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

Sponsor

Erasmus Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03846570

Collaborator

Chiesi Farmaceutici S.p.A. (Industry)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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)

Condition or Disease	Intervention/Treatment	Phase
Bronchiectasis	Drug: Formoterol-beclomethasone Drug: Placebo	Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 29, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Formoterol-beclomethasone

Formoterol (fumarate dehydrate) 12 microg - beclomethasone (dipropionate) 200 microg administered BID, per inhalation using '100/6' Metered Dose Inhaler.

Drug: Formoterol-beclomethasone

formoterol (fumarate dihydrate) 12 microg - beclomethasone (dipropionate) 200 microg administered BID, per inhalation using '100/6' Metered Dose Inhaler

Placebo Comparator: Placebo

Matching placebo (identically package) administered BID

Drug: Placebo

Matching placebo (identically package) administered BID

Outcome Measures

Primary Outcome Measures

Clinical effect on coughing [3 months]
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.)

Secondary Outcome Measures

Quality of life in patient with bronchiectasis [3 months]
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.
Pulmonary function [3 months]
Spirometry: FEV1
Exacerbation frequency [3 months]
The frequency of exacerbation requiring an intervention with systemic antibiotics (oral/intravenous [i.v.])
Sputum production [3 months]
in mL
Dyspnea score [3 months]
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'.
Incidence of Adverse Events [Safety and Tolerability]). [3 months]
Incidence of Adverse Events [Safety and Tolerability]).
Sputum culture [3 months]
Micro organisms isolated during study

Other Outcome Measures

Inflammatory response in serum: C-reactive protein [3 months]
Measuring high-sensitivity C-reactive protein (mg/L) at baseline and 3 months
Inflammatory response in serum: erythrocyte sedimentation rate [3 months]
Measuring the erythrocyte sedimentation rate (mm/h) at baseline and 3 months
Inflammatory response in serum: WBC [3 months]
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
Inflammatory response in serum: pulmonary type 2 innate lymphoid cells [3 months]
Measuring pulmonary type 2 innate lymphoid cells including IL-4, IL-5 and IL-13 (all in pg/ml) at baseline and 3 months
Inflammatory response in sputum [3 months]
Measuring the numbers of pulmonary type 2 innate lymphoid cells (ILC2) per ml sputum, observing any change from baseline to 3 months.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.