Brief Title
Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Bronchiectasis
Official Title
Effect of Roflumilast on Quality of Life, Lung Function and Mucus Properties in Patients With Non-cystic Fibrosis Bronchiectasis: a Cross-over, Unicentric, Double-blind and Placebo-controlled Study
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Quality of life questionnaire
Secondary Outcome
Other tools for quality of life
Condition
Bronchiectasis Adult
Intervention
Roflumilast
Study Arms / Comparison Groups
Roflumilast
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
December 6, 2019
Completion Date
December 2020
Primary Completion Date
December 2020
Eligibility Criteria
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).
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Rodrigo A Athanazio, MD, PhD, +55 11 2661-5000, [email protected]
Location Countries
Brazil
Location Countries
Brazil
Administrative Informations
NCT ID
NCT03988816
Organization ID
SDC 4706/18/057
Secondary IDs
2018/17035-5
Responsible Party
Sponsor
Study Sponsor
University of Sao Paulo General Hospital
Collaborators
FAPESP - Fundação de Apoio à Pesquisa do Estado de São Paulo
Study Sponsor
Rodrigo A Athanazio, MD, PhD, Principal Investigator, Medical Assistant
Verification Date
June 2019