Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Bronchiectasis

Phase 2

• Conditions: Bronchiectasis Adult
• Interventions: Drug: Roflumilast; Drug: Placebo oral tablet

• Registration Number: NCT03988816
• Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary

Although relatively common, bronchiectasis is considered an orphan disease as there is little evidence for adequate treatment, most of the therapeutic options are extrapolated from studies with patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Inhaled bronchodilators and corticosteroids should be used as a therapeutic test and maintained if there is improvement of symptoms or lung function. There is no evidence to justify the use of mucolytic agents for these patients. The treatment with greater evidence is the use of macrolides, especially azithromycin. A meta-analysis published in 2014 showed that there was a reduction in the number of exacerbations, an improvement in the quality of life and a reduction in the decrease in FEV1. However, studies have shown conflicting results regarding quality of life and pulmonary function.

Roflumilast is a phosphodiesterase-4 inhibitor with an anti-inflammatory effect in vitro and in vivo due to the inhibition of cyclic adenosine monopostat breakdown (cAMP) to its inactive phosphodiesterase form. As this enzyme is expressed in high concentrations in leukocytes and other inflammatory cells responsible for the pathogenesis of pulmonary diseases such as COPD, it has been studied and used for this disease. COPD is characterized by a chronic inflammatory process of the airways, predominantly neutrophils and high levels of proinflammatory cytokines related to this cell, such as interleukin-8, neutrophil elastase, tumor necrosis factor (TNF) alpha and E-selectin. The REACT study showed that roflumilast prevents moderate and severe infectious exacerbations in addition to improved lung function in patients with COPD who continue to exacerbate despite the use of combined bronchodilator and inhaled corticosteroid therapy.

Since bronchiectasis and COPD are chronic inflammatory diseases, they present similar inflammatory processes, with neutrophil as the main inflammatory cell, it is expected that the use of roflumilast also has an anti-inflammatory effect in bronchiectasis. In addition, since bronchiectasis is a disease with poor evidence for pharmacological treatment, it is necessary to search for new therapeutic possibilities.

Detailed Description

Not available

Study Timeline

• Status Verified: 2019-06
• Study First Submitted: 2019-06-14
• Study First Submitted QC: 2019-06-14
• Study First Posted: 2019-06-17
• Study Start: 2019-12-06
• Last Update Submitted: 2020-01-07
• Last Update Posted: 2020-01-13
• Primary Completion: 2020-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Age > 18 years;
• Diagnosis of bronchiectasis by chest tomography;
• FEV1 <60% of predicted;
• History of chronic bronchitis (chronic cough and sputum for at least 3 months in the last 2 years);
• 2 or more infectious exacerbations in the last year (defined as worsening of cough and / or dyspnoea and / or decreased general condition, increased quantity and purulence of sputum that required systemic antibiotic use (oral or intravenous).

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Exclusion Criteria

• Hemoptysis in the last 6 months (significance at the discretion of the investigator);
• Current or prior smoking if > 10 pack-years;
• FEV1 < 30% of predicted;
• Known allergy to roflumilast;
• Pulmonary exacerbation present or occurring in the last 4 weeks;
• Child B or C cirrhosis;
• Active cancer (except basal cell carcinoma);
• Severe heart failure;
• Depression associated with suicidal ideation;
• Pregnancy.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Roflumilast	Roflumilast	Roflumilast tablets will be supplied at a concentration of 500 mcg. Each tablet contains 500mcg of the active ingredient in addition to the excipients: lactose monohydrate, corn starch, povidone and magnesium stearate. The coating contains hypromellose, macrogol, titanium dioxide, yellow iron oxide. Patients should take 1 tablet once daily, before, during or after meals, at the same time each day.
Placebo (control)	Placebo oral tablet	Roflumilast placebo-containing tablets will look similar to active roflumilast tablets and will be supplied to patients in packs identical to those of the active drug.

Primary Outcome Measures

Name	Time	Method
Quality of life questionnaire	12 weeks	To evaluate the impact of roflumilast on the quality of life of patients with bronchiectasis through the Saint George Respiratory Questionnaire (SGRQ).

Secondary Outcome Measures

Name	Time	Method
Dyspnea	12 weeks	To evaluate the impact of roflumilast on severity of dyspnea as measured by the COPD Assessment Test (CAT)
Lung function	12 weeks	To evaluate the impact of roflumilast on lung function measured by forced expiratory volume at one second (FEV1)
Adverse events	12 weeks	To evaluate the safety of roflumilast assessed through the incidence of adverse events
Other tools for quality of life	12 weeks	To evaluate the impact of roflumilast on quality of life using the questionnaires Leicester, Quality of Life Questionnaire-Bronchiectasis (QOL-B) Bronchiectasis Health Questionnaire (BHQ)

Trial Locations

Locations (1)

Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; 🇧🇷 São Paulo, SP, Brazil