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

Bronchiectasis Adult Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03988816
• Other study ID #: SDC 4706/18/057
• Secondary ID: 2018/17035-5
• Status: Recruiting
• Phase: Phase 2
• Start date: December 6, 2019
• Est. completion date: December 2020

Study information

• Verified date: June 2019
• Source: University of Sao Paulo General Hospital
• Contact: Rodrigo A Athanazio, MD, PhD
• Phone: +55 11 2661-5000
• Email: rathanazio[@]yahoo.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2020
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiectasis
• Bronchiectasis Adult

Intervention

Drug:
• Roflumilast
500Mcg Tab, once daily
• Placebo oral tablet
once daily

Locations

Country	Name	City	State
Brazil	Heart Institute (InCor) - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	São Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	FAPESP - Fundação de Apoio à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (5)

Beghè B, Rabe KF, Fabbri LM. Phosphodiesterase-4 inhibitor therapy for lung diseases. Am J Respir Crit Care Med. 2013 Aug 1;188(3):271-8. doi: 10.1164/rccm.201301-0021PP. Review. — View Citation

Fjaellegaard K, Sin MD, Browatzki A, Ulrik CS. Antibiotic therapy for stable non-CF bronchiectasis in adults - A systematic review. Chron Respir Dis. 2017 May;14(2):174-186. doi: 10.1177/1479972316661923. Epub 2016 Aug 9. Review. — View Citation

Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbröker D, Bethke TD, Hiemstra PS, Rabe KF. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 Dec;62(12):1081-7. Epub 2007 Jun 15. — View Citation

McShane PJ, Naureckas ET, Tino G, Strek ME. Non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2013 Sep 15;188(6):647-56. doi: 10.1164/rccm.201303-0411CI. Review. — View Citation

Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, Smeeth L, Brown JS. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J. 2016 Jan;47(1):186-93. doi: 10.1183/13993003.01033-2015. Epub 2015 Nov 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of life questionnaire	To evaluate the impact of roflumilast on the quality of life of patients with bronchiectasis through the Saint George Respiratory Questionnaire (SGRQ).	12 weeks
Secondary	Other tools for quality of life	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)	12 weeks
Secondary	Dyspnea	To evaluate the impact of roflumilast on severity of dyspnea as measured by the COPD Assessment Test (CAT)	12 weeks
Secondary	Lung function	To evaluate the impact of roflumilast on lung function measured by forced expiratory volume at one second (FEV1)	12 weeks
Secondary	Adverse events	To evaluate the safety of roflumilast assessed through the incidence of adverse events	12 weeks