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

• ClinicalTrials.gov Identifier: NCT03846570
• Recruitment Status: Unknown
• First Posted: February 19, 2019
• Last Update Posted: February 22, 2019
• Sponsor: Erasmus Medical Center
• Collaborator: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): Menno M. van der Eerden, Erasmus Medical Center

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 (Clinical Trial)
• Estimated 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: January 29, 2019
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

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

Outcome Measures

Primary Outcome Measures :

1. Clinical effect on coughing [ Time Frame: 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 :

1. Quality of life in patient with bronchiectasis [ Time Frame: 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.

2. Pulmonary function [ Time Frame: 3 months ]
   Spirometry: FEV1
3. Exacerbation frequency [ Time Frame: 3 months ]
   The frequency of exacerbation requiring an intervention with systemic antibiotics (oral/intravenous [i.v.])
4. Sputum production [ Time Frame: 3 months ]
   in mL
5. Dyspnea score [ Time Frame: 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'.

6. Incidence of Adverse Events [Safety and Tolerability]). [ Time Frame: 3 months ]
   Incidence of Adverse Events [Safety and Tolerability]).
7. Sputum culture [ Time Frame: 3 months ]
   Micro organisms isolated during study

Other Outcome Measures:

1. Inflammatory response in serum: C-reactive protein [ Time Frame: 3 months ]
   Measuring high-sensitivity C-reactive protein (mg/L) at baseline and 3 months
2. Inflammatory response in serum: erythrocyte sedimentation rate [ Time Frame: 3 months ]
   Measuring the erythrocyte sedimentation rate (mm/h) at baseline and 3 months
3. Inflammatory response in serum: WBC [ Time Frame: 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
4. Inflammatory response in serum: pulmonary type 2 innate lymphoid cells [ Time Frame: 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
5. Inflammatory response in sputum [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Margot JM de Koning Gans; +31107030323; J.dekoninggans@erasmusmc.nl

Contact: Menno M Van der Eerden; +31107030323; m.vandereerden@erasmusmc.nl

Locations

Netherlands

ErasmusMC; Recruiting

Rotterdam, Netherlands

Contact: Margot JM de Koning Gans +31107030323 J.dekoninggans@erasmusmc.nl

Sponsors and Collaborators

Erasmus Medical Center

Chiesi Farmaceutici S.p.A.

Investigators

• Principal Investigator: Menno M Van der Eerden; Erasmus Medical Center

More Information

• Responsible Party: Menno M. van der Eerden, Pulmonary physician, MD, PhD, Erasmus Medical Center
• ClinicalTrials.gov Identifier: NCT03846570
• Other Study ID Numbers: NL61630.078.18
• First Posted: February 19, 2019
• Last Update Posted: February 22, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Menno M. van der Eerden, Erasmus Medical Center:

Randomized Controlled Trial; Inhaled corticosteroids; Placebo; Cough

Additional relevant MeSH terms:

Bronchiectasis; Bronchial Diseases; Respiratory Tract Diseases; Beclomethasone; Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists