treatment for BE at least for the past 6 months prior to screening;
• Coughing on the majority of days for more than 8 weeks;
• Ability to follow the inhaler device instructions;
• Ability to complete questionnaires;
• Written informed consent.

Exclusion Criteria:

• Possible asthma according to the definition of the Global Initiative for Asthma (GINA);
• Positive histamine provocation test
• Known intolerance for ICS or LABA;
• Women who are pregnant, lactating, or in whom pregnancy cannot be excluded;
• Expected to die within 72 hours after enrolment;
• Cigarette smoking history of > 10 pack-years or current smokers;
• Other cardiopulmonary conditions (other than bronchiectasis) that could modify spirometric values.

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• Formoterol-beclomethasone
formoterol (fumarate dihydrate) 12 microg - beclomethasone (dipropionate) 200 microg administered BID, per inhalation using '100/6' Metered Dose Inhaler
• Placebo
Matching placebo (identically package) administered BID

Locations

Country	Name	City	State
Netherlands	HagaZiekenhuis	Den Haag
Netherlands	Franciscus Gasthuis & Vlietland	Rotterdam
Netherlands	Tjeerd van der Veer	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	Chiesi Farmaceutici S.p.A.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Inflammatory response in serum: C-reactive protein	Measuring high-sensitivity C-reactive protein (mg/L) at baseline and 3 months	3 months
Other	Inflammatory response in serum: erythrocyte sedimentation rate	Measuring the erythrocyte sedimentation rate (mm/h) at baseline and 3 months	3 months
Other	Inflammatory response in serum: WBC	Measuring the white blood cell (WBC) count including polymorphonuclear leukocytes (10^9/L), neutrophils (10^9/L) and eosinophils (10^9/L) at baseline and 3 months	3 months
Other	Inflammatory response in serum: pulmonary type 2 innate lymphoid cells	Measuring pulmonary type 2 innate lymphoid cells including IL-4, IL-5 and IL-13 (all in pg/ml) at baseline and 3 months	3 months
Other	Inflammatory response in sputum	Measuring the numbers of pulmonary type 2 innate lymphoid cells (ILC2) per ml sputum, observing any change from baseline to 3 months.	3 months
Primary	Clinical effect on coughing	Using the Leicester Cough Questionnaire (LCQ) at baseline and 3 months. The LCQ is a valid, repeatable 19 item self-completed quality of life measure of chronic cough which is responsive to change. Score range: 19-133 (Higher values represent a better outcome.)	3 months
Secondary	Quality of life in patient with bronchiectasis	Mean Change From Baseline in Patient Reported Outcome Quality of Life Questionnaire for Bronchiectasis (QoL-B) Respiratory Symptoms Domain Score (measured at baseline and 3 months).; The QoL-B was a disease-specific questionnaire developed for non-Cystic fibrosis Bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension was scored separately on a scale of 0 to 100, and higher scores represent better outcomes. For this outcome measure, the respiratory symptoms domain score was reported.	3 months
Secondary	Pulmonary function	Spirometry: FEV1	3 months
Secondary	Exacerbation frequency	The frequency of exacerbation requiring an intervention with systemic antibiotics (oral/intravenous [i.v.])	3 months
Secondary	Sputum production	in mL	3 months
Secondary	Dyspnea score	mMRC (Modified Medical Research Council) Dyspnea Scale. This stratifies severity of dyspnea in respiratory diseases.; Grading from 0 to 4, respectively from 'no dyspnea' to 'very severe dyspnea'.	3 months
Secondary	Incidence of Adverse Events [Safety and Tolerability]).	Incidence of Adverse Events [Safety and Tolerability]).	3 months
Secondary	Sputum culture	Micro organisms isolated during study	3 months