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

Sponsor
University of Sao Paulo General Hospital (Other)
Overall Status
Unknown status
CT.gov ID
NCT03988816
Collaborator
Fundação de Amparo à Pesquisa do Estado de São Paulo (Other)
30
Enrollment
1
Location
2
Arms
11.9
Anticipated Duration (Months)
2.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Placebo-controlled
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 6, 2019
Anticipated Primary Completion Date :
Dec 1, 2020
Anticipated Study Completion Date :
Dec 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Roflumilast
500Mcg Tab, once daily
Other Names:
  • Daxas

    		•
    Placebo Comparator: Placebo (control)

    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.

    Drug: Placebo oral tablet
    once daily
    Other Names:
  • Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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)

    2. Dyspnea [12 weeks]

      To evaluate the impact of roflumilast on severity of dyspnea as measured by the COPD Assessment Test (CAT)

    3. Lung function [12 weeks]

      To evaluate the impact of roflumilast on lung function measured by forced expiratory volume at one second (FEV1)

    4. Adverse events [12 weeks]

      To evaluate the safety of roflumilast assessed through the incidence of adverse events

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo São Paulo SP Brazil 05403-900

    Sponsors and Collaborators

    • University of Sao Paulo General Hospital
    • Fundação de Amparo à Pesquisa do Estado de São Paulo

    Investigators

    • Principal Investigator: Rodrigo A Athanazio, MD, PhD, Medical Assistant

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of Sao Paulo General Hospital
    ClinicalTrials.gov Identifier:
    NCT03988816
    Other Study ID Numbers:
    • SDC 4706/18/057
    • 2018/17035-5
    First Posted:
    Jun 17, 2019
    Last Update Posted:
    Jan 13, 2020
    Last Verified:
    Jun 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University of Sao Paulo General Hospital
    bronchiectasis
    lung function
    quality of life
    mucus properties
    Additional relevant MeSH terms:
    Bronchiectasis

    Study Results

    No Results Posted as of Jan 13, 2020